title: Infection, viral dissemination, and antibody responses of rhesus macaques exposed to the human gammaretrovirus XMRV.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Nattawat
authors.initials: N
authors.lastname: Onlamoon
authors.forename: Jaydip
authors.initials: J
authors.lastname: Das Gupta
authors.forename: Prachi
authors.initials: P
authors.lastname: Sharma
authors.forename: Kenneth
authors.initials: K
authors.lastname: Rogers
authors.forename: Suganthi
authors.initials: S
authors.lastname: Suppiah
authors.forename: Jeanne
authors.initials: J
authors.lastname: Rhea
authors.forename: Ross J
authors.initials: RJ
authors.lastname: Molinaro
authors.forename: Christina
authors.initials: C
authors.lastname: Gaughan
authors.forename: Beihua
authors.initials: B
authors.lastname: Dong
authors.forename: Eric A
authors.initials: EA
authors.lastname: Klein
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Qiu
authors.forename: Sushil
authors.initials: S
authors.lastname: Devare
authors.forename: Gerald
authors.initials: G
authors.lastname: Schochetman
authors.forename: John
authors.initials: J
authors.lastname: Hackett
authors.forename: Robert H
authors.initials: RH
authors.lastname: Silverman
authors.forename: François
authors.initials: F
authors.lastname: Villinger
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002908:Chronic Disease; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000821:virology; D006801:Humans; D008214:Lymphocytes / Q000821:virology; D008253:Macaca mulatta / Q000821:virology*; D008264:Macrophages / Q000821:virology; D008297:Male; D018419:Primate Diseases / Q000276:immunology / Q000473:pathology / Q000821:virology*; D011533:Proviruses / Q000302:isolation & purification; D012192:Retroviridae Infections / Q000276:immunology / Q000473:pathology / Q000821:virology*; D056189:Viral Tropism; D014766:Viremia; D014775:Virus Activation; D017735:Virus Latency; D058008:Xenotropic murine leukemia virus-related virus / Q000276:immunology* / Q000472:pathogenicity*
chemical_list: D000914:Antibodies, Viral