To see the other types of publications on this topic, follow the link: Adenoviral.
Journal articles on the topic 'Adenoviral'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Adenoviral.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Asaoka, Katsuyuki, Mitsuhiro Tada, Yutaka Sawamura, Jun Ikeda, and Hiroshi Abe. "Dependence of efficient adenoviral gene delivery in malignant glioma cells on the expression levels of the Coxsackievirus and adenovirus receptor." Journal of Neurosurgery 92, no. 6 (June 2000): 1002–8. http://dx.doi.org/10.3171/jns.2000.92.6.1002.
Full textAbstract:
Object. Recombinant adenovirus is used as a competent vector in a wide spectrum of cancer gene therapies because of its high efficiency in gene delivery. To study the feasibility of gene therapy in malignant gliomas, the authors examined the antiproliferative effect of the adenovirally transduced wild-type p53 tumor suppressor gene by using 15 different high-grade glioma cell lines.Methods. Although growth suppression in association with a high adenoviral p53 transduction efficiency was seen in five of 15 cell lines, it was not observed in the remaining 10 cell lines. To clarify the underlying mechanism, we examined the expression levels of the Coxsackievirus and adenovirus receptor (CAR), which is the primary receptor for adenovirus, and of the integrins αvβ3 and αvβ5, which promote adenoviral internalization. The expression level of the CAR gene showed a close correlation to adenoviral gene transduction efficiency in the tested cell lines, whereas the expression levels of the integrins did not. The CAR expression was decreased by wild-type p53 transduction in U251MG cells harboring mutant p53 and increased by antisense inhibition of p53 in LN443 cells with endogenous wild-type p53.Conclusions. The results of this study indicate that CAR expression is a critical determinant of transduction efficiencies in adenovirus-based gene therapy for human malignant gliomas.
2
O'Prey, Jim, Simon Wilkinson, and Kevin M. Ryan. "Tumor Antigen LRRC15 Impedes Adenoviral Infection: Implications for Virus-Based Cancer Therapy." Journal of Virology 82, no. 12 (April 2, 2008): 5933–39. http://dx.doi.org/10.1128/jvi.02273-07.
Full textAbstract:
ABSTRACT Adenoviruses for gene or oncolytic therapy are under development. Notable among these strategies is adenoviral delivery of the tumor suppressor p53. Since all therapeutics have limitations in certain settings, we have undertaken retroviral suppressor screens to identify genes conferring resistance to adenovirus-delivered p53. These studies identified the tumor antigen LRRC15, which is frequently overexpressed in multiple tumor types, as a repressor of cell death due to adenoviral p53. LRRC15, however, does not impede p53 function per se but impedes adenoviral infection. Specifically, LRRC15 causes redistribution of the coxsackievirus-adenovirus receptor away from the cell surface. This effect is manifested in less adenoviral binding to the surfaces of LRRC15-expressing cells. This discovery, therefore, not only is important for understanding adenoviral biology but also has potentially important implications for adenovirus-based anticancer therapeutics.
3
Jogler, Christian, Dennis Hoffmann, Dirk Theegarten, Thomas Grunwald, Klaus Überla, and Oliver Wildner. "Replication Properties of Human Adenovirus In Vivo and in Cultures of Primary Cells from Different Animal Species." Journal of Virology 80, no. 7 (April 1, 2006): 3549–58. http://dx.doi.org/10.1128/jvi.80.7.3549-3558.2006.
Full textAbstract:
ABSTRACT Oncolytic adenoviruses have emerged as a promising approach for the treatment of tumors resistant to other treatment modalities. However, preclinical safety studies are hampered by the lack of a permissive nonhuman host. Screening of a panel of primary cell cultures from seven different animal species revealed that porcine cells support productive replication of human adenovirus type 5 (Ad5) nearly as efficiently as human A549 cells, while release of infectious virus by cells from other animal species tested was diminished by several orders of magnitude. Restriction of productive Ad5 replication in rodent and rabbit cells seems to act primarily at a postentry step. Replication efficiency of adenoviral vectors harboring different E1 deletions or mutations in porcine cells was similar to that in A549 cells. Side-by-side comparison of the viral load kinetics in blood of swine and mice injected with Ad5 or a replication-deficient adenoviral vector failed to provide clear evidence for virus replication in mice. In contrast, evidence suggests that adenovirus replication occurs in swine, since adenoviral late gene expression produced a 13.5-fold increase in viral load in an individual swine from day 3 to day 7 and 100-fold increase in viral DNA levels in the Ad5-infected swine compared to the animal receiving a replication-deficient adenovirus. Lung histology of Ad5-infected swine revealed a severe interstitial pneumonia. Although the results in swine are based on a small number of animals and need to be confirmed, our data strongly suggest that infection of swine with human adenovirus or oncolytic adenoviral vectors is a more appropriate animal model to study adenoviral pathogenicity or pharmacodynamic and toxicity profiles of adenoviral vectors than infection of mice.
4
Harrod, Kevin S., Bruce C. Trapnell, Kazuhisa Otake, Thomas R. Korfhagen, and Jeffrey A. Whitsett. "SP-A enhances viral clearance and inhibits inflammation after pulmonary adenoviral infection." American Journal of Physiology-Lung Cellular and Molecular Physiology 277, no. 3 (September 1, 1999): L580—L588. http://dx.doi.org/10.1152/ajplung.1999.277.3.l580.
Full textAbstract:
Surfactant protein A (SP-A) is a member of the collectin family of host defense molecules expressed primarily in the epithelial cells of the lung. To determine the role of SP-A in pulmonary adenoviral infection, SP-A-deficient (SP-A −/−) mice were intratracheally infected with a replication-deficient recombinant adenovirus, Av1Luc1. Lung inflammation was markedly increased in SP-A −/− compared with SP-A +/+ mice and was associated with increased hemorrhage and epithelial cell injury. Polymorphonuclear cells in bronchoalveolar lavage fluid (BALF) were increased in SP-A −/− mice after administration of adenovirus. Coadministration of adenovirus and purified human SP-A ameliorated adenoviral-induced lung inflammation in SP-A −/− mice. Concentrations of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β were increased in BALF of SP-A −/− mice. Likewise, TNF-α, IL-6, macrophage inflammatory protein (MIP)-1α, monocyte chemotactic protein-1, and MIP-2 mRNAs were increased in lung homogenates from SP-A −/− mice 6 and 24 h after viral administration. Clearance of adenoviral DNA from the lung and uptake of fluorescent-labeled adenovirus by alveolar macrophages were decreased in SP-A −/− mice. SP-A enhances viral clearance and inhibits lung inflammation during pulmonary adenoviral infection, providing support for the importance of SP-A in antiviral host defense.
5
Zhu, Jiangao, Xiaopei Huang, and Yiping Yang. "Innate Immune Response to Adenoviral Vectors Is Mediated by both Toll-Like Receptor-Dependent and -Independent Pathways." Journal of Virology 81, no. 7 (January 17, 2007): 3170–80. http://dx.doi.org/10.1128/jvi.02192-06.
Full textAbstract:
ABSTRACT Recombinant adenoviral vectors have been widely used for gene therapy applications and as vaccine vehicles for treating infectious diseases such as human immunodeficiency virus disease. The innate immune response to adenoviruses represents the most significant hurdle in clinical application of adenoviral vectors for gene therapy, but it is an attractive feature for vaccine development. How adenovirus activates innate immunity remains largely unknown. Here we showed that adenovirus elicited innate immune response through the induction of high levels of type I interferons (IFNs) by both plasmacytoid dendritic cells (pDCs) and non-pDCs such as conventional DCs and macrophages. The innate immune recognition of adenovirus by pDCs was mediated by Toll-like receptor 9 (TLR9) and was dependent on MyD88, whereas that by non-pDCs was TLR independent through cytosolic sensing of adenoviral DNA. Furthermore, type I IFNs were pivotal in innate and adaptive immune responses to adenovirus in vivo, and type I IFN blockade diminished immune responses, resulting in more stable transgene expression and reduction of inflammation. These findings indicate that adenovirus activates innate immunity by its DNA through TLR-dependent and -independent pathways in a cell type-specific fashion, and they highlight a critical role for type I IFNs in innate and adaptive immune responses to adenoviral vectors. Our results that suggest strategies to interfere with type I IFN pathway may improve the outcome of adenovirus-mediated gene therapy, whereas approaches to activate the type I IFN pathway may enhance vaccine potency.
6
Lee, Minhyeok, Seulgi Kim, Oh Jung Kwon, Ji Hye Kim, Inbeom Jeong, Ji Woong Son, Moon Jun Na, Yoo Sang Yoon, Hyun Woong Park, and Sun Jung Kwon. "Treatment of Adenoviral Acute Respiratory Distress Syndrome Using Cidofovir With Extracorporeal Membrane Oxygenation." Journal of Intensive Care Medicine 32, no. 3 (November 30, 2016): 231–38. http://dx.doi.org/10.1177/0885066616681272.
Full textAbstract:
Adenovirus infections are associated with respiratory (especially upper respiratory) infection and gastrointestinal disease and occur primarily in infants and children. Although rare in adults, severe lower respiratory adenovirus infections including pneumonia are reported in specific populations, such as military recruits and immunocompromised patients. Antiviral treatment is challenging due to limited clinical experience and lack of well-controlled randomized trials. Several previously reported cases of adenoviral pneumonia showed promising efficacy of cidofovir. However, few reports discussed the efficacy of cidofovir in acute respiratory distress syndrome (ARDS). We experienced 3 cases of adenoviral pneumonia associated with ARDS and treated with cidofovir and respiratory support, including extracorporeal membrane oxygenation (ECMO). All 3 patients showed a positive clinical response to cidofovir and survival at 28 days. Cidofovir with early ECMO therapy may be a therapeutic option in adenoviral ARDS. A literature review identified 15 cases of adenovirus pneumonia associated with ARDS.
