Academic literature on the topic 'Animal model of infection'
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Journal articles on the topic "Animal model of infection"
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Zak, O., and T. O'Reilly. "Animal infection models and ethics--the perfect infection model." Journal of Antimicrobial Chemotherapy 31, suppl D (January 1, 1993): 193–205. http://dx.doi.org/10.1093/jac/31.suppl_d.193.
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Han, Mingyuan, Charu Rajput, Tomoko Ishikawa, Caitlin Jarman, Julie Lee, and Marc Hershenson. "Small Animal Models of Respiratory Viral Infection Related to Asthma." Viruses 10, no. 12 (December 1, 2018): 682. http://dx.doi.org/10.3390/v10120682.
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Respiratory viral infections are strongly associated with asthma exacerbations. Rhinovirus is most frequently-detected pathogen; followed by respiratory syncytial virus; metapneumovirus; parainfluenza virus; enterovirus and coronavirus. In addition; viral infection; in combination with genetics; allergen exposure; microbiome and other pathogens; may play a role in asthma development. In particular; asthma development has been linked to wheezing-associated respiratory viral infections in early life. To understand underlying mechanisms of viral-induced airways disease; investigators have studied respiratory viral infections in small animals. This report reviews animal models of human respiratory viral infection employing mice; rats; guinea pigs; hamsters and ferrets. Investigators have modeled asthma exacerbations by infecting mice with allergic airways disease. Asthma development has been modeled by administration of virus to immature animals. Small animal models of respiratory viral infection will identify cell and molecular targets for the treatment of asthma.
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Glupczynski, Y., and A. Burette. "Animal model of Helicobacter pylori infection." Antimicrobial Agents and Chemotherapy 34, no. 7 (July 1, 1990): 1462. http://dx.doi.org/10.1128/aac.34.7.1462.
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Janitschke, Klaus, A. Julio Martinez, Govinda S. Visvesvara, and Frederick Schuster. "Animal Model Balamuthia Mandrillaris CNS Infection." Journal of Neuropathology and Experimental Neurology 55, no. 7 (July 1996): 815–21. http://dx.doi.org/10.1097/00005072-199607000-00006.
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Haenle, Maximilian, Carmen Zietz, Tobias Lindner, Kathleen Arndt, Anika Vetter, Wolfram Mittelmeier, Andreas Podbielski, and Rainer Bader. "A Model of Implant-Associated Infection in the Tibial Metaphysis of Rats." Scientific World Journal 2013 (2013): 1–8. http://dx.doi.org/10.1155/2013/481975.
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Objective. Implant-associated infections remain serious complications in orthopaedic and trauma surgery. A main scientific focus has thus been drawn to the development of anti-infective implant coatings. Animal models of implant-associated infections are considered helpful in thein vivotesting of new anti-infective implant coatings. The aim of the present study was to evaluate a novel animal model for generation of implant-associated infections in the tibial metaphysis of rats.Materials and Methods. A custom-made conical implant made of Ti6Al4V was inserted bilaterally at the medial proximal tibia of 26 female Sprague-Dawley rats.Staphylococcus aureusin amounts spanning four orders of magnitude and each suspended in 15 μl phosphate buffered saline (PBS) was inoculated into the inner cavity of the implant after the implantation into the defined position. Controls were treated accordingly with PBS alone. Animals were then followed for six weeks until sacrifice. Implant-associated infection was evaluated by microbiological investigation using swabs and determination of viable bacteria in the bone around the implant and the biofilm on the implants after sonification.Results. Irrespective of the initial inoculum, all animals in the various groups harbored viable bacteria in the intraoperative swabs as well as the sonication fluid of the implant and the bone samples. No correlation could be established between initially inoculated CFU and population sizes on implant surfaces at sacrifice. However, a significantly higher viable count was observed from peri-implant bone samples for animals inoculated with 106 CFU. Macroscopic signs of animal infection (pus and abscess formation) were only observed for implants inoculated with at least 105 CFUS. aureus.Discussion/Conclusion. The results demonstrate the feasibility of this novel animal model to induce an implant-associated infection in the metaphysis of rats, even with comparatively low bacterial inocula. The specific design of the implant allows an application of bacteria in reproducible numbers at well-defined contact sites to the animal bone.
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Iyer, Rajiv R., Noah Gorelick, Karen Carroll, Ari M. Blitz, Sarah Beck, Caroline M. Garrett, Audrey Monroe, et al. "Evaluation of an in vivo model for ventricular shunt infection: a pilot study using a novel antimicrobial-loaded polymer." Journal of Neurosurgery 131, no. 2 (August 2019): 587–95. http://dx.doi.org/10.3171/2018.1.jns172523.
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OBJECTIVEVentricular shunt infection remains an issue leading to high patient morbidity and cost, warranting further investigation. The authors sought to create an animal model of shunt infection that could be used to evaluate possible catheter modifications and innovations.METHODSThree dogs underwent bilateral ventricular catheter implantation and inoculation with methicillin-sensitive Staphylococcus aureus (S. aureus). In 2 experimental animals, the catheters were modified with a polymer containing chemical “pockets” loaded with vancomycin. In 1 control animal, the catheters were polymer coated but without antibiotics. Animals were monitored for 9 to 11 days, after which the shunts were explanted. MRI was performed after shunt implantation and prior to catheter harvest. The catheters were sonicated prior to microbiological culture and also evaluated by electron microscopy. The animals’ brains were evaluated for histopathology.RESULTSAll animals underwent successful catheter implantation. The animals developed superficial wound infections, but no neurological deficits. Imaging demonstrated ventriculitis and cerebral edema. Harvested catheters from the control animal demonstrated > 104 colony-forming units (CFUs) of S. aureus. In the first experimental animal, one shunt demonstrated > 104 CFUs of S. aureus, but the other demonstrated no growth. In the second experimental animal, one catheter demonstrated no growth, and the other grew trace S. aureus. Brain histopathology revealed acute inflammation and ventriculitis in all animals, which was more severe in the control.CONCLUSIONSThe authors evaluated an animal model of ventricular shunting and reliably induced features of shunt infection that could be microbiologically quantified. With this model, investigation of pathophysiological and imaging correlates of infection and potentially beneficial shunt catheter modifications is possible.
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Kenney, Scott P., and Xiang-Jin Meng. "Hepatitis E Virus: Animal Models and Zoonosis." Annual Review of Animal Biosciences 7, no. 1 (February 15, 2019): 427–48. http://dx.doi.org/10.1146/annurev-animal-020518-115117.
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Hepatitis E virus (HEV) is an important human pathogen that historically has been difficult to study. Limited levels of replication in vitro hindered our understanding of the viral life cycle. Sporadic and low-level virus shedding, lack of standardized detection methods, and subclinical infections made the development of animal models difficult. Better diagnostic techniques and understanding of the virus increased our ability to identify and characterize animal strains and animals that are amenable to model human-relevant infection. These advances are translating into the development of useful HEV animal models so that some of the greatest concerns associated with HEV infection, including host immunology, chronic infection, severe pregnancy mortality, and extrahepatic manifestations, can now be studied. Continued development of these animal models will be instrumental in understanding the many complex questions associated with HEV infection and for assessing therapeutics and prevention strategies to minimize HEV becoming a greater risk to the human population.
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Shimamura, Tsuyoshi, Nobuo Kubota, and Kazutoshi Shibuya. "Animal Model of Dermatophytosis." Journal of Biomedicine and Biotechnology 2012 (2012): 1–11. http://dx.doi.org/10.1155/2012/125384.
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Dermatophytosis is superficial fungal infection caused by dermatophytes that invade the keratinized tissue of humans and animals. Lesions from dermatophytosis exhibit an inflammatory reaction induced to eliminate the invading fungi by using the host’s normal immune function. Many scientists have attempted to establish an experimental animal model to elucidate the pathogenesis of human dermatophytosis and evaluate drug efficacy. However, current animal models have several issues. In the present paper, we surveyed reports about the methodology of the dermatophytosis animal model for tinea corporis, tinea pedis, and tinea unguium and discussed future prospects.
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Groseth, Allison, Don Gardner, Kimberly Meade-White, Susanne Amler, and Hideki Ebihara. "Immunocompetent hamsters as a model for orthobunyavirus-induced neuroinvasion and neuropathology." PLOS Neglected Tropical Diseases 17, no. 5 (May 26, 2023): e0011355. http://dx.doi.org/10.1371/journal.pntd.0011355.
