Pletionmucosal Effects of co-factors on replication Effects of co-infection e.g.
Pletionmucosal Effects of co-factors on replication Effects of co-infection e.g. mTb on replication End organ dysfunctionNot feasible Feasible, but not performed Feasible, but not performed Not feasibleNot done Not PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26104484 done Not done Not doneNot tested Not tested Not tested Not testedNef, Env (coreceptor usage), protease Thy/Liv organ Not applicable Not determined Not determined Thy/Liv organ undergoes severe thymocyte depletionYes Yes Yes Yes Yes YesNot tested Not tested Not tested Not tested Not tested Not testedof infection to mouse lymph nodes, intestines and spleen. X4 HIV isolate was also found to be capable of mucosal transmission via both vaginal and rectal routes although the efficiency of infection was lower than R5 virus. Mucosally infected RAG-hu mice displayed CD4 T cell depletion, but depletion occurred later and was not as dramatic as seen in mice after intraperitoneal infection. Advantages of the RAG-hu model for studying HIV infection include its capacity to support chronic productive HIV infection for over 1 year, to display CD4 depletion and to being susceptible to infection by either vaginal or rectal routes. HIV infection may undermine the human immune response of RAG-hu mice. Studies using the RAG-hu mouse system by the Akkina group to model Dengue fever, for which there is currently no ideal animal model available to study viral pathogenesis and to test vaccines, may be more informative of the capacity of RAG-hu mice to generate primary human immune responses [38]. There are 4 serotypes of Dengue virus and re-infection of individuals with a second serotype virus causes worse disease than infection with the primary virus due to antibody-dependent enhancement. After challenges of RAGhu mice with Dengue virus the mice become infected and develop Dengue-specific antibody. Viremia (106 particles/ mL) lasts up to 2 weeks and Dengue viral replication is detected in the mouse spleens. Dengue-specific IgM and IgG responses are first detected at 2 weeks and at 6 weeks after infection, respectively. Dengue virus neutralization was detected in the sera of some mice at a titer of up to 1,000 by using a FACS-based assay. Of interest was the observation that the immune response to Dengue was much more robust than the immune response to HIV after infection. This may reflect HIV-associated compromise of the human immune system in the RAG-hu mice. Future studies by the Akkina group using this model will include evaluating the long-term effects of microbicides,studying viruses that infect the hematolymphoid system, evaluating gene therapy strategies using vectors carrying anti-HIV genes and drug-selection makers, investigation of the mechanism of antibody-dependent enhancement during Dengue infection and the testing of Dengue vaccines. Dr. Luban reported on the system developed by Markus Manz at his Institute, of injecting human CD34+ HSC intrahepatically into newborn Balb/c RAG2-/-c-/- mice (Table 3) [15]. These mice were obtained from Dr. Weissman, who originally got them form Dr. Mamoru Ito in Japan. Strain-specific factors contributed to the degree of reconstitution. Mice carrying the same RAG2 and c deletions on the C57BL/6 background did not become LY317615 web reconstituted with human leukocytes. In contrast, the lymphoid tissues of the Balb/c RAG2-/-c-/- mice display reconstitution with human B cells and T cells and population PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26866270 of the thymus with human T cells. No significant population of human leukocytes was detected in the mouse mucosa or.
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