7
Debey, B. M., H. D. Lehmkuhl, C. Chard-Bergstrom, and L. A. Hobbs. "Ovine Adenovirus Serotype 7-associated Mortality in Lambs in the United States." Veterinary Pathology 38, no. 6 (November 2001): 644–48. http://dx.doi.org/10.1354/vp.38-6-644.
Full textAbstract:
Adenoviral infections were diagnosed in three neonatal lambs that died spontaneously, and no other etiologic agents were identified. Clinical signs were anorexia, weakness, abdominal distention, and sudden death. Microscopic lesions consisted of multifocal necrotizing hepatitis, multifocal subacute interstitial nephritis, and loss of enterocytes from intestinal villi. Adenovirus inclusions were identified by light microscopy in the kidneys only. Adenoviral antigen, however, was identified in the liver, kidney, and intestine of the lambs by immunohistochemical techniques. An ovine adenovirus serotype 7, not previously isolated from sheep in the United States, was characterized from these lambs.
8
Bayer, Wibke, Matthias Tenbusch, Ruth Lietz, Lena Johrden, Simone Schimmer, Klaus Überla, Ulf Dittmer, and Oliver Wildner. "Vaccination with an Adenoviral Vector That Encodes and Displays a Retroviral Antigen Induces Improved Neutralizing Antibody and CD4+ T-Cell Responses and Confers Enhanced Protection." Journal of Virology 84, no. 4 (December 9, 2009): 1967–76. http://dx.doi.org/10.1128/jvi.01840-09.
Full textAbstract:
ABSTRACT We present a new type of adenoviral vector that both encodes and displays a vaccine antigen on the capsid, thus combining in itself gene-based and protein vaccination; this vector resulted in an improved vaccination outcome in the Friend virus (FV) model. For presentation of the envelope protein gp70 of Friend murine leukemia virus on the adenoviral capsid, gp70 was fused to the adenovirus capsid protein IX. When compared to vaccination with conventional FV Env- and Gag-encoding adenoviral vectors, vaccination with the adenoviral vector that encodes and displays pIX-gp70 combined with an FV Gag-encoding vector resulted in significantly improved protection against systemic FV challenge infection, with highly controlled viral loads in plasma and spleen. This improved protection correlated with improved neutralizing antibody titers and stronger CD4+ T-cell responses. Using a vector that displays gp70 without encoding it, we found that while the antigen display on the capsid alone was sufficient to induce high levels of binding antibodies, in vivo expression was necessary for the induction of neutralizing antibodies. This new type of adenovirus-based vaccine could be a valuable tool for vaccination.
9
B, Tadesse. "Review on Adeno Virus; As a Vaccine Vehicle." Open Access Journal of Veterinary Science & Research 2, no. 3 (2017): 1–12. http://dx.doi.org/10.23880/oajvsr-16000138.
Full textAbstract:
Adenoviruses have moved to the forefront of vaccinology and are showing substantial prom ise as vehicles for antigen delivery for a number of vaccines currently being developed. Most studies to date have focused on human serotype adenoviruses, particularly human adenovirus type 5. Human serotype adenovirus vaccine vectors are particularly usef ul for development of veterinary vaccines as neutralizing antibodies to the vector will not usually be present in the vaccinates. Most vectors currently used as vaccine carriers are deleted in E1 gene. The original E1 deleted adenoviral vectors were constr ucted by homologous recombination. Replication incompetent vectors contain an antigen expression cassette substituted for the deleted E1A – E1B region. These replication incompitant adenoviruses can not replicate because of the deletion of the essential vir al E1 gene region containing two genes. Replication competent adenoviral vectors encode all of the remaining adenoviral antigens in addition to the transgene product, i.e., the vaccine antigen. The potential for adenoviruses to elicit powerful B cell and T cell responses in the mammalian host are the main reason for the use of these vectors in vaccine development. For effective veterinary use, extensive research on adenoviral vaccine vectors should be undertaken.
10
Jakubczak, John L., Michele L. Rollence, David A. Stewart, Jonathon D. Jafari, Dan J. Von Seggern, Glen R. Nemerow, Susan C. Stevenson, and Paul L. Hallenbeck. "Adenovirus Type 5 Viral Particles Pseudotyped with Mutagenized Fiber Proteins Show Diminished Infectivity of Coxsackie B-Adenovirus Receptor-Bearing Cells." Journal of Virology 75, no. 6 (March 15, 2001): 2972–81. http://dx.doi.org/10.1128/jvi.75.6.2972-2981.2001.
Full textAbstract:
ABSTRACT A major limitation of adenovirus type 5 (Ad5)-based gene therapy, the inability to target therapeutic genes to selected cell types, is attributable to the natural tropism of the virus for the widely expressed coxsackievirus-adenovirus receptor (CAR) protein. Modifications of the Ad5 fiber knob domain have been shown to alter the tropism of the virus. We have developed a novel system to rapidly evaluate the function of modified fiber proteins in their most relevant context, the adenoviral capsid. This transient transfection/infection system combines transfection of cells with plasmids that express high levels of the modified fiber protein and infection with Ad5.βgal.ΔF, an E1-, E3-, and fiber-deleted adenoviral vector encoding β-galactosidase. We have used this system to test the adenoviral transduction efficiency mediated by a panel of fiber protein mutants that were proposed to influence CAR interaction. A series of amino acid modifications were incorporated via mutagenesis into the fiber expression plasmid, and the resulting fiber proteins were subsequently incorporated onto adenoviral particles. Mutations located in the fiber knob AB and CD loops demonstrated the greatest reduction in fiber-mediated gene transfer in HeLa cells. We also observed effects on transduction efficiency with mutations in the FG loop, indicating that the binding site may extend to the adjacent monomer in the fiber trimer and in the HI loop. These studies support the concept that modification of the fiber knob domain to diminish or ablate CAR interaction should result in a detargeted adenoviral vector that can be combined simultaneously with novel ligands for the development of a systemically administered, targeted adenoviral vector.
11
Bründler, Marie-Anne, Norberto Rodriguez-Baez, Ron Jaffe, Arthur G. Weinberg, and Beverly Barton Rogers. "Adenovirus Ascending Cholangiohepatitis." Pediatric and Developmental Pathology 6, no. 2 (March 2003): 156–59. http://dx.doi.org/10.1007/s10024-002-0063-4.
Full textAbstract:
Three children, two with liver transplants and one with acquired human immunodeficiency virus (HIV) infection, presented with hepatitis accompanied by elevated gamma glutamyl transpeptidase. Biopsies revealed cholangiohepatitis caused by adenovirus infection. There was a progressive loss of interlobular bile ducts in two of the patients. In one patient, infection of the biliary tree was marked by a necrotizing cholangitis, with adenoviral inclusions noted in the biliary epithelium. In each patient, there was evidence of adenovirus gastrointestinal infection. This is the first report of adenoviral infection of the biliary tree in humans. It is hypothesized that adenovirus cholangiohepatitis occurs as a result of ascending infection from the gastrointestinal tract to the biliary tree.
12
Yarovinsky, Timur O., Michael P. Mohning, Mary A. Bradford, Martha M. Monick, and Gary W. Hunninghake. "Increased Sensitivity to Staphylococcal Enterotoxin B following Adenoviral Infection." Infection and Immunity 73, no. 6 (June 2005): 3375–84. http://dx.doi.org/10.1128/iai.73.6.3375-3384.2005.
Full textAbstract:
ABSTRACT Staphylococcal enterotoxin B induces toxic shock and is a major virulence factor of staphylococcal diseases. We examined the effects of systemic adenoviral infection on responses to staphylococcal enterotoxin B in a murine model. We found that adenoviral infection markedly increases the severity of liver injury following exposure to staphylococcal enterotoxin B without d-galactosamine sensitization. In adenovirus-infected mice, staphylococcal enterotoxin B triggered a more profound hypothermia and increased apoptosis in the liver. Consistent with these observations, we also found that adenoviral infection primed for an increased production of gamma interferon in vivo and in vitro following stimulation with staphylococcal enterotoxin B. Gamma-interferon-knockout mice did not show increased sensitivity to staphylococcal enterotoxin B following adenoviral infection. These data suggest that a preexisting viral infection primes mice for subsequent staphylococcal enterotoxin B exposure, possibly via a gamma-interferon-mediated mechanism.
13
Wold, William S. M., Ann E. Tollefson, Baoling Ying, Jacqueline F. Spencer, and Karoly Toth. "Drug development against human adenoviruses and its advancement by Syrian hamster models." FEMS Microbiology Reviews 43, no. 4 (March 27, 2019): 380–88. http://dx.doi.org/10.1093/femsre/fuz008.
Full textAbstract:
ABSTRACTThe symptoms of human adenovirus infections are generally mild and self-limiting. However, these infections have been gaining importance in recent years because of a growing number of immunocompromised patients. Solid organ and hematopoietic stem cell transplant patients are subjected to severe immunosuppressive regimes and cannot efficaciously eliminate virus infections. In these patients, adenovirus infections can develop into deadly multi-organ disseminated disease. Presently, in the absence of approved therapies, physicians rely on drugs developed for other purposes to treat adenovirus infections. As there is a need for anti-adenoviral therapies, researchers have been developing new agents and repurposing existing ones to treat adenovirus infections. There are several small molecule drugs that are being tested for their efficacy against human adenoviruses; some of these have reached clinical trials, while others are still in the preclinical phase. Besides these compounds, research on immunotherapy against adenoviral infection has made significant progress, promising another modality for treatment. The availability of an animal model confirmed the activity of some drugs already in clinical use while proving that others are inactive. This led to the identification of several lead compounds that await further development. In the present article, we review the current status of anti-adenoviral therapies and their advancement by in vivo studies in the Syrian hamster model.
