Infection, Viral Dissemination, and Antibody Responses of Rhesus Macaques Exposed to the Human Gammaretrovirus XMRV
| Autor: | Prachi Sharma, Eric A. Klein, Jeanne M. Rhea, Jaydip Das Gupta, Christina Gaughan, John R. Hackett, Gerald Schochetman, Sushil G. Devare, Francois Villinger, Nattawat Onlamoon, Robert H. Silverman, Ross J. Molinaro, Beihua Dong, Kenneth A. Rogers, Suganthi Suppiah, Xiaoxing Qiu |
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| Rok vydání: | 2011 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male Xenotropic murine leukemia virus-related virus Immunology Viremia Biology Antibodies Viral urologic and male genital diseases Microbiology Immune system Proviruses Virology Virus latency medicine Animals Humans Lymphocytes Gammaretrovirus Macrophages Primate Diseases virus diseases Epithelial Cells biology.organism_classification medicine.disease Macaca mulatta Virus Latency Disease Models Animal Viral Tropism Chronic infection Insect Science Chronic Disease Tissue tropism biology.protein Pathogenesis and Immunity Virus Activation Antibody Retroviridae Infections |
| Zdroj: | Journal of Virology. 85:4547-4557 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.02411-10 |
| Popis: | Xenotropic murine leukemia-related virus (XMRV) was identified in association with human prostate cancer and chronic fatigue syndrome. To examine the infection potential, kinetics, and tissue distribution of XMRV in an animal model, we inoculated five macaques with XMRV intravenously. XMRV established a persistent, chronic disseminated infection, with low transient viremia and provirus in blood lymphocytes during acute infection. Although undetectable in blood after about a month, XMRV viremia was reactivated at 9 months, confirming the chronicity of the infection. Furthermore, XMRV Gag was detected in tissues throughout, with wide dissemination throughout the period of monitoring. Surprisingly, XMRV infection showed organ-specific cell tropism, infecting CD4 T cells in lymphoid organs including the gastrointestinal lamina propria, alveolar macrophages in lung, and epithelial/interstitial cells in other organs, including the reproductive tract. Of note, in spite of the intravenous inoculation, extensive XMRV replication was noted in prostate during acute but not chronic infection even though infected cells were still detectable by fluorescence in situ hybridization (FISH) in prostate at 5 and 9 months postinfection. Marked lymphocyte activation occurred immediately postinfection, but antigen-specific cellular responses were undetectable. Antibody responses were elicited and boosted upon reexposure, but titers decreased rapidly, suggesting low antigen stimulation over time. Our findings establish a nonhuman primate model to study XMRV replication/dissemination, transmission, pathogenesis, immune responses, and potential future therapies. |
| Databáze: | OpenAIRE |
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