XMRV -Determination Host Range & Cellular Tropism

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XMRV

GLOBAL ACTION

CROI XMRV presenters Devadas et al @ FDA

continuing to look @ XMRV pathogenesis

By XMRV Global Action

Thursday 3 March 2011

FDA

The following is from the Devadas et al CROI poster

entitled:

*Determination of Host Range

and Cellular Tropism of XMRV*.

Refreshing, in the stated thirst by the researchers to

learn more about XMRV pathogenesis and modes of

transmission.

A nice counterbalance too, to the select CROI

researchers saying in effect,

*don't bother researching

ME/CFS/XMRV connections*.

Poster link:

http://www.retroconference.org/2011/PDFs/235.pdf

Abstract link:

http://www.retroconference.org/2011/Abstracts/41766.htm

Paper # 235

Determination of Host Range

and Cellular Tropism of XMRV

Krishnakumar Devadas*, MK Haleyur Giri Setty, R

Viswanath, O Wood, S Tang, J Zhao, A Dastyar, X

Wang, S Lee, and I Hewlett

Ctr for Business and Economic Res, FDA, Rockville,

MD, US

The findings and conclusions in this abstract have

not been formally disseminated by the Food and

Drug Administration and should not be construed to

represent any Agency determination or policy.

Background:

Xenotropic murine leukemia virus-related virus

(XMRV) is a newly identified retrovirus identified in

familial cases of prostate cancer tissue using a virus

gene array.

Although initial reports have identified XMRV

predominantly in the prostate, recent reports of

detection of XMRV in blood cells of patients with

chronic fatigue syndrome suggests that blood cells

could act as a primary target and reservoir for XMRV

and help in disseminating infection throughout the

body.

The aim of this study is to elucidate possible routes

of transmission and to determine the host range and

cellular tropism of XMRV, particularly in cells derived

from the hematopoietic system.

Methods:

To determine the host range and tropism of XMRV,

culture supernatants containing infectious virus from

22RV-1 or DU145-clone-7 cells were used to infect

human cell lines Jurkat, H9, HL60, U937, DU145,

LNCaP, and primary monocytes and monocyte-derived

macrophages (MDM).

Infected cells were monitored for XMRV replication

over a period of 5 days.

XMRV replication was quantitated by RT-PCR, DNA

PCR, and Western blotting.

To determine the tropism of XMRV, GHOST(3) cells

expressing CD4 and other co-receptors like CXCR4,

CCR5, and BONZO, were infected with XMRV and

viral replication quantitated by real-time PCR.

Results:

Replication of XMRV could be observed in the

prostate cancer cell lines DU145 and LNCaP, T cell

lines Jurkat and H9, B cell line HL60, and in primary

monocytes and MDM.

The levels of XMRV transcripts were lower in primary

monocytes compared to T cell lines suggesting less

efficient replication in these cells.

GHOST(3) cells expressing CD4 could support viral

replication.

However, more viral replication was detected in

GHOST(3) cells expressing other co-receptors

together with CD4.

Conclusions:

Viral replication could be identified in primary

hematopoietic cells and cell lines investigated.

In addition, viral replication was considerably lower

in primary monocytes, suggesting less efficient

replication in these cells.

Studies with GHOST(3) cells indicate that CD4 and

other co-receptors may act in a synergistic manner to

enhance XMRV infection.

These observations will help to further our

understanding of XMRV pathogenesis and provide

insights into the modes of transmission involved in

XMRV infection.