14
Weger, Stefan, Eva Hammer, Melanie Gonsior, Catrin Stutika, and Regine Heilbronn. "A Regulatory Element Near the 3′ End of the Adeno-Associated VirusrepGene Inhibits Adenovirus Replication incisby Means of p40 Promoter-Associated Short Transcripts." Journal of Virology 90, no. 8 (February 3, 2016): 3981–93. http://dx.doi.org/10.1128/jvi.03120-15.
Full textAbstract:
ABSTRACTAdeno-associated virus (AAV) has long been known to inhibit helper adenovirus (Ad) replication independently of AAV Rep protein expression. More recently, replication of Ad serotype 5 (Ad5)/AAV serotype 2 (AAV-2) hybrid vectors was shown to be inhibited incisby a sequence near the 3′ end of AAVrep, termed the Rep inhibition sequence for adenoviral replication (RIS-Ad). RIS-Ad functions independently of Rep protein expression. Here we demonstrate that inhibition of adenoviral replication by RIS-Ad requires an active AAV p40 promoter and the 5′ half of the intron. In addition, Ad inhibition is critically dependent on the integrity of the p40 transcription start site (TSS) leading to short p40-associated transcripts. These do not give rise to effector molecules capable of inhibiting adenoviral replication intrans, like small polypeptides or microRNAs. Our data point to an inhibitory mechanism in which RNA polymerase II (Pol II) pauses directly downstream of the p40 promoter, leading to interference of the stalled Pol II transcription complex with the adenoviral replication machinery. Whereas inhibition by RIS-Ad is mediated exclusively incis, it can be overcome by providing a replication-competent adenoviral genome intrans. Moreover, the inhibitory effect of RIS-Ad is not limited to AAV-2 but could also be shown for the corresponding regions of other AAV serotypes, including AAV-5. These findings have important implications for the future generation of Ad5/AAV hybrid vectors.IMPORTANCEInsertion of sequences from the 3′ part of therepgene of adeno-associated virus (AAV) into the genome of its helper adenovirus strongly reduces adenoviral genome replication. We could show that this inhibition is mediated exclusively inciswithout the involvement oftrans-acting regulatory RNAs or polypeptides but nevertheless requires an active AAV-2 p40 promoter and p40-associated short transcripts. Our results suggest a novel inhibitory mechanism that has so far not been described for AAV and that involves stalled RNA polymerase II complexes and their interference with adenoviral DNA replication. Such a mechanism would have important implications both for the generation of adenoviral vectors expressing the AAVrepandcapgenes and for the regulation of AAV gene expression in the absence and presence of helper virus.
15
Leen, Ann M., Anne Christin, Gary D. Myers, Hao Liu, Conrad R. Cruz, Patrick J. Hanley, Alana A. Kennedy-Nasser, et al. "Cytotoxic T lymphocyte therapy with donor T cells prevents and treats adenovirus and Epstein-Barr virus infections after haploidentical and matched unrelated stem cell transplantation." Blood 114, no. 19 (November 5, 2009): 4283–92. http://dx.doi.org/10.1182/blood-2009-07-232454.
Full textAbstract:
Abstract Viral infection or reactivation remains a major cause of morbidity and mortality after allogeneic stem cell transplantation. We now show that infusions of single cytotoxic T lymphocyte (CTL) lines (5 × 106-1.35 × 108 cells/m2) with specificity for 2 commonly detected viruses, Epstein-Barr virus (EBV) and adenovirus, can be safely administered to pediatric transplantation recipients receiving partially human leukocyte antigen–matched and haploidentical stem cell grafts (n = 13), without inducing graft-versus-host disease. The EBV-specific component of the CTLs expanded in vivo and persisted for more than 12 weeks, but the adenovirus-specific component only expanded in vivo in the presence of concomitant adenoviral infection. Nevertheless, adenovirus-specific T cells could be detected for at least 8 weeks in peripheral blood, even in CTL recipients without viral infection, provided the adenovirus-specific component of their circulating lymphocytes was first expanded by exposure to adenoviral antigens ex vivo. After infusion, none of these 13 high-risk recipients developed EBV-associated lymphoproliferative disease, while 2 of the subjects had resolution of their adenoviral disease. Hence, bispecific CTLs containing both EBV- and adenovirus-specific T cells can safely reconstitute an antigen responsive “memory” population of CTLs after human leukocyte antigen–mismatched stem cell transplantation and may provide antiviral activity. This trial was registered at www.clinicaltrials.gov as #NCT00590083.
16
Sundaramurthy, Raja, Rahul Dhodapkar, Subashini Kaliaperumal, and Belgode Narasimha Harish. "Investigational approach to adenoviral conjunctivitis: comparison of three diagnostic tests using a Bayesian latent class model." Journal of Infection in Developing Countries 12, no. 01 (January 31, 2018): 043–51. http://dx.doi.org/10.3855/jidc.9439.
Full textAbstract:
Introduction: Highly contagious adenoviral conjunctivitis represents 15-70% of all conjunctivitis worldwide. Human adenovirus (hAdV) serotypes 3,4,7,8,19 and 37 contributes to 89% of all adenoviral conjunctivitis. Accurate and rapid diagnosis of adenoviral infections at serotype level could prevent misdiagnosis, spread of disease, unnecessary antibiotic use and increased treatment costs.
Methodology: Sixty-two suspected viral conjunctivitis cases were recruited from November2013-January2015. Swabs collected from inferior palpebral conjunctiva and processed for viral culture (Hep2 cell line), immunofluorescence assay (IFA) and polymerase chain reaction (PCR) (targeting hexon gene). Serotype 3,4,7,8,19 and 37 identification was carried out with an optimized multiplex-PCR (based on hypervariable region of hexon gene) and confirmed by sequence analysis. Bayesian Latent Class Model (LCM) analysis was used to compare sensitivity and specificity of three tests.
Results: Adenovirus was detected in 54.8% (34/62) of cases by combination of all three methods. Culture was positive in 23/34 cases (67.6%). PCR and IFA detected adenovirus in 24 (70.5%) and 21 (61.7%) cases respectively. LCM analysis revealed, sensitivity and specificity of PCR, Culture and IFA was 77.8% and 92.4%; 72.2% and 90.8%; 67.6% and 92.9% respectively. Serotyping by multiplex-PCR showed, two cases each were hAdV3 and hAdV4, 18 hAdV8 and two remained unidentified. Results of Multiplex-PCR and sequence analysis showed 100% concordance
Conclusion: LCM analysis revealed, PCR is the most appropriate method for identification. Multiplex-PCR is a simple and rapid method (serotypes identification within two days); owing its short turnaround time and accuracy, it can be used as a diagnostic tool for surveillance of adenoviral keratoconjunctivitis.
17
Kuo, Irene C., and Colleen Espinosa. "Five-year trends in adenoviral conjunctivitis in employees of one medical center." Infection Control & Hospital Epidemiology 39, no. 9 (June 28, 2018): 1080–85. http://dx.doi.org/10.1017/ice.2018.145.
Full textAbstract:
ObjectiveTo describe the 5-year findings after a policy to screen for, diagnose, and isolate medical center employees with adenoviral conjunctivitis was implemented.DesignObservational report with a retrospective evaluation of a current quality improvement initiative.SettingJohns Hopkins Medicine, Baltimore, Maryland.ParticipantsJohns Hopkins Medicine employees.MethodsData were retrieved from records maintained for this initiative, in which employees with suspected adenoviral conjunctivitis were evaluated in the Occupational Health Clinic and swabbed for polymerase chain reaction (PCR) testing for adenoviral conjunctivitis. Signs, symptoms, work area, diagnoses, and disposition of employees with eye complaints as well as PCR result and adenoviral type were recorded. Five-year data were reviewed.ResultsFrom 2011 to 2016, of 10,000 full-time equivalent employees, 1,059 employees visited the Occupational Health Clinic with suspicion of adenoviral conjunctivitis. Of these, 104 (10%) were PCR positive for adenovirus. Of these PCR-positive employees, 26 (25%) had the worst clinical presentation, epidemic keratoconjunctivitis (EKC). The Outpatient Pharmacy had the highest number of adenoviral conjunctivitis cases (n=9). The proportion of red-eye employees having PCR-positive adenoviral conjunctivitis increased over 5 years (P<.005, Cochrane-Armitage test for trend) as did the proportion of employees with EKC (P<.05). The proportion of employees with EKC caused by type 37 also increased (P<.05).ConclusionsAdenoviral conjunctivitis represents 10% of employee cases clinically suspected of this infection. Employees in patient-care areas should be screened even if they have no direct patient contact. Despite increases in the proportions of adenoviral conjunctivitis and of EKC over 5 years, no outbreaks occurred. This policy helps identify incipient EKC outbreaks and guides infection control efforts.
