Friday, March 4, 2011

XMRV replicates in primary hematopoietic cells

by XMRV Global Action on Thursday, March 3, 2011:

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:

Abstract link:

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.

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