XMRV and Macaque Monkeys

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http://bit.ly/fKUVxf


CFIDS Watch




Thursday, January 6, 2011




Macaque monkeys and XMRV



Possibly the most significant CFS-related research
since the Whittemore-Peterson Institute's XMRV
study was published last year by a group connected
with Emory University, Abbot Labs, and the
Cleveland Clinic.

In this study, rhesus macaque monkeys were
injected with XMRV, and then their blood and organs
were tested to track the progression of the infection.


After a few weeks, XMRV was almost totally gone
from the blood. But the infection had spread to many
of the organs, including the lungs, spleen, liver,
lymphatic system, bronchial passages, gut, and the
sex organs.


When the monkeys were later injected with a bolus
of foreign peptides (which mimics an acute
infection, an immunization, or an acute mold
exposure) there was a huge reactivation of infectious
XMRV.


Stress and certain hormones also appear to be
significant reactivators.


This study is totally consistent with my observations
of the progression of my own illness over the past 16
years.

It also sheds new light on several recent studies
which failed to find XMRV in the blood of patients
with XRMV.


I believe it should provide new impetus and direction
for future XMRV and CFS-related research.




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* XMRV: Examination of Viral Kinetics, Tissue
Tropism, and Serological Markers of Infection -
The study abstract. [~jvr: see below:
http://bit.ly/eoIxX9]


* XMRV Infection in Primates - Dr. Paul Cheney's
detailed discussion of the study http://bit.ly/f3XhyR


* Monkey Business - Political cartoons commenting
on the study: http://bit.ly/hx1Y9Y


* More Monkeys - More politics: http://bit.ly/i03IaT




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http://bit.ly/eoIxX9


17th Conference on Retroviruses
and Oppertunic Infection



Session 41-Oral Abstracts
Virus–Host Interaction: HIV and XMRV
Friday, 9:30 am-12 noon; Room 2011



Paper # 151


XMRV: Examination of Viral Kinetics, Tissue
Tropism, and Serological Markers of Infection

X Qiu1, P Swanson1, K-C Luk1, J Das Gupta2, N
Onlamoon3, R Silverman2, F Villinger3, S Devare1, G
Schochetman1, and John Hackett, Jr*1

1Abbott Diagnostics, Abbott Park, IL, US; 2Cleveland
Clin, OH, US; and 3Yerkes Natl Primate Res Ctr,
Emory Univ, Atlanta, GA, US



Background:

Xenotropic Murine Leukemia Virus-related Retrovirus
(XMRV) is a human retrovirus recently discovered in
familial prostate cancer tissue using DNA array based
Virochip technology.

Understanding viral replication kinetics, tissue
tropism, and the host immune response is
fundamental to establish the etiology of XMRV
infection in human disease.

Development of serologic assays to detect
XMRV-specific antibodies would facilitate
epidemiologic studies.



Methods:

Five rhesus macaques were inoculated intravenously
with XMRV.

Blood was collected throughout the course of
infection, and tissue from multiple organs was
harvested at necropsy.

Two macaques were necropsied at day 6 or 7 and
one at day 144 post infection.

The remaining 2 animals were re-inoculated with
XMRV on day 158 and necropsied on day 291.

XMRV-specific immunoreactivity was monitored by
Western blot using viral lysate.

Recombinant env gp70, p15E and gag p30 were
utilized to develop serologic assays on the
high-throughput automated ARCHITECT instrument
system (Abbott Diagnostics).




Results:

XMRV inoculation resulted in low transient plasma
viremia, although proviral DNA persisted in
circulating peripheral blood mononuclear cells for
several weeks.

Of interest, the earliest leukocyte targets were CD4+
T cells and NK cells followed by CD8+ enriched T and
CD20+ enriched B cells (50% positive); CD14+
monocytes were negative.

Animals sacrificed at the acute stage showed
evidence of viral replication in spleen, lung, lymph
nodes and liver.

In contrast, sacrifice of 2 animals at 19 weeks post
XMRV re-inoculation showed greater dissemination of
XMRV DNA and RNA in various organs including the
GI and urinary tract as well as in vaginal tissue of
the one female.

By Western blot analysis, all 3 chronically infected
macaques developed antibody responses to env and
gag proteins.

The serologic assays demonstrated 100% sensitivity
by detecting all Western blot positive serial bleeds
from the XMRV-infected macaques.

Preliminary results showed evidence of detectable
reactivity to all 3 antigens in a low proportion
(~0.1%) of US blood donors.



Conclusions:

These data suggest that lymphocytes are a primary
target for replication persistence (low grade
replication) of XMRV in the absence of detectable
plasma viremia.

This study identified specific serological markers
useful for detection of antibodies induced by XMRV
infection. The prototype antibody assays will
facilitate large-scale epidemiological studies.






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The 17th Conference on Retroviruses
and Oppertunic Infection

Session 41-Oral Abstracts
Virus–Host Interaction: HIV and XMRV
Friday, 9:30 am-12 noon; Room 2011

can be found at: http://bit.ly/ijzyPo








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