18
van Beusechem, Victor W., Jacques Grill, D. C. Jeroen Mastenbroek, Thomas J. Wickham, Peter W. Roelvink, Hidde J. Haisma, Martine L. M. Lamfers, Clemens M. F. Dirven, Herbert M. Pinedo, and Winald R. Gerritsen. "Efficient and Selective Gene Transfer into Primary Human Brain Tumors by Using Single-Chain Antibody-Targeted Adenoviral Vectors with Native Tropism Abolished." Journal of Virology 76, no. 6 (March 15, 2002): 2753–62. http://dx.doi.org/10.1128/jvi.76.6.2753-2762.2002.
Full textAbstract:
ABSTRACT The application of adenoviral vectors in cancer gene therapy is hampered by low receptor expression on tumor cells and high receptor expression on normal epithelial cells. Targeting adenoviral vectors toward tumor cells may improve cancer gene therapy procedures by providing augmented tumor transduction and decreased toxicity to normal tissues. Targeting requires both the complete abolition of native tropism and the addition of a new specific binding ligand onto the viral capsid. Here we accomplished this by using doubly ablated adenoviral vectors, lacking coxsackievirus-adenovirus receptor and αv integrin binding capacities, together with bispecific single-chain antibodies targeted toward human epidermal growth factor receptor (EGFR) or the epithelial cell adhesion molecule. These vectors efficiently and selectively targeted both alternative receptors on the surface of human cancer cells. Targeted doubly ablated adenoviral vectors were also very efficient and specific with primary human tumor specimens. With primary glioma cell cultures, EGFR targeting augmented the median gene transfer efficiency of doubly ablated adenoviral vectors 123-fold. Moreover, EGFR-targeted doubly ablated vectors were selective for human brain tumors versus the surrounding normal brain tissue. They transduced organotypic glioma and meningioma spheroids with efficiencies similar to those of native adenoviral vectors, while exhibiting greater-than-10-fold-reduced background levels on normal brain explants from the same patients. As a result, EGFR-targeted doubly ablated adenoviral vectors had a 5- to 38-fold-improved tumor-to-normal brain targeting index compared to native vectors. Hence, single-chain targeted doubly ablated adenoviral vectors are promising tools for cancer gene therapy. They should provide an improved therapeutic index with efficient tumor transduction and effective protection of normal tissue.
19
Tessarollo, Nayara Gusmão, Ana Carolina M. Domingues, Fernanda Antunes, Jean Carlos dos Santos da Luz, Otavio Augusto Rodrigues, Otto Luiz Dutra Cerqueira, and Bryan E. Strauss. "Nonreplicating Adenoviral Vectors: Improving Tropism and Delivery of Cancer Gene Therapy." Cancers 13, no. 8 (April 14, 2021): 1863. http://dx.doi.org/10.3390/cancers13081863.
Full textAbstract:
Recent preclinical and clinical studies have used viral vectors in gene therapy research, especially nonreplicating adenovirus encoding strategic therapeutic genes for cancer treatment. Adenoviruses were the first DNA viruses to go into therapeutic development, mainly due to well-known biological features: stability in vivo, ease of manufacture, and efficient gene delivery to dividing and nondividing cells. However, there are some limitations for gene therapy using adenoviral vectors, such as nonspecific transduction of normal cells and liver sequestration and neutralization by antibodies, especially when administered systemically. On the other hand, adenoviral vectors are amenable to strategies for the modification of their biological structures, including genetic manipulation of viral proteins, pseudotyping, and conjugation with polymers or biological membranes. Such modifications provide greater specificity to the target cell and better safety in systemic administration; thus, a reduction of antiviral host responses would favor the use of adenoviral vectors in cancer immunotherapy. In this review, we describe the structural and molecular features of nonreplicating adenoviral vectors, the current limitations to their use, and strategies to modify adenoviral tropism, highlighting the approaches that may allow for the systemic administration of gene therapy.
20
Dumitrescu, Madalina, Ana Maria Vacaru, Violeta Georgeta Trusca, Ioana Madalina Fenyo, Radu Ionita, and Anca Violeta Gafencu. "K2 Transfection System Boosts the Adenoviral Transduction of Murine Mesenchymal Stromal Cells." International Journal of Molecular Sciences 22, no. 2 (January 9, 2021): 598. http://dx.doi.org/10.3390/ijms22020598.
Full textAbstract:
Adenoviral vectors are important vehicles for delivering therapeutic genes into mammalian cells. However, the yield of the adenoviral transduction of murine mesenchymal stromal cells (MSC) is low. Here, we aimed to improve the adenoviral transduction efficiency of bone marrow-derived MSC. Our data showed that among all the potential transduction boosters that we tested, the K2 Transfection System (K2TS) greatly increased the transduction efficiency. After optimization of both K2TS components, the yield of the adenoviral transduction increased from 18% to 96% for non-obese diabetic (NOD)-derived MSC, from 30% to 86% for C57BL/6-derived MSC, and from 0.6% to 63% for BALB/c-derived MSC, when 250 transduction units/cell were used. We found that MSC derived from these mouse strains expressed different levels of the coxsackievirus and adenovirus receptors (MSC from C57BL/6≥NOD>>>BALB/c). K2TS did not increase the level of the receptor expression, but desensitized the cells to foreign DNA and facilitated the virus entry into the cell. The expression of Stem cells antigen-1 (Sca-1) and 5′-nucleotidase (CD73) MSC markers, the adipogenic and osteogenic differentiation potential, and the immunosuppressive capacity were preserved after the adenoviral transduction of MSC in the presence of the K2TS. In conclusion, K2TS significantly enhanced the adenoviral transduction of MSC, without interfering with their main characteristics and properties.
21
Dumitrescu, Madalina, Ana Maria Vacaru, Violeta Georgeta Trusca, Ioana Madalina Fenyo, Radu Ionita, and Anca Violeta Gafencu. "K2 Transfection System Boosts the Adenoviral Transduction of Murine Mesenchymal Stromal Cells." International Journal of Molecular Sciences 22, no. 2 (January 9, 2021): 598. http://dx.doi.org/10.3390/ijms22020598.
Full textAbstract:
Adenoviral vectors are important vehicles for delivering therapeutic genes into mammalian cells. However, the yield of the adenoviral transduction of murine mesenchymal stromal cells (MSC) is low. Here, we aimed to improve the adenoviral transduction efficiency of bone marrow-derived MSC. Our data showed that among all the potential transduction boosters that we tested, the K2 Transfection System (K2TS) greatly increased the transduction efficiency. After optimization of both K2TS components, the yield of the adenoviral transduction increased from 18% to 96% for non-obese diabetic (NOD)-derived MSC, from 30% to 86% for C57BL/6-derived MSC, and from 0.6% to 63% for BALB/c-derived MSC, when 250 transduction units/cell were used. We found that MSC derived from these mouse strains expressed different levels of the coxsackievirus and adenovirus receptors (MSC from C57BL/6≥NOD>>>BALB/c). K2TS did not increase the level of the receptor expression, but desensitized the cells to foreign DNA and facilitated the virus entry into the cell. The expression of Stem cells antigen-1 (Sca-1) and 5′-nucleotidase (CD73) MSC markers, the adipogenic and osteogenic differentiation potential, and the immunosuppressive capacity were preserved after the adenoviral transduction of MSC in the presence of the K2TS. In conclusion, K2TS significantly enhanced the adenoviral transduction of MSC, without interfering with their main characteristics and properties.
22
Afrough, Sara, Sophie Rhodes, Thomas Evans, Richard White, and John Benest. "Immunologic Dose-Response to Adenovirus-Vectored Vaccines in Animals and Humans: A Systematic Review of Dose-Response Studies of Replication Incompetent Adenoviral Vaccine Vectors when Given via an Intramuscular or Subcutaneous Route." Vaccines 8, no. 1 (March 17, 2020): 131. http://dx.doi.org/10.3390/vaccines8010131.
Full textAbstract:
Optimal vaccine dosing is important to ensure the greatest protection and safety. Analysis of dose-response data, from previous studies, may inform future studies to determine the optimal dose. Implementing more quantitative modelling approaches in vaccine dose finding have been recently suggested to accelerate vaccine development. Adenoviral vectored vaccines are in advanced stage of development for a variety of prophylactic and therapeutic indications, however dose-response has not yet been systematically determined. To further inform adenoviral vectored vaccines dose identification, historical dose-response data should be systematically reviewed. A systematic literature review was conducted to collate and describe the available dose-response studies for adenovirus vectored vaccines. Of 2787 papers identified by Medline search strategy, 35 were found to conform to pre-defined criteria. The majority of studies were in mice or humans and studied adenovirus serotype 5. Dose-response data were available for 12 different immunological responses. The majority of papers evaluated three dose levels, only two evaluated more than five dose levels. The most common dosing range was 107–1010 viral particles in mouse studies and 108–1011 viral particles in human studies. Data were available on adenovirus vaccine dose-response, primarily on adenovirus serotype 5 backbones and in mice and humans. These data could be used for quantitative adenoviral vectored vaccine dose optimisation analysis.
23
Chirmule, Narendra, Steven E. Raper, Linda Burkly, David Thomas, John Tazelaar, Joseph V. Hughes, and James M. Wilson. "Readministration of Adenovirus Vector in Nonhuman Primate Lungs by Blockade of CD40-CD40 Ligand Interactions." Journal of Virology 74, no. 7 (April 1, 2000): 3345–52. http://dx.doi.org/10.1128/jvi.74.7.3345-3352.2000.
