Auswahl der wissenschaftlichen Literatur zum Thema „Adenovirus F40“

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Zeitschriftenartikel zum Thema "Adenovirus F40"

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Rajan, Anandi, Elin Palm, Fredrik Trulsson, Sarah Mundigl, Miriam Becker, B. David Persson, Lars Frängsmyr und Annasara Lenman. „Heparan Sulfate Is a Cellular Receptor for Enteric Human Adenoviruses“. Viruses 13, Nr. 2 (14.02.2021): 298. http://dx.doi.org/10.3390/v13020298.

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Human adenovirus (HAdV)-F40 and -F41 are leading causes of diarrhea and diarrhea-associated mortality in children under the age of five, but the mechanisms by which they infect host cells are poorly understood. HAdVs initiate infection through interactions between the knob domain of the fiber capsid protein and host cell receptors. Unlike most other HAdVs, HAdV-F40 and -F41 possess two different fiber proteins—a long fiber and a short fiber. Whereas the long fiber binds to the Coxsackievirus and adenovirus receptor (CAR), no binding partners have been identified for the short fiber. In this study, we identified heparan sulfate (HS) as an interaction partner for the short fiber of enteric HAdVs. We demonstrate that exposure to acidic pH, which mimics the environment of the stomach, inactivates the interaction of enteric adenovirus with CAR. However, the short fiber:HS interaction is resistant to and even enhanced by acidic pH, which allows attachment to host cells. Our results suggest a switch in receptor usage of enteric HAdVs after exposure to acidic pH and add to the understanding of the function of the short fibers. These results may also be useful for antiviral drug development and the utilization of enteric HAdVs for clinical applications such as vaccine development.
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Rafie, K., A. Lenman, J. Fuchs, A. Rajan, N. Arnberg und L. A. Carlson. „The structure of enteric human adenovirus 41—A leading cause of diarrhea in children“. Science Advances 7, Nr. 2 (Januar 2021): eabe0974. http://dx.doi.org/10.1126/sciadv.abe0974.

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Human adenovirus (HAdV) types F40 and F41 are a prominent cause of diarrhea and diarrhea-associated mortality in young children worldwide. These enteric HAdVs differ notably in tissue tropism and pathogenicity from respiratory and ocular adenoviruses, but the structural basis for this divergence has been unknown. Here, we present the first structure of an enteric HAdV—HAdV-F41—determined by cryo–electron microscopy to a resolution of 3.8 Å. The structure reveals extensive alterations to the virion exterior as compared to nonenteric HAdVs, including a unique arrangement of capsid protein IX. The structure also provides new insights into conserved aspects of HAdV architecture such as a proposed location of core protein V, which links the viral DNA to the capsid, and assembly-induced conformational changes in the penton base protein. Our findings provide the structural basis for adaptation of enteric HAdVs to a fundamentally different tissue tropism.
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Pabbaraju, Kanti, Raymond Tellier, Xiao-Li Pang, Jianling Xie, Bonita E. Lee, Linda Chui, Ran Zhuo et al. „A Clinical Epidemiology and Molecular Attribution Evaluation of Adenoviruses in Pediatric Acute Gastroenteritis: a Case-Control Study“. Journal of Clinical Microbiology 59, Nr. 1 (28.10.2020): e02287-20. http://dx.doi.org/10.1128/jcm.02287-20.

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ABSTRACTThe objective of this study was to characterize the etiological role of human adenovirus (HAdV) serotypes in pediatric gastroenteritis. Using a case-control design, we compared the frequencies of HAdV serotypes between children with ≥3 episodes of vomiting or diarrhea within 24 h and <7 days of symptoms (i.e., cases) and those with no infectious symptoms (i.e., controls). Stool samples and/or rectal swabs underwent molecular serotyping with cycle threshold (Ct) values provided by multiplex real-time reverse transcription-PCR testing. Cases without respiratory symptoms were analyzed to calculate the proportion of disease attributed to individual HAdV serotypes (i.e., attributable fraction). Between December 2014 and August 2018, adenoviruses were detected in 18.8% (629/3,347) of cases and 7.2% (97/1,355) of controls, a difference of 11.6% (95% confidence interval [CI], 9.6%, 13.5%). In 96% (95% CI, 92 to 98%) of HAdV F40/41 detections, the symptoms could be attributed to the identified serotype; when serotypes C1, C2, C5, and C6 were detected, they were responsible for symptoms in 52% (95% CI, 12 to 73%). Ct values were lower among cases than among controls (P < 0.001). HAdV F40/41, C2, and C1 accounted for 59.7% (279/467), 17.6% (82/467), and 12.0% (56/467) of all typed cases, respectively. Among cases, Ct values were lower for F40/41 serotypes than for non-F40/41 serotypes (P < 0.001). HAdV F40/41 serotypes account for the majority of HAdV-positive gastroenteritis cases, and when detected, disease is almost always attributed to infection with these pathogens. Non-F40/41 HAdV species have a higher frequency of asymptomatic infection and may not necessarily explain gastroenteritis symptoms. Real-time quantitative PCR may be useful in differentiating asymptomatic shedding from active infection.
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Oliveira, Edson R. A., Lenong Li und Marlene Bouvier. „Intracellular Sequestration of the NKG2D Ligand MIC B by Species F Adenovirus“. Viruses 13, Nr. 7 (01.07.2021): 1289. http://dx.doi.org/10.3390/v13071289.