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Background Bunyavirus infections, including those caused by Bunyamwera serogroup orthobunyaviruses, represent a significant and yet likely still vastly underappreciated cause of mild to moderate human febrile infections. In severe cases, these infections can also cause neurological disease, particularly meningitis and encephalitis, and infection can even be fatal. However, with a few exceptions, information regarding the mechanisms underlying the neuroinvasion and neuropathogenesis of such infections is limited. This is due in part to a lack of animal models to facilitate such studies. Methodology/Principal findings In an effort to develop an immunocompetent model of infection with Bunyamwera serogroup orthobunyaviruses, we infected 4-6-week-old female hamsters via either the intraperitoneal or subcutaneous route with 106 pfu/animal of Bunyamwera virus (BUNV), Batai virus or Ngari virus. Only BUNV infection resulted in clinical disease, which was characterized by weight loss, lethargy and neurological signs (i.e. tremor of the head or limbs, loss of righting reflex, “waltzing”). While symptoms were of similar severity for both routes, they occurred more frequently following subcutaneous inoculation. Consistent with these clinical signs, both antigen staining and histopathological abnormalities were found extensively throughout the brain. Conclusions/Significance The reported hamster model of BUNV infection provides a new tool for studying orthobunyavirus infection, and particularly neuroinvasion and the development of neuropathology. This model is particularly significant because it makes use of immunologically competent animals and relies on a subcutaneous inoculation route that more closely mimics the natural infection route for arboviruses, thereby providing a more authentic cellular and immunological context at the initial site of infection.
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TSUKIYAMA-KOHARA, Kyoko, and Michinori KOHARA. "Animal model for hepatitis C virus infection." Uirusu 65, no. 2 (2015): 255–62. http://dx.doi.org/10.2222/jsv.65.255.
Full textDissertations / Theses on the topic "Animal model of infection"
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Maglennon, G. A. "Study of papillomavirus latent infection in an animal model." Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1306763/.
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Papillomaviruses cause a wide spectrum of benign and neoplastic diseases in humans and animals. They may also cause infections that are characterised by the absence of clinical signs of disease and some of these may represent viral latency. Many viruses have a latent stage of their life cycle and papillomaviruses appear to be no different. For example, some low-risk human papillomavirus types such as HPV-11 and HPV-6 can cause infections that resemble latency. It has recently been shown that rabbit oral papillomavirus (ROPV) is an appropriate model of these virus types. Infection of the tongue mucosa with ROPV leads to the formation of benign papillomas that form and regress within a matter of weeks. In this thesis, we show that ROPV is a suitable model system for the study of latent papillomavirus infections. The regression of ROPV papillomas is followed by the persistence of viral DNA and RNA in the absence of clinical signs of disease. Persistence of ROPV DNA is generally restricted to basal epithelial cells at sites of previous infection. Low copy numbers of viral DNA in the basal layer are compatible with infection remaining in only a subset of these cells (possibly epithelial stem cells). Typically there is no amplification of viral DNA in the upper layers of the epithelium. ROPV proteins are undetectable during latency suggesting that the productive stages of the life cycle are not completed. Low levels of ROPV early transcripts are detectable and it is possible that early proteins are necessary to allow stable maintenance of viral episomes in basal epithelial cells. We attempt to demonstrate the ability of latent ROPV infection to reactivate to form clinical disease. Evidence of spontaneous reactivation was seen on one occasion, but efforts to initiate reactivation by immunosuppressing rabbits were hampered by the toxicity of the drugs used. However, our preliminary data suggest that immunosuppression of rabbits can cause reactivation of latent ROPV.
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Wen, Li. "Immune responses to vaginal viral infection in a mouse model." Thesis, The University of Sydney, 1998. https://hdl.handle.net/2123/27666.
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Viral infection in the female reproductive tract is a global health problem, with high morbidity and mortality worldwide. However, immune protection of the female reproductive tract against virus infection is poorly understood. The aim of the study described in this thesis was to investigate the immune responses to vaginal West Nile virus (WNV) infection in an experimental mouse model, in an attempt to characterize the immune mechanisms involved in protecting the host against viral infection in the female genital tract. WNV is a neurotropic flavivirus which can infect both humans and animals, and which belongs to a virus family causing serious disease throughout the world. The mouse model of genital tract infection with WNV is not representative of the human situation; nevertheless, such models may be an appropriate tool to identify virus antigen components which may be effective in
eliciting protective immunity at the genital mucosal surface.
The progesterone-dominated mouse model is mainly used in the experiments of the present study. This model impairs the vaginal epithelial barrier, increasing the susceptibility of adult mice to vaginal virus infection. Virus-infected cells were detected in the vaginal epithelium of BALB/c mice from day 2 to day 7 after infection by immunoperoxidase labelling of WNV protein. A series of immune responses were evoked following vaginal WNV infection. Specific anti-WNV IgM and IgG antibodies were detected in vaginal washing by ELISA, associated with an increasing lgM and IgG containing cell infiltration, and a significant B220+ B cell infiltration in the vaginal mucosa. A correlated accumulation of B220+ B cells in the iliac lymph nodes (ILN) was detected by flow cytometry. B cells presented a major
cell population infiltrating in the vagina and proliferation in the ILN indicates that humoral immunity plays an important role against vaginal WNV infection. Locally produced IgG is the major antibody contributing to anti-WNV responses to infection in the vagina. The role of cellular immunity to protect animal against vaginal WNV infection was also examined in this study. The expression of major histocompatibility complex class II (MHC-II) molecules in the vaginal mucosa was upregulated after infection, which suggests the possibility that interferon-y (IFN-y) participates in the immune response, since MHC-11 expression is increased by IFN-Y· The infiltration of CD4 helper T cells (Th cells) and CD8 (cytotoxic lymphocytes [CTL]) in the vagina were also significant increased after infection.
These responses were coincident with a significant proliferation of CD4 and CD8 T cells from day 3 after infection. These results suggest IFN-y, CD4 T cells play an important role against WNV vaginal infection. ICAM-1, VCAM-1 and
CD44 adhesion molecules were involved in response to infection. Upregulation expression of ICAM-1 and CD44, and a de novo induction of VCAM-1 expression in the vagina were detected after virus infection, and these responses paralleled the infiltration of immune cells in the vagina.
Such responses were significantly accelerated and of greater magnitude in intravaginal (IVAG) immune, intraperitoneal (i.p.) immune and intradermal (i.d.) immune mice after intravaginal challenge with WNV, and this immunity completely protected animals against subsequent vaginal infection. Unexpectedly, the immune responses in i.d. immune mice were much stronger than IVGA immune mice. Moreover, there was a markedly higher CD4 and CD8 T cell infiltration and VCAM-1 expression in the vaginal mucosa, a significantly higher proliferation of CD4 and CD8 T cells in ILN, and a similar B220 B cell infiltration in the vagina and proliferation in the ILN. This suggests that i.d. immunization may be a possible route to induce immunity for prevention of vaginal viral infection.
The role of IL-5 in host immunity to vaginal WNV infection was investigated by using IL-5 gene knockout (GKO) mice. It was found that IL-5 GKO mice were more susceptible to WNV vaginal infection. Thus, infected cells could be detected in vagina epithelium earlier and remained for a longer duration than in normal control mice. The susceptibility of GKO mice to vaginal WNV infection correlated with delayed specific anti-WNV IgM and lgG antibodies in vaginal washings, lower numbers of IgG-containing plasma cell infiltrating the vagina, and a significantly lower B220 B cell and CD8 T cell infiltrate at certain time points compared normal control mice. However, a significant CD4 T cell infiltration and significant upregulation of expression of ICAM-1, VCAM-1 and MHC-II molecules in the vaginal mucosa at the later stage of infection, implies a compensatory mechanism may exist. The expression of IL-4 mRNA in the vaginal mucosa was enhanced after virus infection, coincident with the detection of specific anti-WNV lgG, suggesting that IL-4 contributed to specific antibody production and thus contributes to the eradication of WNV vaginal infection.
In this study, it was found that BALB/c mice are more susceptible to WNV vaginal infection than C57BL/6 mice, since the mortality to WNV vaginal infection in BALB/c mice was 10-fold higher than C57BL/6, and WNV-infected cells were detected in vaginal epithelium from day 2 to day 7 after infection in BALB/c mice, while these cells could only be detected on day 5 after infection in C57BL/6 mice. The susceptibility of BALB/c mice to WNV vaginal infection correlated with a markedly lower B220 B cell and CD8 T cell infiltration in the vagina of this strain
than in C57BL/6 mice. These results indicate that immune responses to vaginal WNV infection is genetically determined, varying in different mouse strains.
