Secrets of Novel Retrovirus Unfolding

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CROI: Secrets of Novel Retrovirus Unfolding

By Crystal Phend, Senior Staff Writer, MedPage Today
Published: February 21, 2010

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.