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Title: Infection, viral dissemination, and antibody responses of rhesus macaques exposed to the human gammaretrovirus XMRV
Authors: Nattawat Onlamoon
Jaydip Das Gupta
Prachi Sharma
Kenneth Rogers
Suganthi Suppiah
Jeanne Rhea
Ross J. Molinaro
Christina Gaughan
Beihua Dong
Eric A. Klein
Xiaoxing Qiu
Sushil Devare
Gerald Schochetman
John Hackett
Robert H. Silverman
François Villinger
Emory University School of Medicine
Cleveland Clinic Foundation
Emory University
Abbott Laboratories
Mahidol University
Keywords: Immunology and Microbiology
Issue Date: 1-May-2011
Citation: Journal of Virology. Vol.85, No.9 (2011), 4547-4557
Abstract: 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. © 2011, American Society for Microbiology.
ISSN: 10985514
Appears in Collections:Scopus 2011-2015

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