In a pilot experiment, the oestrogen-dominated model was used to compare immunity to intravaginal WNV infection in animals with a different hormonal status. Oestrogen-dominated mice were refractory to vaginal infection, but such resistance gave no protection against secondary virus challenge in the progesterone phase.
These mice presented a similar pattern of epithelial cell infection as progesterone dominated naive mice in primary infection, though the infiltration of B220 B cells and CD8 T cells in the vagina of these mice was higher than in progesterone dominated naive mice after infection, and the proliferation of total lymphocytes and CD8 T cells in ILN of these mice was also higher than in progesterone-dominated naive mice in the early course of the infection. Interestingly, the infiltration of CD4+ T cells in the vagina of virus-challenged progesterone phase immune mice was significant higher than oestrogen phase immune mice after rechallenge, and the proliferation of total lymphocytes, B220 B cells and CD8 T cells in ILN of the former was higher than latter at day 1 after challenge. These results suggest that the weaker and different profile of immunity initiated in the oestrogen phase does not produce full protection against secondary vaginal challenge.
The results from this study provides basic information about immune responses to vaginal virus infection and as such may contribute to the long-term development of vaccines to prevent the sexual transmission of viruses.
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Shrief, Raghdaa. "Surrogate Markers of Infection Suitable for Monitoring Infectious Burden in Animal Models of Aspergillosis." Thesis, University of Manchester, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.525921.
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Shanmuganathan, Subathra Devi. "The woodchuck as an animal model for the study of the immune response in hepadna virus infection." Thesis, University College London (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298130.
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CARRARO, MONICA. "Identification of infection biomarkers in a murine model of pneumonia by Streptococcus pneumoniae." Doctoral thesis, Università di Siena, 2018. http://hdl.handle.net/11365/1037742.
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Streptococcus pneumoniae infections remain a public health problem despite the availability of vaccines. In order to study alternative preventive strategies it is essential to have a reliable animal model of the infection. To date, the majority of vaccine efficacy evaluation studies still rely on direct read-outs such as the survival rate after challenge and the CFU counts in blood and in the lungs. A murine model of lung infection was developed in which animal death was not the endpoint: clinical parameters, cellular lung infiltrate and systemic immune response were evaluated in (i) infected mice, (ii) vaccinated mice, and (iii) vaccinated and challenged mice. All these parameters were used to identify biomarkers of sublethal pneumonia and protection following vaccination with the pneumococcal conjugate vaccine.
Female C57BL/6 mice were infected with different doses of S. pneumoniae strain TIGR4, the dose of 1.6 x 107 CFUs was capable to induce measurable signs of the disease with a 100% survival and was therefore used for subsequent experiments. Histological examination and flow cytometry analysis of the lung tissue were performed at different time-points after bacterial inoculation. Data revealed that absolute numbers of the cell populations evaluated through flow cytometry were significantly different 7 days after the infection from those of uninfected mice, and histological evaluation of the lungs at this time-point also revealed the presence of leukocyte infiltrate. The presence of the infiltrate represented a biomarker of infection. When mice were vaccinated prior to pneumococcal challenge, they showed no weight loss and a mild infiltrate in the lungs. The absence of the infiltrate in relation with mild clinical signs and a good humoral response defined the protected phenotype.
The type of immune response mounting following interaction of the immune system with S. pneumoniae was evaluated using mice splenocytes re-stimulated in vitro with inactivated TIGR4. The production of 23 cytokines was measured, revealing that splenocytes started to react to in vitro re-stimulation at 4 days after infection and peaking 7 days after infection. A predominant production of IFN-γ and IL-17 was observed in infected mice, while this profile was skewed to Th2 characteristic cytokines such as IL-4 and IL-5 when mice had received the vaccine. These features, together with cellular infiltrates observed in the lungs, can be considered biomarkers of protection that could be used to study the protection induced by a vaccine candidate using parameters other than the survival rates and the CFU counts.
We identified measurable and reliable biomarkers of pneumococcal pneumonia that could be investigated in vaccine efficacy studies and could become tools to develop new immunization strategies against S. pneumoniae.
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Shen, Hong. "Hepatitis C infection models." Thesis, Paris 5, 2012. http://www.theses.fr/2012PA05T016.
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L'hépatite C (VHC) est l'une des causes principales de maladies du foie dans le monde, qui représentent un risque élevé d'évoluer vers la cirrhose et le carcinome hépatocellulaire. Actuellement, le traitement standard de l’infection par le VHC est l'interféron pégylé-(peg-IFN) et la ribavirine. Bien que le taux de la réponse virale soutenue (RVS) au traitement se soit améliorée au cours de ces années, cette thérapie n'est pas efficace chez tous les patients. En outre, plusieurs effets secondaires toxiques, de complications et le coût élevé limitent la compliance du patient et l'efficacité du traitement. Il n'existe pas de modèle simple d'infection par le VHC et il est nécessaire de développer des modèles in vitro et in vivo utiles pour étudier la physiopathologie de l'infection par le VHC, y compris les événements précoces de l'infection aiguë (l'entrée du virus, des mécanismes immunologiques et génétiques prédictifs) ainsi que l'évaluation de la puissance des médicaments antiviraux contre le VHC. Nous rapportons ici, nos efforts visant à développer des modèles appropriés de l'infection par le VHC. Dans un premier temps, nous avons établi un modèle de petit animal pour étudier l'infection par le VHC. Tupaia est un petit animal, apparenté aux primates et peu couteux. Dans notre travail, nous avons étudié la susceptibilité du tupaia à l'infection par VHC. Douze tupaias adultes ont été inoculés avec le VHC provenant de sérum de patient et d'ARN du VHC (génotype 1a). Trois jeunes tupaias ont été artificiellement nourris pendant un mois et ensuite inoculés par le VHC provenant de sérum du patient. L'ARN du VHC, les anticorps anti-VHC et l’évolution des quasi-espèces du VHC ont été déterminées chez l'animal avant et après l'inoculation. L'infection transitoire et intermittente s'est produite chez deux des 3 jeunes tupaias et l’infection chronique par le VHC s’est produite chez quatre tupaias sur 12 tupaias adultes. Le tupaia devrait représenter un modèle utile pour l'étude de l’infection chronique par le VHC. Dans une deuxième étape, un système de culture in vitro d'hépatocytes primaires de Tupaia a été établi, dans lequel l'infection par le VHC ne pouvait être bloquée ni par le CD81 soluble ni par des anticorps dirigés contre le CD81. Pour comprendre ces résultats, nous avons cloné, séquencé la grande boucle extracellulaire (LEL) du CD81 chez le Tupaia et analysé l'interaction de la protéine d’enveloppe E2 du VHC avec la LEL du CD81 chez le Tupaia par un test « enzyme-linked immunosorbent assay » (EIA). Nous avons constaté que chez le Tupaia, la séquence d'acides aminés du LEL de CD81 qui se lie au VHC présentait en 6 résidus d'acides aminés différents par rapport à la séquence humaine et la capacité de LEL de CD81 à se lier à la proteine d’enveloppe E2 du VHC a également diminuée. La structure différente de CD81 chez l’homme et chez le tupaia pourrait expliquer l'altération de l'interaction entre CD81 et la proteine E2 du VHC. Ce résultat démontre un rôle important de LEL du CD81 pour l'entrée du VHC. Dans une troisième étape, nous avons développé un modèle ex vivo de culture de tranches de foie humain et leur infection par le VHC. Le développement de lignées cellulaires provenant d’hepatocarcinome, permissives à la réplication du VHC, a fourni d'importants nouveaux outils virologiques pour étudier les mécanismes de l'infection par le VHC, mais ce modèle expérimental reste relativement éloigné des conditions physiologiques et pathologiques. Nous rapportons ici le développement d'un nouveau modèle ex vivo utilisant la culture de tranches de foie humain adulte, démontrant, pour la première fois, la capacité d’isolats primaires ainsi que JFH -1, H77/C3, Con1/C3 (HCVcc), de répliquer et de produire de novo des particules virales infectieuses ayant un titre viral élevé…Hepatitis C virus (HCV) is one of the major causes of liver disease all over the world which has a high risk to progress to cirrhosis and hepatocellular carcinoma. Currently, the licensed standard treatment of HCV infection is Pegylated-interferon (peg-IFN) and ribavirin. Although the sustained viral response (SVR) rate of treatment has improved during these years, this therapy is not effective in all patients. In addition, several toxic side effects, complication and high cost limit the patient compliance and the efficacy of the treatment. There is no easy model of HCV infection and it is necessary