Full textAbstract:
ABSTRACT The interaction between CD40 on B cells and CD40 ligand (CD40L) on activated T cells is important for B-cell differentiation in T-cell-dependent humoral responses. We have extended our previous murine studies of CD40-CD40L in adenoviral vector-mediated immune responses to rhesus monkeys. Primary immune responses to adenoviral vectors and the ability to readminister vector were studied in rhesus monkeys in the presence or absence of a transient treatment with a humanized anti-CD40 ligand antibody (hu5C8). Adult animals were treated with hu5C8 at the time vector was instilled into the lung. Immunological analyses demonstrated suppression of adenovirus-induced lymphoproliferation and cytokine responses (interleukin-2 [IL-2], gamma interferon, IL-4, and IL-10) in hu5C8-treated animals. Animals treated with hu5C8 secreted adenovirus-specific immunoglobulin M (IgM) levels comparable to control animals, but did not secrete IgA or develop neutralizing antibodies; consequently, the animals could be readministered with adenovirus vector expressing alkaline phosphatase. A second study was designed to examine the long-term effects on immune functions of a short course of hu5C8. Acute hu5C8 treatment resulted in significant and prolonged inhibition of the adenovirus-specific humoral response well beyond the time hu5C8 effects were no longer significant. These studies demonstrate the potential of hu5C8 as an immunomodulatory regimen to enable administration of adenoviral vectors, and they advocate testing this model in humans.
24
Yu, Qing, Loretta G. Que, and Don C. Rockey. "Adenovirus-mediated gene transfer to nonparenchymal cells in normal and injured liver." American Journal of Physiology-Gastrointestinal and Liver Physiology 282, no. 3 (March 1, 2002): G565—G572. http://dx.doi.org/10.1152/ajpgi.00512.2000.
Full textAbstract:
Adenovirus-mediated gene transfer has become an important tool with which to introduce genetic material into cells. Available data emphasize efficient adenoviral transduction of parenchymal liver cells (i.e., hepatocytes) in both in vitro and in vivo model systems, typically in normal cells. The aim of this study was to evaluate gene transfer to nonparenchymal (and parenchymal) cells of the normal and injured rat liver. Hepatocytes, stellate cells, and endothelial cells were isolated by standard methods. Liver injury was induced by bile duct ligation or carbon tetrachloride administration. Cells were transduced in vitro with an adenovirus encoding β-galactosidase (Ad.β-gal) over a range of viral titers, and transduced cells were identified by detection of X-gal. In vivo transduction efficiency was studied in normal and injured livers using cell isolation techniques. Nonparenchymal cells were transduced with greater frequency than hepatocytes at all adenoviral titers tested, both in vitro and in vivo. After liver injury, adenoviral transduction was reduced for all liver cell types compared with that for cells from normal livers (at all virus titers). Notably, transduction efficiency remained greater in nonparenchymal cells than in hepatocytes after liver injury. This work implies that, to achieve comparable gene expression in the injured liver, higher adenoviral titers may be required, an important consideration as gene therapy in disease states is considered.
25
Barcia, Carlos, Christian Gerdes, Wei-Dong Xiong, Clare E. Thomas, Chunyan Liu, Kurt M. Kroeger, Maria G. Castro, and Pedro R. Lowenstein. "Immunological thresholds in neurological gene therapy: highly efficient elimination of transduced cells might be related to the specific formation of immunological synapses between T cells and virus-infected brain cells." Neuron Glia Biology 2, no. 4 (November 2006): 309–22. http://dx.doi.org/10.1017/s1740925x07000579.
Full textAbstract:
AbstractFirst-generation adenovirus can be engineered with powerful promoters to drive expression of therapeutic transgenes. Numerous clinical trials for glioblastoma multiforme using first generation adenoviral vectors have either been performed or are ongoing, including an ongoing, Phase III, multicenter trial in Europe and Israel (Ark Therapeutics, Inc.). Although in the absence of anti-adenovirus immune responses expression in the brain lasts 6–18 months, systemic infection with adenovirus induces immune responses that inhibit dramatically therapeutic transgene expression from first generation adenoviral vectors, thus, potentially compromising therapeutic efficacy. Here, we show evidence of an immunization threshold for the dose that generates an immune response strong enough to eliminate transgene expression from the CNS. For the systemic immunization to eliminate transgene expression from the brain, ≥1×107 infectious units (iu) of adenovirus need to be used as immunogen. Furthermore, this immune response eliminates >90% of transgene expression from 1×107–1×103 iu of vector injected into the striatum 60 days earlier. Importantly, elimination of transgene expression is independent of the nature of the promoter that drives transgene expression and is accompanied by brain infiltration of CD8+ T cells and macrophages. In conclusion, once the threshold for systemic immunization (i.e. 1×107 iu) is crossed, the immune response eliminates transgene expression by >90% even from brains that receive as little as 1000 iu of adenoviral vectors, independently of the type of promoter that drives expression.
26
Ikegami, Machiko, Kevin S. Harrod, Jeffrey A. Whitsett, and Alan H. Jobe. "CCSP deficiency does not alter surfactant homeostasis during adenoviral infection." American Journal of Physiology-Lung Cellular and Molecular Physiology 277, no. 5 (November 1, 1999): L983—L987. http://dx.doi.org/10.1152/ajplung.1999.277.5.l983.
Full textAbstract:
Clara cell secretory protein (CCSP) deficiency in mice is associated with increased susceptibility to pulmonary inflammation after hyperoxia or viral infection. Because adenoviral exposure perturbs pulmonary surfactant homeostasis in vivo, we hypothesized that CCSP deficiency would influence surfactant metabolism after pulmonary infection. Alveolar and total lung saturated phosphatidylcholine pool sizes were similar in CCSP-deficient [CCSP(−/−)] and wild-type [CCSP(+/+)] mice before and 7 days after intratracheal administration of adenovirus. Radiolabeled choline and palmitate incorporation into saturated phosphatidylcholine was similar, and there was no alteration by previous infection 7 days before the incorporation measurements. Furthermore, CCSP deficiency did not influence clearance of [14C]dipalmitoylphosphatidylcholine and 125I-labeled recombinant surfactant protein C. Increased persistence of alveolar capillary leak was observed in CCSP(−/−) mice after adenoviral infection. Surfactant lipid homeostasis was not influenced by CCSP before or after administration of adenovirus to the lung. Persistence of alveolar capillary leak in CCSP(−/−) mice after adenovirus provides further evidence for the role of CCSP in the regulation of pulmonary inflammation.
27
Karimi, Ali, Mohammad-Taghi Moradi, Mohammad Rabiei, and Somayeh Alidadi. "In vitro anti-adenoviral activities of ethanol extract, fractions, and main phenolic compounds of pomegranate (Punica granatum L.) peel." Antiviral Chemistry and Chemotherapy 28 (January 2020): 204020662091657. http://dx.doi.org/10.1177/2040206620916571.
Full textAbstract:
Background Adenovirus causes a number of diseases in human, and can cause serious infection in severely immunosuppressed individuals. Despite the seriousness of adenovirus infection, there is no definitely approved anti-adenoviral therapy. Many studies have shown that compounds derived from medicinal plants have antiviral activity. Therefore, this study evaluated in vitro anti-adenoviral activity of ethanol extract, fractions, and main phenolic compounds of pomegranate peel. Methods The ethanol extract of pomegranate peel was prepared with maceration method and fractionated by consecutive liquid/liquid partition. The cytotoxic and anti-adenovirus activities of the extract, fractions, and main phenolic compounds (ellagic acid, punicalagin and gallic acid) were evaluated on Hep-2 cell line using MTT assay. Inhibitory effect on adsorption and post-adsorption phases of the virus replication cycle was also evaluated. Results Pomegranate peel extract had a desirable effect against adenovirus with IC50 of 5.77 µg/mL and selectivity index of 49.9. Among the fractions and compounds, the n-butanol fraction and gallic acid had the highest anti-adenoviral activity with IC50 of 2.16 µg/mL and 4.67 µM and selectivity indices of 122.5 and 10.5, respectively. The crude extract, n-butanol fraction and gallic acid inhibited the virus replication in post-adsorption phase ( p < 0.01). Conclusion Pomegranate peel extract, especially its n-butanol fraction, could serve as a new promising anti-adenovirus agent due to high inhibitory effect against adenovirus replication. The effect of the n-butanol fraction may be related to the synergistic effect or other compounds of this fraction. Further understanding of the bioassay guided isolation of natural compounds of this fraction seems essential.
28
Xiang, Zhiquan, Guangping Gao, Arturo Reyes-Sandoval, Christopher J. Cohen, Yan Li, Jeffrey M. Bergelson, James M. Wilson, and Hildegund C. J. Ertl. "Novel, Chimpanzee Serotype 68-Based Adenoviral Vaccine Carrier for Induction of Antibodies to a Transgene Product." Journal of Virology 76, no. 6 (March 15, 2002): 2667–75. http://dx.doi.org/10.1128/jvi.76.6.2667-2675.2002.
Full textAbstract:
ABSTRACT An E1-deletion-containing adenoviral recombinant based on the chimpanzee serotype 68 (AdC68) was developed to express the rabies virus glycoprotein. Mice immunized with this construct (AdC68rab.gp) developed antibodies to rabies virus and remained resistant to challenge with an otherwise lethal dose of rabies virus. In naïve mice immunized intranasally, the rabies virus-specific antibody responses elicited by AdC68rab.gp were comparable with regard to both titers and isotype profiles to those induced by an adenoviral recombinant based on human serotype 5 (Adhu5) expressing the same transgene product. In contrast, subcutaneous immunization with the AdC68rab.gp vaccine resulted in markedly lower antibody responses to the rabies virus glycoprotein than the corresponding Adhu5 vaccine. Antibodies from AdC68rab.gp-immunized mice were strongly biased towards the immunoglobulin G2a isotype. The antibody response to the rabies virus glycoprotein presented by Adhu5rab.gp was severely compromised in animals preexposed to the homologous adenovirus. In contrast, the rabies virus-specific antibody response to the AdC68rab.gp vaccine was at most marginally affected by preexisting immunity to common human adenovirus serotypes, such as 2, 4, 5, 7, and 12. This novel vaccine carrier thus offers a distinct advantage over adenoviral vaccines based on common human serotypes.
