Date Published: July 24, 2011
Publisher: Hindawi Publishing Corporation
Author(s): Prachi Sharma, Kenneth A. Rogers, Suganthi Suppiah, Ross J. Molinaro, Nattawat Onlamoon, John Hackett, Gerald Schochetman, Eric A. Klein, Robert H. Silverman, François Villinger.
Although XMRV dissemination in humans is a matter of debate, the prostate of select patients seem to harbor XMRV, which raises questions about its potential route of transmission. We established a model of infection in rhesus macaques inoculated with XMRV. In spite of the intravenous inoculation, all infected macaques exhibited readily detectable XMRV signal in the reproductive tract of all 4 males and 1 female during both acute and chronic infection stages. XMRV showed explosive growth in the acini of prostate during acute but not chronic infection. In seminal vesicles, epididymis, and testes, XMRV protein production was detected throughout infection in interstitial or epithelial cells. In the female monkey, epithelial cells in the cervix and vagina were also positive for XMRV gag. The ready detection of XMRV in the reproductive tract of male and female macaques infected intravenously suggests the potential for sexual transmission for XMRV.
Xenotropic murine leukemia virus-related retrovirus (XMRV), a gammaretrovirus, was initially discovered in a study that used prostate carcinoma tissues and later in a study that used blood of chronic fatigue syndrome patients [1, 2], although other labs have been unable to detect XMRV in such patients  or have suggested that most of the findings based on nucleic amplification techniques were secondary to contamination with mouse DNA [4–7]. Moreover the link to chronic fatigue has recently been seriously questioned . However, the detection of XMRV in select prostate cancers was not all based on methods using nucleic acid amplification, and while the etiological role of XMRV infection for cancer remains uncertain, XMRV represents a novel gamma retrovirus capable of infecting several human host cell lines , and hence, a potential zoonotic agent. In fact, infection of humans with this virus might have resulted from a zoonotic transmission from mouse to man  similar to the transspecies transmission reported with the Koala retrovirus, a gammaretrovirus closely related to XMRV . Though both cell-associated and cell-free transmission of XMRV have been reported  and there is indirect evidence for potential respiratory  or sexual  transmission, the exact route or mechanism of transmission still remains unresolved. To better understand the XMRV pathogenesis, our lab recently established an animal model of XMRV infection using rhesus macaques. Results of this study have recently been published, demonstrating unequivocally that XMRV is infectious for primates, inducing a persistent infection which, given the right context, may be reactivated in vivo . During the histological analyses of these animals, it was realized that in spite of the generalized infection, XMRV appeared to show a predilection for tissues and organs of the reproductive tract in this model, suggesting the potential for sexual transmission.
A detailed analysis of the XMRV infection, viral dissemination, and antibody responses in these macaques is published elsewhere . Here, our analyses focused on the viral distribution in the reproductive tract and its potential implication for sexual transmission. Briefly, none of the infected animals showed any obvious clinical symptoms for the entire 9 months of followup, based on activity levels, food intake, hematological, or serum chemistry findings. The infected animals were sacrificed at different times after infection to obtain tissues representative of the acute and chronic virus dissemination with clear separation from one another. Control and XMRV-infected tissues were, however, embedded and sectioned in parallel, and assayed together as batches. All tissues were Lymphoid organs like spleen, lymph nodes, and the gastrointestinal lamina propria and nonlymphoid organs like lung, brain, liver, and bone marrow contained cells positive for XMRV by IHC and/or FISH for which semiquantitative analysis was performed . Of note, several tissues such as CNS, heart, adrenal gland, gall bladder, kidney, and urinary bladder were negative by IHC with only a rare single FISH signal . In contrast, there was an absence of signal all organs of uninfected control rhesus macaques run in the same batches as samples from XMRV infected monkeys.
Eric A. Klien, John Hackett, Robert H. Silverman, and François Villinger designed the study. Prachi Sharma, Suganthi Suppiah, Ross J. Molinaro, Nattawat Onlamoon, Kenneth A. Rogers, and François Villinger performed the research and analyzed the data. Prachi Sharma wrote the paper.