title: Evaluation of cellular determinants required for in vitro xenotropic murine leukemia virus-related virus entry into human prostate cancer and noncancerous cells.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.
authors.forename: Sushma
authors.initials: S
authors.lastname: Bhosle
authors.forename: Suganthi
authors.initials: S
authors.lastname: Suppiah
authors.forename: Ross
authors.initials: R
authors.lastname: Molinaro
authors.forename: Yuying
authors.initials: Y
authors.lastname: Liang
authors.forename: Rebecca
authors.initials: R
authors.lastname: Arnold
authors.forename: William
authors.initials: W
authors.lastname: Diehl
authors.forename: Natalia
authors.initials: N
authors.lastname: Makarova
authors.forename: Jerry
authors.initials: J
authors.lastname: Blackwell
authors.forename: John
authors.initials: J
authors.lastname: Petros
authors.forename: Dennis
authors.initials: D
authors.lastname: Liotta
authors.forename: Eric
authors.initials: E
authors.lastname: Hunter
authors.forename: Hinh
authors.initials: H
authors.lastname: Ly
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000821:virology; D005347:Fibroblasts / Q000821:virology; D017988:Gammaretrovirus / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D009052:Leukemia Virus, Murine; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000821:virology; D011467:Prostate / Q000821:virology*; D011471:Prostatic Neoplasms / Q000821:virology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D056189:Viral Tropism; D053586:Virus Internalization; D000089842:Xenotropic and Polytropic Retrovirus Receptor
chemical_list: D043562:Receptors, G-Protein-Coupled; D011991:Receptors, Virus; C000715267:XPR1 protein, human; D000089842:Xenotropic and Polytropic Retrovirus Receptor; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease
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