29
Deng, Weiwen, Troy A. Giambernardi, Rick V. Hay, Daniel W. Pietryga, and Aly S. Abdel-Mageed. "Adenovirus-Mediated Gene Transfer to Mesenchymal Stem Cells: Comparison of the Cytomegalovirus- and Rous Sarcoma Virus-Promoter." Blood 110, no. 11 (November 16, 2007): 5145. http://dx.doi.org/10.1182/blood.v110.11.5145.5145.
Full textAbstract:
Abstract We have compared the efficacy and toxicity of the cytomegalovirus (CMV) promoter and the Rous sarcoma virus (RSV) promoter for expressing genes for adenovirus-mediated gene transfer to mesenchymal stem cells (MSCs). Mouse MSCs (mMSCs) were isolated from the femurs and tibias of 6-week old, female BALB/c mice and ex vivo expanded in MEM-alpha containing 20% fetal bovine serum, 100 u/ml penicillin, 100 μg/ml streptomycin, 250 ng/ml amphotericin B, and 2 mM L-glutamine. To transduce mMSCs with adenovirus, the cells were plated at a density of 10,000 cells/cm2 in 6-well plates and cultured overnight. The cells were counted and then exposed to fresh culture medium containing adenovirus at 0 to 2,000 multiplicities of infection (MOI) for 48 h. Two adenoviral vectors with CMV promoter (Adv/CMV) and two adenoviral vectors with RSV promoter (Adv/RSV) were used in this study. Transduction efficiency and cell survival were then determined. The Adv/CMVs, i.e. AdvCMVlacZ and AdvCMVIL-10, were more potent in terms of transduction efficiency and transgene expression than their corresponding Adv/RSVs, i.e. AdvRSVlacZ and AdvRSVIL-10. However, both vectors exhibit a dose-dependent relationship between the adenoviral vector MOI and the percentage of transgene-expressing cells. Furthermore, no toxicity was observed in Adv/CMV or Adv/RSV transduced mMSCs.
30
Turner, Roberta L., Peter Groitl, Thomas Dobner, and David A. Ornelles. "Adenovirus Replaces Mitotic Checkpoint Controls." Journal of Virology 89, no. 9 (February 18, 2015): 5083–96. http://dx.doi.org/10.1128/jvi.00213-15.
Full textAbstract:
ABSTRACTInfection with adenovirus triggers the cellular DNA damage response, elements of which include cell death and cell cycle arrest. Early adenoviral proteins, including the E1B-55K and E4orf3 proteins, inhibit signaling in response to DNA damage. A fraction of cells infected with an adenovirus mutant unable to express the E1B-55K and E4orf3 genes appeared to arrest in a mitotic-like state. Cells infected early in G1of the cell cycle were predisposed to arrest in this state at late times of infection. This arrested state, which displays hallmarks of mitotic catastrophe, was prevented by expression of either the E1B-55K or the E4orf3 genes. However, E1B-55K mutant virus-infected cells became trapped in a mitotic-like state in the presence of the microtubule poison colcemid, suggesting that the two viral proteins restrict entry into mitosis or facilitate exit from mitosis in order to prevent infected cells from arresting in mitosis. The E1B-55K protein appeared to prevent inappropriate entry into mitosis through its interaction with the cellular tumor suppressor protein p53. The E4orf3 protein facilitated exit from mitosis by possibly mislocalizing and functionally inactivating cyclin B1. When expressed in noninfected cells, E4orf3 overcame the mitotic arrest caused by the degradation-resistant R42A cyclin B1 variant.IMPORTANCECells that are infected with adenovirus type 5 early in G1of the cell cycle are predisposed to arrest in a mitotic-like state in a p53-dependent manner. The adenoviral E1B-55K protein prevents entry into mitosis. This newly described activity for the E1B-55K protein appears to depend on the interaction between the E1B-55K protein and the tumor suppressor p53. The adenoviral E4orf3 protein facilitates exit from mitosis, possibly by altering the intracellular distribution of cyclin B1. By preventing entry into mitosis and by promoting exit from mitosis, these adenoviral proteins act to prevent the infected cell from arresting in a mitotic-like state.
31
Affeldt, John, Neha Gadaria-Rathod, Karen B. Fernandez, and Penny A. Asbell. "Ganciclovir in the Treatment of Ophthalmic Viral Infections – Case Reports." US Ophthalmic Review 05, no. 02 (2012): 100. http://dx.doi.org/10.17925/usor.2012.05.02.100.
Full textAbstract:
Adenovirus is likely the most common cause of eye infections but remains a challenge for ophthalmologists to diagnose as well as treat. While ganciclovir gel is approved for the topical treatment of eye infections arising due to herpes simplex virus, it is not licensed for use against adenoviral conjunctivitis. This antiviral agent selectively targets infected cells and disrupts viral DNA replication. A small study and previous anecdotal reports had illustrated the potential of ganciclovir in improving symptoms and transmissibility of adenoviral eye infections. The present article describes a series of case studies where ganciclovir was used off label in the management of the morbidity caused by adenovirus. The observations are promising and suggest that ganciclovir can be used successfully in this patient population. However, large-scale randomised trials are needed to confirm these findings.
32
Haveman, Lianne M., Berent Prakken, Mark R. Klein, Salvo Albani, and Marc Bierings. "Induction and Capture of CD4+ Cytotoxic Adenoviral Specific T-Cells in Response to pan-DR Binding Adenoviral Epitopes; towards Immunotherapy." Blood 106, no. 11 (November 16, 2005): 3238. http://dx.doi.org/10.1182/blood.v106.11.3238.3238.
Full textAbstract:
Abstract In the immunocompromised host adenovirus may cause fatal infections, especially after stem cell transplantation. No effective antiviral medication exists for severe adenoviral infection. Adoptively transferring adenoviral (Adv) specific T-cells from the donor into the patient may be a promising treatment, but requires the identification of these cells. The aim of the study was to induce Adv-specific cells in response to recently detected pan-DR binding CD4+ T-cell epitopes of adenovirus serotype 5. Epitopes were selected by using a computer algorithm designed to predict HLA pan-DR binding T-cell epitopes. Peripheral blood mononuclear cells (PBMCs) of 26 healthy adults were incubated with 19 different 15-mer peptides. Proliferation expressed as Stimulation Index (SI) was determined. Five peptides with highest SI derived from fiber protein, E1B protein, hexon protein (2 peptides) and DNA-polymerase were selected. To induce Adv-specific T-cells PBMCs from healthy subjects were either cultured with complete inactivated adenovirus for 11 days and restimulated with the different peptides for 3 days (n=10) or directly cultured with the peptides for 7 days (n=10). The cytokine profile induced by these epitopes was determined with multiplex immunoassay (MIA). By using the T-cell capture (TCC) method1 and FACS-sorting it was possible to capture the Adv-specific T-cells for further characterization by PCR and FACS analysis. In comparison with medium and irrelevant Adv-peptides PBMCs cultured with the 5 selected Adv-peptides induced significant larger amounts of Adv-specific CD4+ T-cells and showed a predominant pro-inflammatory cytokine profile. This suggests that peptides are naturally processed. By using TCC Adv-peptide specific CD4+ T-cells were identified and sorted. The Adv-specific T-cells displayed a high expression of TGF-1b, IFNg and Tbet (Th1 response), but also in lesser extent GATA3 and IL10 (Th2 response). A majority of the CD4+ Adv-specific cells expressed perforin and granzyme B, indicating that these CD4+ T-cells play an essential role in adenoviral infections. The induction of a specific immune response to adenovirus and subsequent capture of the Adv-specific T-cells is an important step towards adoptive immunotherapy in case of Adv-infections in the immunocompromised host. Figure 1. Induction of adenoviral specific T-cells (CD4, CTB double positive cells) in response to Adv-peptides. 1A) Induction of CD4+ Adv-specific in response to medium stimulated PBMCs and 1B) in response to a peptide derived from hexon protein. Figure 1. Induction of adenoviral specific T-cells (CD4, CTB double positive cells) in response to Adv-peptides. 1A) Induction of CD4+ Adv-specific in response to medium stimulated PBMCs and 1B) in response to a peptide derived from hexon protein.
33
Sridhar, S., A. Reyes-Sandoval, S. J. Draper, A. C. Moore, S. C. Gilbert, G. P. Gao, J. M. Wilson, and A. V. S. Hill. "Single-Dose Protection against Plasmodium berghei by a Simian Adenovirus Vector Using a Human Cytomegalovirus Promoter Containing Intron A." Journal of Virology 82, no. 8 (February 6, 2008): 3822–33. http://dx.doi.org/10.1128/jvi.02568-07.