to develop useful in vitro and in vivo models to study the pathobiology of HCV infection, including early events of acute infection (viral entry, immunological mechanisms, and genetic predictors) as well as the evaluation of the potency of the HCV antiviral drugs. We report here in our efforts in developing suitable models of HCV infection. In a first step, we preliminary established a small animal model to study HCV infection. Tupaia is a small, closed related to primate and cost-effective animal. In our work, we investigated the susceptibly of tupaia to HCV infection. Twelve adult tupaias were inoculated with native HCV from patient serum and full-length HCV RNA (Genotype 1a). Three young tupaias were artificially breeded for a month and then inoculated by native HCV from patient serum. HCV RNA, anti-HCV and HCV quasi species evolution were determined in the animal before and after inoculation. Transient and intermittent infection occurred in two among 3 young tupaias and HCV chronic infection occurred in four among 12 adult tupaias. Tupaia should represent a useful model for study HCV chronic infection. In a second step, an in vitro culture system of primary tupaia hepatocytes has been established in which HCV infection could be blocked neither by the soluble CD81 nor by antibodies against CD81. To understand these results, we cloned, sequenced the large extracellular loop (LEL) of tupaia CD81 and analyzed the interaction of HCV E2 with the tupaia CD81 LEL by enzyme-linked immunosorbent assay (EIA). We found that in the tupaia the amino acids sequence of HCV CD81 LEL presented in 6 different amino acid residues compared with human CD81 LEL sequence and the CD81 LEL ability to bind to HCV E2 was also decreased. The different structure of CD81 between human and tupaia could explain the alteration of the interaction between HCV E2 and CD81. This result demonstrated an important role of CD81 LEL for HCV entry. In a third step, we developed an ex vivo model of human liver slices culture and their infection with HCV. The development of human cultured HCV-replication-permissive hepatocarcinoma cell lines has provided important new virological tools to study the mechanisms of HCV infection; however this experimental model remains distantly related to physiological and pathological conditions. Here, we report the development of a new ex vivo model using human adult liver slices culture, demonstrating, for the first time, the ability of primary isolates to undergo de novo viral replication with the production of high titer infectious virus, as well as JFH-1, H77/C3, Con1/C3 (HCVcc). This experimental model was validated by demonstrating the HCV neutralization or HCV inhibition, in a dose-dependent manner, either by CD81 or E2 specific antibodies or convalescent serum from a recovered HCV patient, or by anti-viral drugs. This new ex vivo model represents a powerful tool for studying the viral life cycle, dynamics of virus spread in the liver and also for evaluating the efficacy of the new antiviral drugs. In the last step, we evaluated the efficacy of the new antiviral drugs with our ex vivo model of human adult liver slices. HCV NS3/4A protease is essential for viral replication and has been one of the most important target for developing specific antiviral drug
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Furr, Patricia Mary. "The development and value of animal models of mycoplasmal infection." Thesis, Open University, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.358598.
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Peterson, Christopher. "Evaluation of Therapeutics for an Enterovirus 71 Infection in an AG129 Mouse Model." DigitalCommons@USU, 2018. https://digitalcommons.usu.edu/etd/7278.
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Discovered in 1969 in California, enterovirus 71 (EV-71) is a serious cause of disease in young children. It is one of the major causative agents of hand, food, and mouth disease (HFMD), and can produce neurological complications, such as meningitis, encephalitis, and an acute flaccid paralysis. For serious cases, the fatality rate can be up to 26%, almost exclusively in young children.
While the virus was initially discovered in the United States, it was soon detected in the Eastern hemisphere, causing outbreaks in Europe and Asia. The largest outbreak occurred in Taiwan in 2008, with approximately 490,000 cases and 128 fatalities. However, despite the seriousness of EV-71, there are currently no approved antiviral treatments. Physicians rely on supportive care and the off-label use of a purified antibody mixture, intravenous immunoglobulin, for treatment.
Part of the difficulty in developing antivirals for EV-71 is a lack of drug testing in animal models. Animal testing is a crucial step in drug development, determining which compounds will progress to clinical trials in humans. However, viruses that cause disease in humans do not necessarily cause disease or the same type of disease in animals. As such, viruses often need to be adapted before they can cause disease in their animal hosts. Adaption isn’t always successful and can result in a virus that produces disease that is unlike that seen in humans. Furthermore, some animal models can produce disease only under a strict set of conditions, such as newborn mice. Sometimes these animal model conditions may be impractical for testing potential treatments.
At the Institute for Antiviral Research (IAR), we developed an animal model for EV-71 in four-week-old AG129 mice. AG129 mice lack the alpha, beta, and gamma interferon receptors, making them immunocompromised. Being immunocompromised, these mice are more susceptible to infection, including infection from human viruses. In our model, EV-71 infection produces neurological signs, including a rear-limb paralysis (similar to the paralysis seen children with EV-71). The virus is also lethal in these animals, which provides an observable and consistent baseline for evaluating potential drugs.
We assessed twenty-four potential treatments in our EV-71 model. Two compounds, STF434 and STF1019, provided 30% and 87% protection against mortality. Intravenous immunoglobulin was also examined and found to be about 50% protective against mortality, depending on the dose and time of administration. Intravenous immunoglobulin also reduced inflammatory modulators (cytokines) in the brain and spinal cord. We consider this to be highly relevant, given that inflammation is a serious component of EV-71 infection.
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Xi, Jin [Verfasser], and Thomas [Akademischer Betreuer] Iftner. "An Out-bred Animal Model of Cottontail Rabbit Papillomavirus Latent Infection / Jin Xi ; Betreuer: Thomas Iftner." Tübingen : Universitätsbibliothek Tübingen, 2019. http://d-nb.info/1197610812/34.
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Clasper, Jonathan Charles. "Secondary intramedullary nailing of the tibia in an animal model of an external fixator pin track infection." Thesis, University of Southampton, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268414.
Full textBooks on the topic "Animal model of infection"
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Axel, Schmidt, and Weber Olaf F, eds. Animal testing in infectiology. Basel: Karger, 2001.
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Ann, Salzman Lois, ed. Animal models of retrovirus infection and their relationship to AIDS. Orlando: Academic Press, 1986.
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Johnson-Delaney, Cathy A. Simian & human retroviruses in nonhuman primates: Infection, disease & animal model studies : a bibliography, 1988-1989 annual update. Seattle, Wash: Primate Information Center, Regional Primate Research Center, University of Washington, 1989.
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Johnson-Delaney, Cathy A. Simian & human retroviruses in nonhuman primates: Infection, disease & animal model studies : a bibliography, 1989-1990 annual update. Seattle, Wash: Primate Information Center, Regional Primate Research Center, University of Washington, c1990., 1990.
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Johnson-Delaney, Cathy A. Simian & human retroviruses in nonhuman primates: Infection, disease & animal model studies : a bibliography, 1988-1989 annual update. Seattle, Wash: Primate Information Center, Regional Primate Research Center, University of Washington, 1989.
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Ann, Salzman Lois, ed. Animalmodels of retrovirus infection and their relationship to AIDS. Orlando: Academic Press, 1986.
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R, Swearengen James, ed. Biodefense: Research methodology and animal models. Boca Raton, Fla: Taylor & Francis, 2006.
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Johnson-Delaney, Cathy A. Simian and human retroviruses in nonhuman primates: Infection, disease and animal model studies : a bibliography, 1991-1992 annual update. Seattle, Wash: Primate Information Center, Regional Primate Research Center, University of Washington, 1993.
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Johnson-Delaney, Cathy A. Simian and human retroviruses in nonhuman primates: Infection, disease and animal model studies : a bibliography, 1992-1993 annual update. Seattle, Wash: Primate Information Center, Regional Primate Research Center, University of Washington, 1994.
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Johnson-Delaney, Cathy A. Simian and human retroviruses in nonhuman primates: Infection, disease and animal model studies : a bibliography, 1990-1991 annual update. Seattle: Primate Information Center, Regional Primate Research Center, University of Washington, 1991.
