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- 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. 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 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.

``````

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