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The enteric human adenoviruses of species F (HAdVs-F), which comprise HAdV-F40 and HAdV-F41, are significant pathogens that cause acute gastroenteritis in children worldwide. The early transcription unit 3 (E3) of HAdVs-F is markedly different from that of all other HAdV species. To date, the E3 proteins unique to HAdVs-F have not been characterized and the mechanism by which HAdVs-F evade immune defenses in the gastrointestinal (GI) tract is poorly understood. Here, we show that HAdV-F41 infection of human intestinal HCT116 cells upregulated the expression of MHC class I-related chain A (MIC A) and MIC B relative to uninfected cells. Our results also showed that, for MIC B, this response did not however result in a significant increase of MIC B on the cell surface. Instead, MIC B was largely sequestered intracellularly. Thus, although HAdV-F41 infection of HCT116 cells upregulated MIC B expression, the ligand remained inside infected cells. A similar observation could not be made for MIC A in these cells. Our preliminary findings represent a novel function of HAdVs-F that may enable these viruses to evade immune surveillance by natural killer (NK) cells in the infected gut, thereby paving the way for the future investigation of their unique E3 proteins.
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Tahmasebi, Roozbeh, Adriana Luchs, Kaelan Tardy, Philip Michael Hefford, Rory J. Tinker, Owrang Eilami, Flavio Augusto de Padua Milagres et al. „Viral gastroenteritis in Tocantins, Brazil: characterizing the diversity of human adenovirus F through next-generation sequencing and bioinformatics“. Journal of General Virology 101, Nr. 12 (01.12.2020): 1280–88. http://dx.doi.org/10.1099/jgv.0.001500.

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Human enteric adenovirus species F (HAdV-F) is one of the most common pathogens responsible for acute gastroenteritis worldwide. Brazil is a country with continental dimensions where continuous multiregional surveillance is vital to establish a more complete picture of the epidemiology of HAdV-F. The aim of the current study was to investigate the molecular epidemiology of HAdV-F using full-genome data in rural and low-income urban areas in northern Brazil. This will allow a genetic comparison between Brazilian and global HAdV-F strains. The frequency of HAdV-F infections in patients with gastroenteritis and molecular typing of positive samples within this period was also analysed. A total of 251 stool samples collected between 2010 and 2016 from patients with acute gastroenteritis were screened for HAdV-F using next-generation sequencing techniques. HAdV-F infection was detected in 57.8 % (145/251) of samples. A total of 137 positive samples belonged to HAdV-F41 and 7 to HAdV-F40. HAdV-F40/41 dual infection was found in one sample. Detection rates did not vary significantly according to the year. Single HAdV-F infections were detected in 21.9 % (55/251) of samples and mixed infections in 37.4 % (94/251), with RVA/HAdV-F being the most frequent association (21.5 %; 54/251). Genetic analysis indicated that the HAdV-F strains circulating in Brazil were closely related to worldwide strains, and the existence of some temporal order was not observed. This is the first large-scale HAdV-F study in Brazil in which whole-genome data and DNA sequence analyses were used to characterize HAdV-F strains. Expanding the viral genome database could improve overall genotyping success and assist the National Center for Biotechnology Information (NCBI)/GenBank in standardizing the HAdV genome records by providing a large set of annotated HAdV-F genomes.
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Zhang, Ali, Tanner Tessier, Kristianne Galpin, Cason King, Steven Gameiro, Wyatt Anderson, Ahmed Yousef, Wen Qin, Shawn Li und Joe Mymryk. „The Transcriptional Repressor BS69 is a Conserved Target of the E1A Proteins from Several Human Adenovirus Species“. Viruses 10, Nr. 12 (22.11.2018): 662. http://dx.doi.org/10.3390/v10120662.