Find full textBook chapters on the topic "Animal model of infection"
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Sharma, Karun, Babita Shashni, Meena K. Sakharkar, Kishore R. Sakharkar, and Ramesh Chandra. "Animal Model of Cancer and Infection." In Post-genomic Approaches in Cancer and Nano Medicine, 85–100. New York: River Publishers, 2022. http://dx.doi.org/10.1201/9781003339083-4.
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Calabro, Lorenzo, Cameron Lutton, Ahmed Fouad Seif El Din, R. Geoff Richards, and T. Fintan Moriarty. "Animal Models of Orthopedic Implant-Related Infection." In Biomaterials Associated Infection, 273–304. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4614-1031-7_12.
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Li, Huoming, and Hao Li. "Animal Models of Tuberculosis." In Vaccines for Neglected Pathogens: Strategies, Achievements and Challenges, 139–70. Cham: Springer International Publishing, 2023. http://dx.doi.org/10.1007/978-3-031-24355-4_7.
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AbstractTuberculosis (TB) is an important zoonotic disease caused by infection with Mycobacterium tuberculosis (Mtb) complex and has a significant impact on public health. Animal models are suitable tools to mimic the clinical symptoms observed in human TB and provide an opportunity to understand immune responses to infection and the pathophysiology and pathogenesis of TB. In this chapter, we summarize the animal models that are used in Mtb research, including common models such as the mouse, rat, guinea pig, non-human primates, rabbit, cattle and zebrafish, as well as discuss some newly established animal models.
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Bergin, Ingrid L., and James G. Fox. "Animal Models of Helicobacter pylori Infection." In Helicobacter pylori Infection and Immunity, 215–51. Boston, MA: Springer US, 2002. http://dx.doi.org/10.1007/978-1-4615-0681-2_13.
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Leinonen, M., and P. Saikku. "Animal models for Chlamydia pneumoniae infection." In Chlamydia pneumoniae and Chronic Diseases, 19–24. Berlin, Heidelberg: Springer Berlin Heidelberg, 2000. http://dx.doi.org/10.1007/978-3-642-57195-4_4.
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Lee, Ju Yup. "Animal Models of H. pylori Infection." In Helicobacter pylori, 537–46. Singapore: Springer Singapore, 2016. http://dx.doi.org/10.1007/978-981-287-706-2_55.
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Harvill, Eric T., and Tracy Nicholson. "Animal models." In Pertussis, 100–111. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780198811879.003.0006.
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There is a long history of the study of Bordetella species in animal hosts, built on the foundation of Koch’s postulates: experimentally inoculating animals with virulent bacteria to define various pathogenic outcomes. Inoculation of mice, rats, pigs, baboons, and humans simulate whooping cough with increasing accuracy, albeit with exponentially increasing costs and difficulties. While most of the basic processes of immune activation and pathogenesis are quite similar from rodents to primates, relative to other pathogen infection systems there are marked differences that are important to consider. While most of this work has involved B. pertussis, the closely related species B. bronchiseptica naturally, and highly efficiently, infects a variety of animals, allowing aspects of pathogenesis to be examined in the context of natural infections. More recently, the ongoing transmission of B. pertussis within highly vaccinated populations has increased interest in understanding the nature of the transmission process. Several innovative animal models have now been established that allow transmission of B. bronchiseptica among mice, rabbits, and pigs, and transmission of B. pertussis among baboons. Together, these animal model systems have taught us most of what we know of the nature of the complex interactions within an individual host, transmission between hosts, and the past and ongoing evolution of these species. Recent and ongoing improvements of the historical animal infection systems, and the generation of new experimental infection systems to study pathogenesis and transmission, are critical to advance our understanding and control of the resurgence of this highly infectious disease.
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Gudmundsson, S., and H. Erlendsdóttir. "Murine Thigh Infection Model." In Handbook of Animal Models of Infection, 137–44. Elsevier, 1999. http://dx.doi.org/10.1016/b978-012775390-4/50154-8.
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Zimmerli, W. "Tissue Cage Infection Model." In Handbook of Animal Models of Infection, 409–17. Elsevier, 1999. http://dx.doi.org/10.1016/b978-012775390-4/50186-x.
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Matsumoto, Tetsuro. "Rat Bladder Infection Model." In Handbook of Animal Models of Infection, 447–51. Elsevier, 1999. http://dx.doi.org/10.1016/b978-012775390-4/50191-3.
Full textConference papers on the topic "Animal model of infection"
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Zulaziz, N., A. Azhim, H. Miyazaki, M. Kinoshita, N. Himeno, D. Saitoh, and Y. Morimoto. "A novel animal model for subcutaneous soft tissue infection using temporally neutropenic lys-EGFP mice." In 2015 10th Asian Control Conference (ASCC). IEEE, 2015. http://dx.doi.org/10.1109/ascc.2015.7244500.
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Legostaev, S. S., E. V. Protopopova, R. Yu Lutkovsky, and V. A. Svyatchenko. "STUDY OF THE EFFECTS OF SARS-COV-2 CO-INFECTION WITH A NON-PATHOGENIC VARIANT OF THE COXSACKIE A7 VIRUS (LEV-8 STRAIN) AND ENTEROVIRUS 71." In X Международная конференция молодых ученых: биоинформатиков, биотехнологов, биофизиков, вирусологов и молекулярных биологов — 2023. Novosibirsk State University, 2023. http://dx.doi.org/10.25205/978-5-4437-1526-1-256.
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The paper presents the results of the study of the effects of co-infection of SARS-CoV-2 with non-pathogenic for humans strain LEV-8 (live enterovirus vaccine) of Coxsackie virus A7 and enterovirus 71 (EV71) on the model of cell cultures and laboratory animals. In vitro experiments showed that during infection enteroviruses and SARS-CoV-2 have a competitive inhibitory effect on each other, with a more pronounced degree of suppression of SARS-CoV-2. Modeling of SARS-CoV-2 co-infection with enteroviruses in laboratory animals showed that preliminary infection with enteroviruses leads to a pronounced inhibition of SARS-CoV-2 replication in the lungs of co-infected animals and a faster release of the lower respiratory tract from infectious SARS-CoV-2 virus, as well as to a decrease in the severity of clinical manifestations of coronavirus infection. The results obtained indicate that the studied enteroviruses have a pronounced interfering activity during co-infection, which manifests itself in a sharp inhibition of the infectious activity of SARS-CoV-2.
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Tanwar, A., R. Chawla, M. Basu, R. Arora, and HA Khan. "FRI0032 Curative effect of camellia sinensis (CS) against opportunistic infection in vulnerable animal model of rheumatoid arthritis." In Annual European Congress of Rheumatology, 14–17 June, 2017. BMJ Publishing Group Ltd and European League Against Rheumatism, 2017. http://dx.doi.org/10.1136/annrheumdis-2017-eular.1057.
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Zhu, Banghe, Caitlin Guenther, Sunkuk Kwon, Eva M. Sevick-Muraca, and Junghae Suh. "Using molecular imaging to assess the delivery and infection of protease activated virus in animal model of myocardial infarction." In SPIE BiOS, edited by Guillermo J. Tearney, Kenton W. Gregory, and Laura Marcu. SPIE, 2017. http://dx.doi.org/10.1117/12.2256760.
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Willett, Nick J., M. Alice Li, Brent A. Uhrig, Gordon L. Warren, and Robert E. Guldberg. "Muscle Injury Attenuates BMP-2 Mediated Tissue Regeneration in a Novel Rat Model of Composite Bone and Muscle Injury." In ASME 2011 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2011. http://dx.doi.org/10.1115/sbc2011-53589.
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Musculoskeletal diseases and injuries are a major burden on society, representing the most common cause of pain and impaired function worldwide. Composite injuries involving bone and the surrounding soft tissue comprise one of the most challenging musculoskeletal conditions to return to normal function. During repair of these injuries there is a loss of the synergistic interactions between adjacent tissues resulting in impaired bone regeneration. Additionally, local soft tissue ischemia may also be a contributing factor to increased infection rates observed in severe composite tissue injuries. Muscle has been implicated as a source for re-vascularization, osteoprogenitor cells and osteogenic factors, as well as a contributor to the biomechanical stimuli; however, associated studies have mostly been qualitative in nature, offering little insight into the mechanistic nature of the relationship of soft tissue to bone regeneration. Small animal models of critically sized bone defects are an efficient means to test engraftment strategies of novel constructs and therapeutics particularly in terms of functional restoration of a limb. Our lab previously developed a critically-sized rat segmental defect model with which we have quantitatively assessed bone regeneration using numerous constructs and therapeutic treatments [1]. Our objective was to develop a composite injury model by combining this segmental defect model with a muscle injury adjacent to the bone defect. We hypothesized that animals with a composite injury would have attenuated BMP-2 mediated tissue regeneration as compared to animals with a single tissue injury.
