Infection, viral dissemination and antibody responses of Rhesus macaques exposed to XMRV

Infection, viral dissemination and antibody responses of Rhesus macaques exposed to the human gammaretrovirus XMRV

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 Jr., Robert H Silverman, and François Villinger*:

Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta GA; Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH; Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, GA; Glickman Urological and Kidney Institute and LRI, Cleveland Clinic Foundation, Cleveland, OH; Abbott Diagnostics, Emerging Pathogens and Virus Discovery, Abbott Park, IL
* To whom correspondence should be addressed. Email: fvillin@emory.edu.

Abstract
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.

Although undetectable in blood after about a month, XMRV viremia was reactivated at 9 month confirming the chronicity 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: 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 FISH in prostate at 5 and 9 months post infection.

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.