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Early region 1A (E1A) is the first viral protein produced upon human adenovirus (HAdV) infection. This multifunctional protein transcriptionally activates other HAdV early genes and reprograms gene expression in host cells to support productive infection. E1A functions by interacting with key cellular regulatory proteins through short linear motifs (SLiMs). In this study, the molecular determinants of interaction between E1A and BS69, a cellular repressor that negatively regulates E1A transactivation, were systematically defined by mutagenesis experiments. We found that a minimal sequence comprised of MPNLVPEV, which contains a conserved PXLXP motif and spans residues 112–119 in HAdV-C5 E1A, was necessary and sufficient in binding to the myeloid, Nervy, and DEAF-1 (MYND) domain of BS69. Our study also identified residues P113 and L115 as critical for this interaction. Furthermore, the HAdV-C5 and -A12 E1A proteins from species C and A bound BS69, but those of HAdV-B3, -E4, -D9, -F40, and -G52 from species B, E, D, F, and G, respectively, did not. In addition, BS69 functioned as a repressor of E1A-mediated transactivation, but only for HAdV-C5 and HAdV-A12 E1A. Thus, the PXLXP motif present in a subset of HAdV E1A proteins confers interaction with BS69, which serves as a negative regulator of E1A mediated transcriptional activation.
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Parker, Alan L., John H. McVey, Jessica H. Doctor, Oscar Lopez-Franco, Simon N. Waddington, Menzo J. E. Havenga, Stuart A. Nicklin und Andrew H. Baker. „Influence of Coagulation Factor Zymogens on the Infectivity of Adenoviruses Pseudotyped with Fibers from Subgroup D“. Journal of Virology 81, Nr. 7 (24.01.2007): 3627–31. http://dx.doi.org/10.1128/jvi.02786-06.

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ABSTRACT Recent evidence supports a role for vitamin K-dependent coagulation zymogens in adenovirus serotype 5 (Ad5, subgroup C) infection of hepatocytes. Here, we assessed the effect of virus-zymogen interaction on cellular transduction using a panel of fiber (f)-pseudotyped viruses derived from subgroup D (f47, f33, f24, f45, f17, f30). Each virus directly bound factor X (FX) as determined by surface plasmon resonance, resulting in enhanced cell surface binding. Infection of HepG2 cells was promoted by FX but not by FVII or FIX, while transduction of CHO cells was blocked in heparan sulfate proteoglycan-deficient cells. This suggests a broad role for FX in adenovirus infectivity.
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Mattner, Frauke, Karl-Walter Sykora, Barbara Meissner und Albert Heim. „An Adenovirus Type F41 Outbreak in a Pediatric Bone Marrow Transplant Unit“. Pediatric Infectious Disease Journal 27, Nr. 5 (Mai 2008): 419–24. http://dx.doi.org/10.1097/inf.0b013e3181658c46.

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Rivera-Molina, Yisel, Juan Fueyo, Hong Jiang, Teresa Nguyen, Dong Ho Shin, Gilbert Youssef, Xuejun Fan et al. „EXTH-27. ACTIVATING THE IMMUNITY WITHIN THE TUMOR USING VIROIMMUNOTHERAPY: DELTA-24-RGD ONCOLYTIC ADENOVIRUS ARMED WITH THE IMMUNOPOSITIVE REGULATOR GITRL“. Neuro-Oncology 21, Supplement_6 (November 2019): vi87. http://dx.doi.org/10.1093/neuonc/noz175.359.

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Abstract Based on promising results of recent clinical trials using oncolytic viruses, virotherapy is evolving as an alternative to treat patients with malignant glioma. Our group developed the oncolytic adenovirus Delta-24-RGD (DNX-2401) that is being tested, alone or in combination with anti-PD1, in clinical trials for recurrent glioblastoma (NCT00805376; NCT01956734; NCT02798406). The results suggest that, besides the expected oncolytic effect, the injection of the pathogen initiated, in a subset of patients, an anti-tumoral immunity that led to 20% of long-term survivors (3.5–5 years). To further enhance this effect, we have armed Delta-24-RGD to express the co-stimulatory ligand GITRL, and generated Delta-24-GREAT. The intracranial injection of Delta-24-GREAT prolonged the survival of GL261 glioma-bearing immunocompetent mice when compared to Delta-24-RGD treatment (P=0.002, log-rank test). Delta-24-GREAT treatment resulted in enhanced frequency of tumor-infiltrating lymphocytes: T lymphocytes (CD45+/CD3+) and cytotoxic T lymphocytes (CD45+CD3+CD8+). Functional studies performed by culturing splenocytes from Delta-24-GREAT-treated mice with glioma cells and analyzing secretion of Th1 cytokines, such as IL2 and IFN-γ, showed that lymphocytes recognized not only viral antigens but also tumoral antigens, suggesting the triggering of anti-tumoral immunity. Of interest, Delta-24-GREAT treatment resulted in an antigen-restricted anti-tumor memory effect and in the generation of central immune memory. Thus, rechallenging the survivor mice from the first experiment with a second implantation of glioma cells did not lead to tumor growth, and we detected an increased frequency of central memory CD8+ T cells (CD45+CD62L+). However, survivor mice developed lethal tumors when implanted intracranially with B16/F10 melanoma cells, strongly indicating that the developed immune response was specific for GL261 glioma antigens. This is a novel approach using an oncolytic adenovirus expressing GITRL to target cancer and to stimulate the immunity within the tumor. Our data strongly indicate that this type of strategy may be further developed to treat patients with malignant glioblastoma.
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Kim, Min-Ju, Kyung-Ju Choi, Yoon-A. Kang, Oh-Joon Kwon, Pyung-Hwan Kim, Chae-Ok Yun und Joo-Hang Kim. „850. Concurrent Delivery of GM-CSF and B7-1 Using an Oncolytic Adenovirus Elicits Potent Anti- Tumor Effect on the Growth Established B16-F10 Tumor Model“. Molecular Therapy 13 (2006): S328. http://dx.doi.org/10.1016/j.ymthe.2006.08.936.

