Infection, viral dissemination and antibody responses of Rhesus macaques exposed to the human gammaretrovirus XMRV – Source: Journal of Virology, Feb 16, 2011

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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 5 macaques with XMRV intravenously.

XMRV established a persistent chronic disseminated infection, with low transient viremia and provirus in blood lymphocytes during acute infection. [Viremia is presence of a virus in the blood. Provirus is a virus genome that is integrated into the DNA of a host cell.]

Although undetectable in blood after about a month, XMRV viremia was reactivated at 9 month confirming the chronicity [persistence] of the infection.

Furthermore, XMRV gag was detected in tissues throughout, with wide dissemination throughout the entire period of monitoring.

Surprisingly, XMRV infection showed organ specific cell tropism [types of cells the virus infects]: CD4 T cells in lymphoid organs including the gastrointestinal lamina propria [mucosal lining], 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 FISH in prostate at 5 and 9 months post infection. [FISH – fluorescence in situ hybridization – is a test that 'maps' the genetic material in a cell.]

Marked lymphocyte activation occurred immediately post infection, 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.

Source: Journal of Virology, Feb 16, 2011. By Onlamoon N, Das Gupta J, Sharma P, rogers K, Suppiah S, Rhea J, Molinaro RJ, Gaughan C, Dong B, Klein EA, Qiu X, Devare S, Schochetman g, Hackett J, Silverman RH, Villinger F. Department of Pathology and Laboratory Medicine, Emory University School of Medicine and Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia; Lerner Research Institute and Glickman Urological and Kidney Institute and LRI, Cleveland Clinic Foundation, Cleveland, Ohio; Abbott Diagnostics, Emerging Pathogens and Virus Discovery, Abbott Park, Illinois, USA.  [Email fvillin@emory.edu]

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