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Altizer, Sonia M. "Monarchs as a model system for studying animal migration and infectious diseases." In 2016 International Congress of Entomology. Entomological Society of America, 2016. http://dx.doi.org/10.1603/ice.2016.88949.
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Cui, X., W. Xu, D. J. Pepper, J. Sun, J. Welsh, and P. Eichacker. "The Effects of Obesity on Outcome in Preclinical Animal Models of Infection and Sepsis: A Systematic Review and Meta-Analysis." In American Thoracic Society 2019 International Conference, May 17-22, 2019 - Dallas, TX. American Thoracic Society, 2019. http://dx.doi.org/10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a1698.
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Noval, Noval, Ali Rakhman Hakim, and Ahmad Irawan. "Antipyretic Effects of (phaleria macrocarpa (scheff) boerl.) Infusa In Mice Galur Wistar As Animal Model." In 2nd Sari Mulia International Conference on Health and Sciences 2017 (SMICHS 2017) � One Health to Address the Problem of Tropical Infectious Diseases in Indonesia. Paris, France: Atlantis Press, 2017. http://dx.doi.org/10.2991/smichs-17.2017.44.
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Bauer, Carla M., Caleb C. Zavitz, Kristen N. Lambert, Earl G. Brown, Karen L. Mossman, and Martin R. Stämpfli. "Treating Viral Exacerbations Of COPD With Steroids: Lessons Learned From Animal Models Of Cigarette Smoke Exposure And Influenza A Virus Infection." In American Thoracic Society 2010 International Conference, May 14-19, 2010 • New Orleans. American Thoracic Society, 2010. http://dx.doi.org/10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a1016.
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Padilo, Larisa P., Onega V. Ulianova, Galina Maslyakova, Alla Bucharskaya, Sergey Dobdin, Irina Subbotina, Anatoly Skripal, et al. "Can the infection, caused by Chlamydia psittaci, produce the stimulation of the growth of a malignant tumor: studying by using t-LASCA technique on animal model." In Saratov Fall Meeting 2019: Optical and Nano-Technologies for Biology and Medicine, edited by Valery V. Tuchin and Elina A. Genina. SPIE, 2020. http://dx.doi.org/10.1117/12.2563841.
Full textReports on the topic "Animal model of infection"
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Wang, Xinrun, Tianye Li, Xuechai Bai, Yun Zhu, and Meiliang Zhang. Therapeutic prospect on umbilical cord mesenchymal stem cells in animal model with primary ovarian insufficiency: A meta-analysis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, May 2023. http://dx.doi.org/10.37766/inplasy2023.5.0075.
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Review question / Objective: Participants: experiment POI animal models; Interventions: human umbilical cord mesenchymal stem cells; Comparisons: POI animal models without hUCMSC therapy; Outcomes: estrous cycle situation, serum sex hormone level and ovarian follicle count; Studies: randomized controlled animal study; The aim of the review is to figure out whether hUCMSC can recover ovarian function in POI animal models. Condition being studied: Primary ovarian insufficiency (POI) is a syndrome characterized by reduced or absent ovarian function (hypogonadism) and elevated levels of gonadotropins, specifically luteinising hormone (LH) and follicle-stimulating hormone (FSH). Etiologies of POI are various. Genetic disorders, autoimmune diseases, iatrogenic injuries like chemotherapy and radiotherapy, and infectious diseases all contribute to the development of POI. Main manifestation of POI includes decreased ovarian function and infertility. Patients may suffer from menopausal symptoms, such as increased cardiovascular disease, decreased bone mineral density, vulvovaginal atrophy, psychological distress and so on. Current treatment of POI is limited. HRT mainly ameliorates symptoms while ART can achieve fertility in some patients but faces many challenges in clinical practice because it's hard to get satisfied oocytes. Stem cell therapy is proved to be efficient in recovering organ functions and hUCMSC is one of the easiest cell to obtain. So we think hUCMSC is promising in treating POI.
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Splitter, Gary A., Menachem Banai, and Jerome S. Harms. Brucella second messenger coordinates stages of infection. United States Department of Agriculture, January 2011. http://dx.doi.org/10.32747/2011.7699864.bard.
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Aim 1: To determine levels of this second messenger in: a) B. melitensiscyclic-dimericguanosinemonophosphate-regulating mutants (BMEI1448, BMEI1453, and BMEI1520), and b) B. melitensis16M (wild type) and mutant infections of macrophages and immune competent mice. (US lab primary) Aim 2: To determine proteomic differences between Brucelladeletion mutants BMEI1453 (high cyclic-dimericguanosinemonophosphate, chronic persistent state) and BMEI1520 (low cyclicdimericguanosinemonophosphate, acute virulent state) compared to wild type B. melitensisto identify the role of this second messenger in establishing the two polar states of brucellosis. (US lab primary with synergistic assistance from the Israel lab Aim 3: Determine the level of Brucellacyclic-dimericguanosinemonophosphate and transcriptional expression from naturally infected placenta. (Israel lab primary with synergistic assistance from the US lab). B. Background Brucellaspecies are Gram-negative, facultative intracellular bacterial pathogens that cause brucellosis, the most prevalent zoonosis worldwide. Brucellosis is characterized by increased abortion, weak offspring, and decreased milk production in animals. Humans are infected with Brucellaby consuming contaminated milk products or via inhalation of aerosolized bacteria from occupational hazards. Chronic human infections can result in complications such as liver damage, orchitis, endocarditis, and arthritis. Brucellaspp. have the ability to infect both professional and non-professional phagocytes. Because of this, Brucellaencounter varied environments both throughout the body and within a cell and must adapt accordingly. To date, few virulence factors have been identified in B. melitensisand even less is known about how these virulence factors are regulated. Subsequently, little is known about how Brucellaadapt to its rapidly changing environments, and how it alternates between acute and chronic virulence. Our studies suggest that decreased concentrations of cyclic dimericguanosinemonophosphate (c-di-GMP) lead to an acute virulent state and increased concentrations of c-di-GMP lead to persistent, chronic state of B. melitensisin a mouse model of infection. We hypothesize that B. melitensisuses c-di-GMP to transition from the chronic state of an infected host to the acute, virulent stage of infection in the placenta where the bacteria prepare to infect a new host. Studies on environmental pathogens such as Vibrio choleraeand Pseudomonas aeruginosasupport a mechanism where changes in c-di-GMP levels cause the bacterium to alternate between virulent and chronic states. Little work exists on understanding the role of c-di-GMP in dangerous intracellular pathogens, like Brucellathat is a frequent pathogen in Israeli domestic animals and U.S. elk and bison. Brucellamust carefully regulate virulence factors during infection of a host to ensure proper expression at appropriate times in response to host cues. Recently, the novel secondary signaling molecule c-di-GMP has been identified as a major component of bacterial regulation and we have identified c-di-GMP as an important signaling factor in B. melitensishost adaptation. C. Major conclusions, solutions, achievements 1. The B. melitensis1453 deletion mutant has increased c-di-GMP, while the 1520 deletion mutant has decreased c-di-GMP. 2. Both mutants grow similarly in in vitro cultures; however, the 1453 mutant has a microcolony phenotype both in vitro and in vivo 3. The 1453 mutant has increased crystal violet staining suggesting biofilm formation. 4. Scanning electron microscopy revealed an abnormal coccus appearance with in increased cell area. 5. Proteomic analysis revealed the 1453 mutant possessed increased production of proteins involved in cell wall processes, cell division, and the Type IV secretion system, and a decrease in proteins involved in amino acid transport/metabolism, carbohydrate metabolism, fatty acid production, and iron acquisition suggesting less preparedness for intracellular survival. 6. RNAseq analysis of bone marrow derived macrophages infected with the mutants revealed the host immune response is greatly reduced with the 1453 mutant infection. These findings support that microlocalization of proteins involved in c-di-GMP homeostasis serve a second messenger to B. melitensisregulating functions of the bacteria during infection of the host.