Full textAbstract:
ABSTRACT Human adenovirus serotype 5 (AdH5) vector vaccines elicit strong immune responses to the encoded antigen and have been used in various disease models. We designed AdH5 vectors expressing antigen under the control of a human cytomegalovirus (HCMV) immediate-early promoter containing its intron A sequence. The transcriptional levels of antigen and immune responses to antigen for vectors with the HCMV promoter with the intron A sequence (LP) were greater than those for AdH5 vectors using the HCMV promoter sequence without intron A (SP). We compared an E1E3-deleted AdH5 adenoviral vector, which affords more space for insertion of foreign sequences, and showed it to be as immunogenic as an E1-deleted AdH5 vector. Neutralizing antibodies to AdH5 limit the efficacy of vaccines based on the AdH5 serotype, and simian adenoviral vectors offer an attractive option to overcome this problem. We constructed E1E3-deleted human and simian adenoviral vectors encoding the pre-erythrocytic-stage malarial antigen Plasmodium berghei circumsporozoite protein. We compared the immunogenicity and efficacy of AdC6, a recombinant simian adenovirus serotype 6 vector, in a murine malaria model to those of AdH5 and the poxviral vectors MVA and FP9. AdC6 induced sterile protection from a single dose in 90% of mice, in contrast to AdH5 (25%) and poxviral vectors MVA and FP9 (0%). Adenoviral vectors maintained potent CD8+ T-cell responses for a longer period after immunization than did poxviral vectors and mainly induced an effector memory phenotype of cells. Significantly, AdC6 was able to maintain protection in the presence of preexisting immunity to AdH5.
34
Kitazono, Masaki, Vemulkonda Koneti Rao, Rob Robey, Takashi Aikou, Susan Bates, Tito Fojo, and Merrill E. Goldsmith. "Histone deacetylase inhibitor FR901228 enhances adenovirus infection of hematopoietic cells." Blood 99, no. 6 (March 15, 2002): 2248–51. http://dx.doi.org/10.1182/blood.v99.6.2248.
Full textAbstract:
Abstract Adenovirus infection of hematopoietic cells frequently requires high virus concentrations and long incubation times to obtain moderate infection levels because these cells have low levels of Coxsackie and adenovirus receptor (CAR) and αv integrin. The effect of treatment with FR901228 (depsipeptide), a histone deacetylase inhibitor in phase 2 clinical trials, was studied in K562 cells, granulocyte–colony-stimulating factor–mobilized peripheral blood mononuclear cells (PBMCs), and CD34+ peripheral blood stem cells (PBSCs). FR901228 increased CAR and αvintegrin RNA levels and histone H3 acetylation. FR901228 treatment before adenovirus infection was associated with at least a 10-fold increase in transgene expression from a β-galactosidase–expressing adenoviral vector. More than 80% of the PBMCs or CD34+ PBSCs from 7 different donors were β-galactosidase–positive after adenovirus infection with a multiplicity of infection of 10 for 60 minutes. Increased CAR, αv integrin, and acetylated histone H3 levels were observed in PBMCs from a patient treated with FR901228. These studies suggest that FR901228 can increase the efficiency of adenoviral infection in hematopoietic cells.
35
Kühnel, Florian, Bernd Schulte, Thomas Wirth, Norman Woller, Sonja Schäfers, Lars Zender, Michael Manns, and Stefan Kubicka. "Protein Transduction Domains Fused to Virus Receptors Improve Cellular Virus Uptake and Enhance Oncolysis by Tumor-Specific Replicating Vectors." Journal of Virology 78, no. 24 (December 15, 2004): 13743–54. http://dx.doi.org/10.1128/jvi.78.24.13743-13754.2004.
Full textAbstract:
ABSTRACT Expression of cellular receptors determines viral tropism and limits gene delivery by viral vectors. Protein transduction domains (PTDs) have been shown to deliver proteins, antisense oligonucleotides, liposomes, or plasmid DNA into cells. In our study, we investigated the role of several PTD motifs in adenoviral infection. When physiologically expressed, a PTD from human immunodeficiency virus transactivator of transcription (Tat) did not improve adenoviral infection. We therefore fused PTDs to the ectodomain of the coxsackievirus-adenovirus receptor (CARex) to attach PTDs to adenoviral fiber knobs. CARex-Tat and CARex-VP22 allowed efficient adenoviral infection in nonpermissive cells and significantly improved viral uptake rates in permissive cells. Dose-dependent competition of CARex-PTD-mediated infection using CARex and inhibition experiments with heparin showed that binding of CARex-PTD to both adenoviral fiber and cellular glycosaminoglycans is essential for the improvement of infection. CARex-PTD-treated adenoviruses retained their properties after density gradient ultracentrifugation, indicating stable binding of CARex-PTD to adenoviral particles. Consequently, the mechanism of CARex-PTD-mediated infection involves coating of the viral fiber knobs by CARex-PTD, rather than placement of CARex domains on cell surfaces. Expression of CARex-PTDs led to enhanced lysis of permissive and nonpermissive tumor cells by replicating adenoviruses, indicating that CARex-PTDs are valuable tools to improve the efficacy of oncolytic therapy. Together, our study shows that CARex-PTDs facilitate gene transfer in nonpermissive cells and improve viral uptake at reduced titers and infection times. The data suggest that PTDs fused to virus binding receptors may be a valuable tool to overcome natural tropism of vectors and could be of great interest for gene therapeutic approaches.
36
Kasman, Laura, Georgiana Onicescu, and Christina Voelkel-Johnson. "Histone Deacetylase Inhibitors Restore Cell Surface Expression of the Coxsackie Adenovirus Receptor and Enhance CMV Promoter Activity in Castration-Resistant Prostate Cancer Cells." Prostate Cancer 2012 (2012): 1–8. http://dx.doi.org/10.1155/2012/137163.
Full textAbstract:
Adenoviral gene therapy using the death receptor ligand TRAIL as the therapeutic transgene can be safely administered via intraprostatic injection but has not been evaluated for efficacy in patients. Here we investigated the efficacy of adenoviral TRAIL gene therapy in a model of castration resistant prostate cancer and found that intratumoral injections can significantly delay tumor growth but cannot eliminate established lesions. We hypothesized that an underlying cause is inefficient adenoviral delivery. Using the LNCaP progression model of prostate cancer we show that surface CAR expression decreases with increasing tumorigenicity and that castration resistant C4-2b cells were more difficult to transduce with adenovirus than castration sensitive LNCaP cells. Many genes, including CAR, are epigenetically silenced during transformation but a new class of chemotherapeutic agents, known as histone deacetylase inhibitors (HDACi), can reverse this process. We demonstrate that HDACi restore CAR expression and infectivity in C4-2b cells and enhance caspase activation in response to infection with a TRAIL adenovirus. We also show that in cells with high surface CAR expression, HDACi further enhance transgene expression from the CMV promoter. Thus HDACi have multiple beneficial effects, which may enhance not only viral but also non-viral gene therapy of castration resistant prostate cancer.
37
Ogawa, Emiko, W. Mark Elliott, Fiona Hughes, Thomas J. Eichholtz, James C. Hogg, and Shizu Hayashi. "Latent adenoviral infection induces production of growth factors relevant to airway remodeling in COPD." American Journal of Physiology-Lung Cellular and Molecular Physiology 286, no. 1 (January 2004): L189—L197. http://dx.doi.org/10.1152/ajplung.00315.2002.
Full textAbstract:
Previous studies showed an association between latent adenoviral infection with expression of the adenoviral E1A gene and chronic obstructive pulmonary disease (COPD). The present study focuses on how the adenoviral E1A gene could alter expression of growth factors by human bronchial epithelial (HBE) cells. The data show that connective tissue growth factor (CTGF) and transforming growth factor (TGF)-β1 mRNA and protein expression were upregulated in E1A-positive HBE cells. Upregulation of CTGF in this in vitro model was independent of TGF-β secreted into the growth medium. Comparison of E1A-positive with E1A-negative HBE cells showed that both expressed cytokeratin but only E1A-positive cells expressed the mesenchymal markers vimentin and α-smooth muscle actin. We conclude that latent infection of epithelial cells by adenovirus E1A could contribute to airway remodeling in COPD by the viral E1A gene, inducing TGF-β1 and CTGF expression and shifting cells to a more mesenchymal phenotype.
38
Pollack, Alisa, and Rick Varma. "Adenovirus-associated paraphimosis." International Journal of STD & AIDS 30, no. 8 (May 9, 2019): 825–27. http://dx.doi.org/10.1177/0956462419842448.
Full textAbstract:
We present the first reported case of paraphimosis associated with concurrent adenoviral urethritis and conjunctivitis in a heterosexual man. This case reinforces the need to consider adenovirus in the differential diagnosis of non-gonococcal urethritis and describes a potentially serious complication.
39
Benkő, Mária, Péter Élő, Krisztina Ursu, Winfried Ahne, Scott E. LaPatra, Darelle Thomson, and Balázs Harrach. "First Molecular Evidence for the Existence of Distinct Fish and Snake Adenoviruses." Journal of Virology 76, no. 19 (October 1, 2002): 10056–59. http://dx.doi.org/10.1128/jvi.76.19.10056-10059.2002.
Full textAbstract:
ABSTRACT From adenovirus-like viruses originating from a fish and a snake species, a conserved part of the adenoviral DNA polymerase gene was PCR amplified, cloned and sequenced. Phylogenetic analysis showed that the snake adenovirus is closely related to the members of the proposed genus Atadenovirus, whereas the fish isolate seems to represent a separate cluster, likely a new genus.
40
Roy, Soumitra, Yan Zhi, Gary P. Kobinger, Joanita Figueredo, Roberto Calcedo, James R. Miller, Heinz Feldmann, and James M. Wilson. "Generation of an adenoviral vaccine vector based on simian adenovirus 21." Journal of General Virology 87, no. 9 (September 1, 2006): 2477–85. http://dx.doi.org/10.1099/vir.0.81989-0.
