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Evaluation of cellular determinants required for XMRV entry

Discussion in 'XMRV Research and Replication Studies' started by natasa778, Apr 24, 2010.

  1. natasa778

    natasa778 Senior Member

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    J Virol. 2010 Apr 21. [Epub ahead of print]

    Evaluation of cellular determinants required for in vitro XMRV entry of human prostate cancer and non-cancerous cells.

    Bhosle S, Suppiah S, Molinaro R, Liang Y, Arnold R, Diehl W, Makarova N, Blackwell J, Petros J, Liotta D, Hunter E, Ly H.

    Departments of Pathology and Laboratory Medicine, Urology, Medicine, and Chemistry, Emory Vaccine Center, Emory University, Atlanta, GA 30322; The Atlanta VA Medical Center, Decatur, GA 30033.
    Abstract

    The newly identified retrovirus - the xenotropic MuLV-related virus XMRV - has recently been shown to be strongly associated with familial prostate cancer in humans (41). While that study showed evidence of XMRV infection exclusively in the prostatic stromal fibroblasts, a recent study found XMRV protein antigens mainly in malignant prostate epithelial cells (34). To help understand the mechanisms behind XMRV infection, we show that prostatic fibroblast cells express Xpr1, a known receptor of XMRV, but its expression is absent in other cell lines of the prostate (i.e., epithelial and stromal smooth muscle cells). We also show that certain amino acid residues located within the predicted extracellular loop (ECL3 and ECL4) sequences of Xpr1 are required for efficient XMRV entry. While we found strong evidence to support XMRV infection of prostatic fibroblast cell lines via Xpr1, we learned that XMRV was indeed capable of infecting cells that did not necessarily express Xpr1, such as those of the prostatic epithelial and smooth muscle origins. Further studies suggest that the expression of Xpr1 and certain genotypes of the RNASEL gene, which could restrict XMRV infection, may play important roles in defining XMRV tropisms in certain cell types. Collectively, our data reveal important cellular determinants required for XMRV entry into different human prostate cells in vitro, which may provide important insights into the possible role of XMRV as an etiologic agent in human prostate cancer.

    PMID: 20410264
     
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