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Shpigel, Nahum, Raul Barletta, Ilan Rosenshine, and Marcelo Chaffer. Identification and characterization of Mycobacterium paratuberculosis virulence genes expressed in vivo by negative selection. United States Department of Agriculture, January 2004. http://dx.doi.org/10.32747/2004.7696510.bard.
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Mycobacterium avium subsp. paratuberculosis (MAP) is the etiological agent of a severe inflammatory bowel disease (IBD) in ruminants, known as Johne’s disease or paratuberculosis. Johne’s disease is considered to be one of the most serious diseases affecting dairy cattle both in Israel and worldwide. Heavy economic losses are incurred by dairy farmers due to the severe effect of subclinical infection on milk production, fertility, lower disease resistance and early culling. Its influence in the United States alone is staggering, causing an estimated loss of $1.5 billion to the agriculture industry every year. Isolation of MAP from intestinal tissue and blood of Crohn's patients has lead to concern that it plays a potential pathogenic role in promoting human IDB including Crohn’s disease. There is great concern following the identification of the organism in animal products and shedding of the organism to the environment by subclinically infected animals. Little is known about the molecular basis for MAP virulence. The goal of the original proposed research was to identify MAP genes that are required for the critical stage of initial infection and colonization of ruminants’ intestine by MAP. We proposed to develop and use signature tag mutagenesis (STM) screen to find MAP genes that are specifically required for survival in ruminants upon experimental infection. This research projected was approved as one-year feasibility study to prove the ability of the research team to establish the animal model for mutant screening and alternative in-vitro cell systems. In Israel, neonatal goat kids were repeatedly inoculated with either one of the following organisms; MAP K-10 strain and three transposon mutants of K-10 which were produced and screened by the US PI. Six months after the commencement of inoculation we have necropsied the goats and taken multiple tissue samples from the jejunum, ileum and mesenteric lymph nodes. Both PCR and histopathology analysis indicated on efficient MAP colonization of all the inoculated animals. We have established several systems in the Israeli PI’s laboratory; these include using IS900 PCR for the identification of MAP and using HSP65-based PCR for the differentiation between MAV and MAP. We used Southern blot analysis for the differentiation among transposon mutants of K-10. In addition the Israeli PI has set up a panel of in-vitro screening systems for MAP mutants. These include assays to test adhesion, phagocytosis and survival of MAP to/within macrophages, assays that determine the rate of MAPinduced apoptosis of macrophages and MAP-induced NO production by macrophages, and assays testing the interference with T cell ã Interferon production and T cell proliferation by MAP infected macrophages (macrophage studies were done in BoMac and RAW cell lines, mouse peritoneal macrophages and bovine peripheral blood monocytes derived macrophages, respectively). All partners involved in this project feel that we are currently on track with this novel, highly challenging and ambitious research project. We have managed to establish the above described research systems that will clearly enable us to achieve the original proposed scientific objectives. We have proven ourselves as excellent collaborative groups with very high levels of complementary expertise. The Israeli groups were very fortunate to work with the US group and in a very short time period to master numerous techniques in the field of Mycobacterium research. The Israeli group has proven its ability to run this complicated animal model. This research, if continued, may elucidate new and basic aspects related to the pathogenesis MAP. In addition the work may identify new targets for vaccine and drug development. Considering the possibility that MAP might be a cause of human Crohn’s disease, better understanding of virulence mechanisms of this organism might also be of public health interest as well.
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Ficht, Thomas, Gary Splitter, Menachem Banai, and Menachem Davidson. Characterization of B. Melinensis REV 1 Attenuated Mutants. United States Department of Agriculture, December 2000. http://dx.doi.org/10.32747/2000.7580667.bard.
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Brucella Mutagenesis (TAMU) The working hypothesis for this study was that survival of Brucella vaccines was directly related to their persistence in the host. This premise is based on previously published work detailing the survival of the currently employed vaccine strains S19 and Rev 1. The approach employed signature-tagged mutagenesis to construct mutants interrupted in individual genes, and the mouse model to identify mutants with attenuated virulence/survival. Intracellular survival in macrophages is the key to both reproductive disease in ruminants and reticuloendothelial disease observed in most other species. Therefore, the mouse model permitted selection of mutants of reduced intracellular survival that would limit their ability to cause reproductive disease in ruminants. Several classes of mutants were expected. Colonization/invasion requires gene products that enhance host-agent interaction or increase resistance to antibacterial activity in macrophages. The establishment of chronic infection requires gene products necessary for intracellular bacterial growth. Maintenance of chronic infection requires gene products that sustain a low-level metabolism during periods characterized little or no growth (1, 2). Of these mutants, the latter group was of greatest interest with regard to our originally stated premise. However, the results obtained do not necessarily support a simplistic model of vaccine efficacy, i.e., long-survival of vaccine strains provides better immunity. Our conclusion can only be that optimal vaccines will only be developed with a thorough understanding of host agent interaction, and will be preferable to the use of fortuitous isolates of unknown genetic background. Each mutant could be distinguished from among a group of mutants by PCR amplification of the signature tag (5). This approach permitted infection of mice with pools of different mutants (including the parental wild-type as a control) and identified 40 mutants with apparently defective survival characteristics that were tentatively assigned to three distinct classes or groups. Group I (n=13) contained organisms that exhibited reduced survival at two weeks post-infection. Organisms in this group were recovered at normal levels by eight weeks and were not studied further, since they may persist in the host. Group II (n=11) contained organisms that were reduced by 2 weeks post infection and remained at reduced levels at eight weeks post-infection. Group III (n=16) contained mutants that were normal at two weeks, but recovered at reduced levels at eight weeks. A subset of these mutants (n= 15) was confirmed to be attenuated in mixed infections (1:1) with the parental wild-type. One of these mutants was eliminated from consideration due to a reduced growth rate in vitro that may account for its apparent growth defect in the mouse model. Although the original plan involved construction of the mutant bank in B. melitensis Rev 1 the low transformability of this strain, prevented accumulation of the necessary number of mutants. In addition, the probability that Rev 1 already carries one genetic defect increases the likelihood that a second defect will severely compromise the survival of this organism. Once key genes have been identified, it is relatively easy to prepare the appropriate genetic constructs (knockouts) lacking these genes in B. melitensis Rev 1 or any other genetic background. The construction of "designer" vaccines is expected to improve immune protection resulting from minor sequence variation corresponding to geographically distinct isolates or to design vaccines for use in specific hosts. A.2 Mouse Model of Brucella Infection (UWISC) Interferon regulatory factor-1-deficient (IRF-1-/- mice have diverse immunodeficient phenotypes that are necessary for conferring proper immune protection to intracellular bacterial infection, such as a 90% reduction of CD8+ T cells, functionally impaired NK cells, as well as a deficiency in iNOS and IL-12p40 induction. Interestingly, IRF-1-/- mice infected with diverse Brucella abortus strains reacted differently in a death and survival manner depending on the dose of injection and the level of virulence. Notably, 50% of IRF-1-/- mice intraperitoneally infected with a sublethal dose in C57BL/6 mice, i.e., 5 x 105 CFU of virulent S2308 or the attenuated vaccine S19, died at 10 and 20 days post-infection, respectively. Interestingly, the same dose of RB51, an attenuated new vaccine strain, did not induce the death of IRF-1-/- mice for the 4 weeks of infection. IRF-1-/- mice infected with four more other genetically manipulated S2308 mutants at 5 x 105 CFU also reacted in a death or survival manner depending on the level of virulence. Splenic CFU from C57BL/6 mice infected with 5 x 105 CFU of S2308, S19, or RB51, as well as four different S2308 mutants supports the finding that reduced virulence correlates with survival Of IRF-1-/- mice. Therefore, these results suggest that IRF-1 regulation of multi-gene transcription plays a crucial role in controlling B. abortus infection, and IRF-1 mice could be used as an animal model to determine the degree of B. abortus virulence by examining death or survival. A3 Diagnostic Tests for Detection of B. melitensis Rev 1 (Kimron) In this project we developed an effective PCR tool that can distinguish between Rev1 field isolates and B. melitensis virulent field strains. This has allowed, for the first time, to monitor epidemiological outbreaks of Rev1 infection in vaccinated flocks and to clearly demonstrate horizontal transfer of the strain from vaccinated ewes to unvaccinated ones. Moreover, two human isolates were characterized as Rev1 isolates implying the risk of use of improperly controlled lots of the vaccine in the national campaign. Since atypical B. melitensis biotype 1 strains have been characterized in Israel, the PCR technique has unequivocally demonstrated that strain Rev1 has not diverted into a virulent mutant. In addition, we could demonstrate that very likely a new prototype biotype 1 strain has evolved in the Middle East compared to the classical strain 16M. All the Israeli field strains have been shown to differ from strain 16M in the PstI digestion profile of the omp2a gene sequence suggesting that the local strains were possibly developed as a separate branch of B. melitensis. Should this be confirmed these data suggest that the Rev1 vaccine may not be an optimal vaccine strain for the Israeli flocks as it shares the same omp2 PstI digestion profile as strain 16M.