Full textAbstract:
Adenoviral vectors can be used to generate potent humoral and cellular immune responses to transgene products. Use of adenoviral vectors based on non-human isolates may allow for their utilization in populations harbouring neutralizing antibodies to common human serotypes. A vector chimera was constructed using simian adenovirus 22 (a serotype belonging to the species Human adenovirus E) and simian adenovirus 21 (a serotype belonging to the species Human adenovirus B) expressing the Ebola (Zaire) virus glycoprotein (Ad C5/C1-ZGP). This chimeric adenovirus vector was used as a model to test its efficacy as a genetic vaccine and comparisons were made to a vector based on the commonly used human adenovirus C serotype 5 (Adhu5-ZGP). Ebola glycoprotein-specific T- and B-cell responses were measured in B10BR mice vaccinated with either Adhu5-ZGP or Ad C5/C1-ZGP vectors. Both vectors resulted in Ebola glycoprotein-specific gamma interferon-expressing T cells, although the Ad C5/C1-ZGP vector appeared to induce lower frequencies with kinetics slower than those elicited by the Adhu5-ZGP vector. The total immunoglobulin G response to Ebola glycoprotein was similar in sera from mice vaccinated with either vector. Two rhesus macaques vaccinated with the Ad C5/C1-ZGP vector were found to mount T-cell and antibody responses to the Ebola glycoprotein. It was found that a single administration of the chimeric Ad C5/C1-ZGP vector protected mice against a lethal challenge with a mouse-adapted strain of the Ebola (Zaire) virus.
41
van Griensven, M., P. Lobenhoffer, A. Barke, T. Tschernig, W. Lindenmaier, C. Krettek, and T. G. Gerich. "Adenoviral gene transfer in a rat fracture model." Laboratory Animals 36, no. 4 (October 1, 2002): 455–61. http://dx.doi.org/10.1258/002367702320389134.
Full textAbstract:
For the enhancement of fracture healing, either purified proteins or vectors for expression of growth factors in situ may be used. Adenoviral vectors directly convert cells to express a transgene. However, the cell types which are preferentially infected and the time of expression during fracture healing are currently not known. The adenoviral type 5 vectors used in this study are replication incompetent viruses, one encoding β-galactosidase (β-GAL) and one green fluorescent protein. Femora of 35 Sprague-Dawley rats were fractured. Three days after stabilization with Kirschner wire, 1012 pfu viral suspension were injected into the fracture zone. As a control, five animals received injections of adenovirus type 2. Animals were sacrificed after 3 days, 1, 2 and 4 weeks. Fractures healed radiographically within 2-3 weeks. All specimens were examined for β-GAL and green fluorescent protein (GFP) expression. Fibroblast and osteoblasts within callus tissue displayed a high transgene expression (week 1). A decrease of expression was observed during the observation period. In this experimental study, we have demonstrated that all cells of the primary callus can be transfected using adenoviral vectors, which provide a tool to further investigate adenoviral transfer of growth factors such as bone morphogenetic protein-2 (BMP-2).
42
Mitsuishi, Michiko, Seiko Masuda, Ichiro Kudo, and Makoto Murakami. "Group V and X secretory phospholipase A2 prevents adenoviral infection in mammalian cells." Biochemical Journal 393, no. 1 (December 12, 2005): 97–106. http://dx.doi.org/10.1042/bj20050781.
Full textAbstract:
sPLA2 (secretory phospholipase A2) enzymes have been implicated in various biological events, yet their precise physiological functions remain largely unresolved. In the present study we show that group V and X sPLA2s, which are two potent plasma membrane-acting sPLA2s, are capable of preventing host cells from being infected with an adenovirus. Bronchial epithelial cells and lung fibroblasts pre-expressing group V and X sPLA2s showed marked resistance to adenovirus-mediated gene delivery in a manner dependent on their catalytic activity. Although adenovirus particles were insensitive to recombinant group V and X sPLA2s, direct addition of these enzymes to 293A cells suppressed both number and size of adenovirus plaque formation. Group V and X sPLA2s retarded the entry of adenovirus into endosomes. Moreover, adenoviral infection was suppressed by LPC (lysophosphatidylcholine), a membrane-hydrolytic product of these sPLA2s. Thus hydrolysis of the plasma membrane by these sPLA2s may eventually lead to the protection of host cells from adenovirus entry. Given that group V and X sPLA2s are expressed in human airway epithelium and macrophages and that the expression of endogenous group V sPLA2 is upregulated by virus-related stimuli in these cells, our present results raise the possibility that group V and X sPLA2s may play a role in innate immunity against adenoviral infection in the respiratory tract.
43
Leen, Ann M., Anne Christin, Mariam Khalil, Heidi Weiss, Adrian P. Gee, Malcolm K. Brenner, Helen E. Heslop, Cliona M. Rooney, and Catherine M. Bollard. "Identification of Hexon-Specific CD4 and CD8 T-Cell Epitopes for Vaccine and Immunotherapy." Journal of Virology 82, no. 1 (October 17, 2007): 546–54. http://dx.doi.org/10.1128/jvi.01689-07.
Full textAbstract:
ABSTRACT Adenoviral infections in the immunocompromised host are associated with significant morbidity and mortality. Although the adoptive transfer of adenovirus-specific T cells may prevent and treat such infections, the T-cell immune response to the multiplicity of adenovirus serotypes and subspecies that infect humans has not been well characterized, impeding the development of such approaches. We have, therefore, analyzed the specificities of T-cell responses to the viral capsid hexon antigen, since this structure is highly conserved in human pathogens. We screened 25 human cytotoxic T-cell lines with adenovirus specificity to extensively characterize their responses to adenoviral hexon and to identify a panel of novel CD4+ and CD8+ T-cell epitopes. Using a peptide library spanning the entire sequence of the hexon protein, we confirmed the responsiveness of these cytotoxic T-cell lines to seven peptides described previously and also identified 33 new CD4- or CD8-restricted hexon epitopes. Importantly, the majority of these epitopes were shared among different adenovirus subspecies, suggesting that T cells with such specificities could recognize and be protective against multiple serotypes, simplifying the task of effective adoptive transfer or vaccine-based immunotherapy for treating infection by this virus.
44
Nicke, Barbara, Min-Jen Tseng, Marycarol Fenrich, and Craig D. Logsdon. "Adenovirus-mediated gene transfer of RasN17 inhibits specific CCK actions on pancreatic acinar cells." American Journal of Physiology-Gastrointestinal and Liver Physiology 276, no. 2 (February 1, 1999): G499—G506. http://dx.doi.org/10.1152/ajpgi.1999.276.2.g499.
Full textAbstract:
CCK stimulates pleiotrophic responses in pancreatic acinar cells; however, the intracellular signaling pathways involved are not well understood. To evaluate the role of the ras gene product in CCK actions, a strategy involving in vitro adenoviral-mediated gene delivery of a dominant-negative mutant Ras (RasN17) was utilized. Isolated acini were infected with various titers of either a control adenovirus or an adenoviral construct expressing RasN17 for 24 h before being treated with CCK. Titer-dependent expression of RasN17 in the acini was confirmed by Western blotting. Infection with control adenovirus [106–109plaque-forming units/mg acinar protein (multiplicity of infection of ∼1–1,000)] had no effect on CCK stimulation of acinar cell amylase release, extracellular-regulated kinase (ERK) or c-Jun kinase (JNK) kinases, or DNA synthesis. In contrast, infection with adenovirus bearing ras N17 increased basal amylase release, inhibited CCK-mediated JNK activation, had no effect on CCK activation of ERK, and inhibited DNA synthesis. These data demonstrate important roles for Ras in specific actions of CCK on pancreatic acinar function.
45
Dunams, Daniela, Payal Sarkar, Wilfred Chen, and Marylynn V. Yates. "Simultaneous Detection of Infectious Human Echoviruses and Adenoviruses by anIn SituNuclease-Resistant Molecular Beacon-Based Assay." Applied and Environmental Microbiology 78, no. 5 (December 22, 2011): 1584–88. http://dx.doi.org/10.1128/aem.05937-11.
Full textAbstract:
ABSTRACTA multiplex methodology using two nuclease-resistant molecular beacons that target specific genomic regions of adenovirus 2 and echovirus 17 during simultaneous infection in A549 cells is presented. Using fluorescence microscopy, visualization of enteroviral and adenoviral replication was possible within 3 h postinfection.
46
Blacklaws, Barbara. "Adenoviral persistence." Trends in Microbiology 6, no. 6 (June 1998): 220. http://dx.doi.org/10.1016/s0966-842x(98)01290-6.
Full text
47
Jhanji, Vishal, Tommy C. Y. Chan, Emmy Y. M. Li, Kanika Agarwal, and Rasik B. Vajpayee. "Adenoviral keratoconjunctivitis." Survey of Ophthalmology 60, no. 5 (September 2015): 435–43. http://dx.doi.org/10.1016/j.survophthal.2015.04.001.
Full text
48
&NA;. "ADENOVIRAL PERICARDITIS." Pediatric Infectious Disease Journal 14, no. 11 (November 1995): 1007–8. http://dx.doi.org/10.1097/00006454-199511000-00019.
Full text
49
Weitzman, Jonathan B. "Adenoviral arrays." Genome Biology 3 (2002): spotlight—20021008–02. http://dx.doi.org/10.1186/gb-spotlight-20021008-02.
Full text
50
Omari, Amro A., and Shahzad I. Mian. "Adenoviral keratitis." Current Opinion in Ophthalmology 29, no. 4 (July 2018): 365–72. http://dx.doi.org/10.1097/icu.0000000000000485.
Full text