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Dissertationen zum Thema "Adenovirus F40"

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Rabe, Nasim Estelle. „Evaluation and performance comparison between two commercial multiplex gastroenteritis diagnostic systems in a routine laboratory setting“. Thesis, Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-447123.

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Abstract Background: Gastroenteritis is a common infection and the leading cause of morbidity worldwide and is mostly caused by viruses. Outbreaks appear in both developed and developing countries and result in large economic costs. Rapid detection is important for appropriate treatment, control and to prevent the spread of infection.  Objective: Evaluation and performance comparison between the BioFire®FilmArray® Torch System gastrointestinal panel and the Molecular BD MAXTMenteric viral panel to indicate a multiplex method for viral gastroenteritis diagnostic in a routine laboratory setting.  Material and methods: In this study, 58 different samples were used which consisted of selected stool specimens from patients who were tested and treated for gastroenteritis infection at Uppsala Academic Hospital and Norrlands University Hospital in Umeå during 2018-2021, samples from Quality control for molecular diagnostics viral gastroenteritis EQA pilot study during 2018-2019 and cultivated strains of different adenovirus species from 2018. All samples were analyzed with both systems for comparison of detected pathogens.  Results: Sensitivity and specificity values were 95% and 100% respectively for the BioFire®FilmArray®Torch System and 100% and 93.3% for the BD MAXTMSystem.   Conclusions: Bothsystems are rapid and adequate diagnostic tools. The BioFire®FilmArray®Torch System with greater coverage has the ability of detecting more pathogens and is more promising particularly in the occasional infection circumstance. The BD MAXTMSystem demonstrated almost the same results and seems to be a better option in times of an outbreak when the numbers of patients are significantly higher.
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Thoma, Clemens Matthias Manuel. „Improving intraperitoneal adenovirus virotherapy for ovarian cancer“. Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:841e4334-f408-4da3-b8e6-1d29350c5304.

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The use of intraperitoneal (i.p.) adenovirus virotherapy of ovarian cancer is currently limited by insufficient efficacy and high toxicity. Both factors are associated with adenovirus serotype 5 (Ad5) in this setting and may be serotype-specific. Low levels of uptake receptors (CAR and αV integrins) on ovarian tumour cells and widespread immunity against Ad5 among patients appear to restrict efficacy and intraperitoneal inflammatory responses against Ad5 were among the reasons for the termination of a phase II/III clinical trial in ovarian cancer. This thesis sought to overcome these obstacles by investigating the alternative adenovirus serotypes Ad3 and Ad11. For these viruses lower pre-existing antiviral immunity and utilisation of different uptake receptors have been reported. Furthermore, virus cloaking with novel polymers which could impart enhanced protection from neutralisation was examined. In vitro, wild-type Ad3, Ad5 and Ad11 displayed differential oncolytic activity in a panel of ovarian cancer cell lines which partly correlated to uptake receptor expression and virus internalisation. However, some cell lines displayed lysis resistance in a serotype-specific manner. While the inflammatory response six hours after i.p. administration of Ad11 in CD46-transgenic mice did not differ from Ad5, in long-term studies of repeated administration Ad5 induced significantly more severe pathologic effects in the form of adhesions and liver toxicity than Ad11 or mock-treatment. Oncolysis inhibition assays using malignant exudate samples demonstrated greater neutralisation of Ad3 and Ad5 in comparison to Ad11 at low concentrations of samples. Notably, 10-fold less Ad11 than Ad5 was required for oncolytic efficacy at a sample concentration of 10%. In an ex vivo model of ascites from ovarian cancer patients Ad5 modified with novel polymer formulations achieved at least 50% cell kill in six of eight samples, in contrast to two of eight samples for non-modified Ad5. These data suggest that virotherapy using Ad11 might be advantageous over Ad3 or Ad5. The lack of strong inflammation and the possibility to decrease treatment doses due to less neutralisation of Ad11 might result in considerably improved patient safety. Chemical modification of Ad with novel polymers presents an exciting advancement in overcoming treatment neutralisation in adenovirus virotherapy.
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