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Corresponding author. Mailing address: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322. Phone: (404) 712-2841. Fax: (404) 727-8538. E-mail: hly@emory.edu

We thank D. Miller for the pLSXN-Xpr1 plasmid; J. Olsen for R187 cells; L. Chung for Pt-C and Pt-N cells; V. Rotter for fibroblast (Pf179T), epithelial (Ep156T), and smooth muscle (Pm151T) cells; R. Silverman for DU145-C7 cells, XMRV, and its molecular clone; A. Nusrat and L. Chung for antibodies against vimentin, cytokerin, and myosin; A. Nusrat and P. Nava for siRNA and antibody against the desmoglein-2 gene; and J. Heimburg-Molinaro for critical reading of the manuscript.

We also thank the Emory Biomarker Service Center for genotyping the cell lines.

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Research Funding:

This study was supported in part by grants from the American Cancer Society (RSG-06-162-01-GMC), the pilot component of the NIH center grants to the Emory CFAR (P30 AI050409), and the Emory-Winship Cancer Institute (P30 CA138292); by a generous seed grant from D. Liotta to H.L.; and by grant NIH AI-40317 to Y.L. and T. Parslow.

Evaluation of Cellular Determinants Required for In Vitro Xenotropic Murine Leukemia Virus-Related Virus Entry into Human Prostate Cancer and Noncancerous Cells

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Journal Title:

Journal of Virology

Volume:

Volume 84, Number 13

Publisher:

, Pages 6288-6296

Type of Work:

Article | Final Publisher PDF

Abstract:

The newly identified retrovirus—the xenotropic murine leukemia virus-related virus (XMRV)—has recently been shown to be strongly associated with familial prostate cancer in humans (A. Urisman et al., PLoS Pathog. 2:e25, 2006). 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 (R. Schlaberg et al., Proc. Natl. Acad. Sci. U. S. A. 106:16351-16356, 2009). To help elucidate 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. Although 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.

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© 2010, American Society for Microbiology

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