PMID- 21325416 OWN - NLM STAT- MEDLINE DCOM- 20110614 LR - 20211020 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 85 IP - 9 DP - 2011 May TI - Infection, viral dissemination, and antibody responses of rhesus macaques exposed to the human gammaretrovirus XMRV. PG - 4547-57 LID - 10.1128/JVI.02411-10 [doi] AB - 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. FAU - Onlamoon, Nattawat AU - Onlamoon N AD - Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA. FAU - Das Gupta, Jaydip AU - Das Gupta J FAU - Sharma, Prachi AU - Sharma P FAU - Rogers, Kenneth AU - Rogers K FAU - Suppiah, Suganthi AU - Suppiah S FAU - Rhea, Jeanne AU - Rhea J FAU - Molinaro, Ross J AU - Molinaro RJ FAU - Gaughan, Christina AU - Gaughan C FAU - Dong, Beihua AU - Dong B FAU - Klein, Eric A AU - Klein EA FAU - Qiu, Xiaoxing AU - Qiu X FAU - Devare, Sushil AU - Devare S FAU - Schochetman, Gerald AU - Schochetman G FAU - Hackett, John Jr AU - Hackett J Jr FAU - Silverman, Robert H AU - Silverman RH FAU - Villinger, Francois AU - Villinger F LA - eng GR - P51 RR000165/RR/NCRR NIH HHS/United States GR - R01 CA103943/CA/NCI NIH HHS/United States GR - CA103943/CA/NCI NIH HHS/United States GR - DRR000165/PHS HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20110216 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Antibodies, Viral) SB - IM MH - Animals MH - Antibodies, Viral/*blood MH - CD4-Positive T-Lymphocytes/virology MH - Chronic Disease MH - *Disease Models, Animal MH - Epithelial Cells/virology MH - Humans MH - Lymphocytes/virology MH - Macaca mulatta/*virology MH - Macrophages/virology MH - Male MH - Primate Diseases/immunology/pathology/*virology MH - Proviruses/isolation & purification MH - Retroviridae Infections/immunology/pathology/*virology MH - Viral Tropism MH - Viremia MH - Virus Activation MH - Virus Latency MH - Xenotropic murine leukemia virus-related virus/*immunology/*pathogenicity PMC - PMC3126245 EDAT- 2011/02/18 06:00 MHDA- 2011/06/15 06:00 PMCR- 2011/11/01 CRDT- 2011/02/18 06:00 PHST- 2011/02/18 06:00 [entrez] PHST- 2011/02/18 06:00 [pubmed] PHST- 2011/06/15 06:00 [medline] PHST- 2011/11/01 00:00 [pmc-release] AID - JVI.02411-10 [pii] AID - 2411-10 [pii] AID - 10.1128/JVI.02411-10 [doi] PST - ppublish SO - J Virol. 2011 May;85(9):4547-57. doi: 10.1128/JVI.02411-10. Epub 2011 Feb 16.