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Yogev, David, Ricardo Rosenbusch, Sharon Levisohn, and Eitan Rapoport. Molecular Pathogenesis of Mycoplasma bovis and Mycoplasma agalactiae and its Application in Diagnosis and Control. United States Department of Agriculture, April 2000. http://dx.doi.org/10.32747/2000.7573073.bard.
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Mycoplasma bovis and M. agalactiae are two phylogenetically related mycoplasmas which cause economically significant diseases in their respective bovine or small ruminant hosts. These organisms cause persistent asymptomatic infections that can result in severe outbreaks upon introduction of carrier animals into susceptible herds. Little is known about the mechanisms underlying mycoplasma-host interaction, variation in virulence, or of the factors enabling avoidance of the host immune system. In recent years it has become apparent that the ability of pathogenic microorganisms to rapidly alter surface antigenic structures and to fine tune their antigenicity, a phenomena called antigenic variation, is one of the most effective strategies used to escape immune destruction and to establish chronic infections. Our discovery of a novel genetic system, mediating antigenic variation in M. bovis (vsp) as well as in M. agalactiae (avg) served as a starting point for our proposal which included the following objectives: (i) Molecular and functional characterization of the variable surface lipoproteins (Vsp) system of M. bovis and comparison with the Vsp-counterpart in M. agalactiae (ii) Determination of the role of Vsp proteins in the survival of M. bovis when confronted by host defense factors, (iii) Assessment of Vsp-based genetic and antigenic typing of M. bovis and M. agalactiae for epidemiology of infection and (iv) Improvement of diagnostic tests for M. bovis and M. agalactiae based on the vsp-and vsp-analogous systems. We have carried out an extensive molecular characterization of the vsp system and unravelled the precise molecular mechanism responsible for the generation of surface antigenic variation in M. bovis. Our data clearly demonstrated that the two pathogenic mycoplasma species possess large gene families encoding variable lipoprotein antigens that apparently play an important role in immune evasion and in pathogen-host interaction during infection. Phase variable production of these antigens was found to be mediated by a novel molecular mechanism utilizing double site-specific DNA inversions via an intermediate vsp configuration. Studies in model systems indicate that phase variation of VspA is relevant in interaction between M. bovis and macrophages or monocytes, a crucial stage in pathogenesis. Using an ELISA test with captured VspA as an antigen, phase variation was shown to occur in vivo and under field conditions. Genomic rearrangements in the avg gene family of M. agalactiae were shown to occur in vivo and may well have a role in evasion of host defences and establishment of chronic infection. An epidemiological study indicated that patterns of vsp-related antigenic variation diverge rapidly in an M. bovis infected herd. Marked divergence was also found with avg-based genomic typing of M. agalactiae in chronically infected sheep. However, avg-genomic fingerprints were found to be relatively homogeneous in different animals during acute stages of an outbreak of Contagious Agalactiae, and differ between unrelated outbreaks. These data support the concept of vsp-based genomic typing but indicate the necessity for further refinement of the methodology. The molecular knowledge on these surface antigens and their encoding genes provides the basis for generating specific recombinant tools and serological methods for serodiagnosis and epidemiological purposes. Utilization of these methods in the field may allow differentiating acutely infected herds from chronic herds and disease-free herds. In addition the highly immunogenic nature of these lipoproteins may facilitate the design of protective vaccine against mycoplasma infections.
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Chejanovsky, Nor, and Bruce A. Webb. Potentiation of Pest Control by Insect Immunosuppression. United States Department of Agriculture, January 2010. http://dx.doi.org/10.32747/2010.7592113.bard.
Full textAbstract:
The restricted host range of many baculoviruses, highly pathogenic to Lepidoptera and non-pathogenic to mammals, limits their use to single or few closely related Lepidopteran species and is an obstacle to extending their implementation for pest control. The insect immune response is a major determinant of the ability of an insect pathogen to efficiently multiply and propagate. We have developed an original model system to study the Lepidopteran antiviral immune response based on Spodoptera littoralis resistance to AcMNPV (Autographa californica multiple nucleopolyhedrovirus) infection and the fascinating immunosuppressive activity of polydnaviruses .Our aim is to elucidate the mechanisms through which the immunosuppressive insect polydnaviruses promote replication of pathogenic baculoviruses in lepidopteran hosts that are mildly or non-permissive to virus- replication. In this study we : 1- Assessed the extent to which and the mechanisms whereby the immunosuppressive Campoletis sonorensis polydnavirus (CsV) or its genes enhanced replication of a well-characterized pathogenic baculovirus AcMNPV, in polydnavirus-immunosuppressedH. zea and S. littoralis insects and S. littoralis cells, hosts that are mildly or non-permissive to AcMNPV. 2- Identified CsV genes involved in the above immunosuppression (e.g. inhibiting cellular encapsulation and disrupting humoral immunity). We showed that: 1. S. littoralis larvae mount an immune response against a baculovirus infection. 2. Immunosuppression of an insect pest improves the ability of a viral pathogen, the baculovirus AcMNPV, to infect the pest. 3. For the first time two PDV-specific genes of the vankyrin and cystein rich-motif families involved in immunosuppression of the host, namely Pvank1 and Hv1.1 respectively, enhanced the efficacy of an insect pathogen toward a semipermissive pest. 4. Pvank1 inhibits apoptosis of Spodopteran cells elucidating one functional aspect of PDVvankyrins. 5. That Pvank-1 and Hv1.1 do not show cooperative effect in S. littoralis when co-expressed during AcMNPV infection. Our results pave the way to developing novel means for pest control, including baculoviruses, that rely upon suppressing host immune systems by strategically weakening insect defenses to improve pathogen (i.e. biocontrol agent) infection and virulence. Also, we expect that the above result will help to develop systems for enhanced insect control that may ultimately help to reduce transmission of insect vectored diseases of humans, animals and plants as well as provide mechanisms for suppression of insect populations that damage crop plants by direct feeding.
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Farmer, Roger E. A., and Konstantin Platonov. Animal Spirits in a Monetary Model. Cambridge, MA: National Bureau of Economic Research, March 2016. http://dx.doi.org/10.3386/w22136.
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Mellies, Jay L. C. elegans as a Model for EPEC Infection. Fort Belvoir, VA: Defense Technical Information Center, November 2005. http://dx.doi.org/10.21236/ada441203.
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Cabrera, Anahi Maldonado, Blayra Maldonado Cabrera, Dalia Isabel Sánchez Machado, and Jaime López Cervantes. Wound healing therapeutic effect of chitosan nanofibers: a systematic review and meta- analysis of animal studies. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, October 2022. http://dx.doi.org/10.37766/inplasy2022.10.0121.
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Review question / Objective: Review question: Does chitosan base nanofibers has significant wound healing therapeutics effects in animal models? A preclinical systematic review of intervention will be carried out to evaluate the therapeutic effects of chitosan nanofibers on animal skin lesions. The PICO (Population, Intervention, Comparator, Outcome) scheme will be used: Intervention: full-thickness skin lesions, and the application of chitosan nanofibers as treatment for animal skin lesions. Regardless of the concentration of chitosan or other added compounds used. Comparison: No intervention, topical placebo agents and standard skin lesions treatments will be included. Outcome: wound healing area, wound closure, type of wound closure (first, second or third intention), healing time, infectious processes (antibacterial/antifungal properties), blood loss (hemostatic properties) and adverse effects.
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Li, Jiliang. Healing of Stress Fracture in an Animal Model. Fort Belvoir, VA: Defense Technical Information Center, September 2004. http://dx.doi.org/10.21236/ada433113.
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