CROI: Secrets of Novel Retrovirus Unfolding
By Crystal Phend, Senior Staff Writer, MedPage Today
Published: February 21, 2010
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SAN FRANCISCO - The mystery surrounding a retrovirus recently implicated in prostate cancer and possibly chronic fatigue syndrome is beginning to yield clues.
The virus, known as XMRV, has been confirmed to replicate primarily in reproductive organs and lymphoid tissue, according to a primate study reported at the Conference on Retroviruses and Opportunistic Infections.
A second study found markers that could be the key to developing an assay for the large scale epidemiologic studies needed to determine how widely the virus has penetrated in the population, and what effect it has.
"We're at a very, very early stage working with this virus," said conference vice-chair John Coffin, PhD, of Tufts University in Boston.Action Points
Note that these studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
He likened it to the early days of HIV research, when scientists scrambled to make sense of the virus, but cautioned that has yet to be any clear evidence linking it to disease.
XMRV burst onto the scene four years ago when researchers doing a broad sweep for viruses in prostate cancer samples turned up evidence of a retrovirus that resembled the murine leukemia virus, earning it the abbreviation xenotropic murine leukemia-related virus (XMRV).
"The similarity [in genetic sequence] is so striking that although we don't know the details we have to assume it's coming from mice," Stephen Goff, PhD, of Columbia University in New York City, told MedPage Today.
The genetic sequence of all XMRV isolates tested across the country, and across diseases, show so little divergence that the virus must have only recently jumped to humans -- likely from a point source and with limited numbers of replication cycles during transmission, Goff said in a plenary lecture on XMRV at the conference.
This implies that a vaccine might be much easier to develop than for HIV, he explained at a press conference.
However, while this class of retroviruses appears to be characterized by lifelong infection that cannot be cleared by the immune system, there's no clear proof yet that XMRV causes illness or the diseases it's been linked to, he emphasized.
Even the links to prostate cancer and chronic fatigue syndrome are controversial, with centers reporting anywhere from 0% to 23% and 0% to 67% prevalence in tested cases, respectively, Goff noted.
To learn more about how the virus might interact with the human immune system, scientists at the Cleveland Clinic, Yerkes National Primate Research Center at Emory University, and Abbott Diagnostics collaborated on an animal model.
Prachi Sharma, PhD, of Emory, presented part of the results involving monkeys.
She reported that acutely infected monkeys tested positive for virus replicating in a number of tissues.
Chronic infection, though, appeared largely limited to CD4+ T cells in lymphoid organs -- spleen, lymph nodes, and GI tract -- as well as in reproductive organs, including prostate, testes, ovaries, vagina, and cervix.
Other experimental lab studies have shown the virus to be androgen and hormone responsive, which bears on the cell types in which it will be found, Goff said.
It was notable that the monkeys exhibited no visible symptoms or fever when infected, said John Hackett, Jr., PhD, of Abbott Diagnostics in Abbott Park, Ill.
He reported the group's efforts to develop assays to detect XMRV infections.
In the monkeys, antibodies to gag p30, env gp70 and env p15E were observed.
The researchers were also able to show, for the first time, the existence of antibodies to multiple XMRV proteins in humans.
However, they occured in only three of 2,851 human blood samples.
Detection in humans has proven challenging, but whether this reflects the virus' life cycle, a combination of viral properties and the length of time between infection and disease, or some other factor is unclear, Hackett said.
"Part of it is the ability to identify it to begin with," Hackett told MedPage Today. "You could argue we haven't been looking for it."
Sharma's study was supported by Abbott Diagnostics and a grant from the National Institutes of Health.
Hackett reported conflicts of interest with Abbott Diagnostics.
Goff reported support from the Howard Hughes Medical Institute and the Department of Defense Prostate Program.
Primary source: Conference on Retroviruses and Opportunistic Infections
Source reference:
Goff S "Mouse to Man? XMRV and Human Disease" CROI 2010; Abstract 132.
Additional source: Conference on Retroviruses and Opportunistic Infections
Source reference:
Qui X, et al "XMRV: Examination of Viral Kinetics, Tissue Tropism, and Serological Markers of Infection" CROI 2010; Abstract 151.
Additional source: Conference on Retroviruses and Opportunistic Infections
Source reference:
Sharma P, et al "Organ and Cell Lineage Dissemination of XMRV in Rhesus Macaques during Acute and Chronic Infection" CROI 2010; Abstract 150 LB.
I <3 Coffin. And not just because he uses the phrase "grind the sausage"! 
