Receptors for polytropic and xenotropic mouse leukaemia viruses encoded by a single gene at Rmc1

Yang, Yun-Liang; Guo, Lei; Xu, Shuang; Holland, Christie A.; Kitamura, Toshio; Hunter, Kent W.; Cunningham, James M.

doi:10.1038/6005

Cited by 120 publications

(119 citation statements)

References 26 publications

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“…The Xpr1 receptor has been characterized as a transmembrane protein of unknown function, although it shows some homology to yeast genes involved in signal transduction and phosphate transport (2,40,48). Previous studies have implicated Xpr1 extracellular loop sequences (ECL3 and ECL4) in mediating entry of the XMLVs.…”

Section: Discussionmentioning

confidence: 99%

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

Bhosle¹,

Suppiah²,

Molinaro³

et al. 2010

J Virol

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Prostate cancer is the most common male malignancy in Western countries and the second most common cause of cancer-related deaths in males worldwide (15,24). The known risk factors for prostate cancer are hormones (i.e., androgens), diet, sex, and race, as well as environmental and genetic factors (27). A recent study suggests that susceptibility to prostate cancer can be influenced by the genetic variations associated with an antagonistic coevolution, which occurs between a specific host locus (RNASEL), known to be involved in antiviral innate immune defense, and a viral pathogen (38). Indeed, several epidemiologic studies have supported the involvement of the RNASEL gene in the prostate cancer etiology (4,5,30,31), whereas other studies do not (9,22,34,43). Some studies have reported that individuals with a single mutated copy of the RNASEL gene have a 50% increased risk for prostate cancer, whereas those with homozygous mutant RNASEL alleles have a 2-fold-increased risk of prostate cancer (5).The RNASEL gene encodes for the RNase L protein, a constitutively expressed latent endoribonuclease, which mediates the interferon-inducible 2-5A system against viral and/or cellular double-stranded RNAs (8,16,20,23,49,50). The RNase L "Q" variant allele (R462Q) shows a 3-fold decrease in catalytic activity compared to the wild-type enzyme (5, 44). The possible association of mutant RNASEL alleles with human prostate cancers suggests an enhanced susceptibility of prostate tissues to a viral agent. This hypothesis has led to the recent identification of a new human retrovirus, xenotropic murine leukemia virus (MuLV)-related virus (XMRV), in 40% of prostate cancer patients with the QQ variant alleles of RNASEL compared to 1.5% among heterozygous (RQ) and wild-type (RR) RNASEL carriers (41). XMRV virus infection appears to be susceptible to inhibition by interferon and its downstream effector RNase L protein (7). However, a recent study has provided some evidence to show that XMRV infection is independent of the RNASEL genotype (34), suggesting that population differences and/or other environmental or genetic factors may influence the impact of RNASEL on prostate cancer development.The XMRV genome is 8,185 nucleotides in length and shares up to 95% overall nucleotide sequence identity with known xenotropic MuLVs (41). One receptor for xenotropic MuLVs is Xpr1, a 696-amino-acid protein with multiple transmembrane-spanning domains (2). Expression of this protein in Chinese hamster ovary (CHO) cells that are not known to express Xpr1 endogenously confers an enhanced susceptibility of these cells to xenotropic MuLV infection (2). Infection of hamster and mouse cells with XMRV-like virus that is derived from a prostate cancer cell line (22Rv1) also requires Xpr1 as a receptor (18). Earlier studies have demonstrated the importance of certain residues located within the putative third and fourth extracellular loops (ECL3 and ECL4) of Mus dunni's Xpr1 in conferring infection by xenotropic MuLVs (25). Furthermore, it has been shown ...

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Section: Discussionmentioning

confidence: 99%

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

Bhosle¹,

Suppiah²,

Molinaro³

et al. 2010

J Virol

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“…These results prompted us to initiate positional cloning efforts to identify the genes encoding the three retrovirus receptors, but in the meantime we and others successfully isolated human cDNAs encoding the RD114 receptor (RDR) (7,16), the xenotropic MuLV receptor (XPR1) (9,17,18), and the FeLV-C receptor (FLVCR) (15,19) by expression cloning using retroviral cDNA expression libraries. We designed PCR primers to detect the receptor genes in DNA from the radiation hybrids to determine whether the genotypic mapping would give the same results as did the phenotypic mapping.…”

Section: Resultsmentioning

confidence: 99%

Precise gene localization by phenotypic assay of radiation hybrid cells

Rasko¹,

Battini²,

Kruglyak³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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A high resolution map of the human genome previously has been constructed by using the G3 panel of human͞hamster radiation hybrid cell lines and >15,000 unique human genetic markers. By determining whether human DNA sequences are present or absent in each of the hybrids, localization of single genes may routinely be achieved at Ϸ250-kb resolution. In this paper we have tested whether similarly precise localization might be achieved by phenotypic screening of the hybrids to facilitate positional cloning of unknown genes. We assayed the susceptibility of each of the hybrid cell lines to transduction by retroviral vectors bearing different retroviral envelope proteins that recognize receptors present on human but not on hamster cells. The results for each of the retroviral vectors were informative and allowed precise localization of the receptor genes for the RD114 cat endogenous retrovirus, xenotropic murine leukemia virus, and type C feline leukemia virus. After cloning of the receptors for these retroviruses, we found that standard genotypic mapping by PCR gave results that were nearly identical to those from phenotypic mapping. These experiments show that precise gene localization by phenotypic assay of radiation hybrids is practical and was not appreciably impacted by the known instability of such hybrid cells. This technique should be applicable to many other human genes having discernible phenotypes in hamster cells and, with completion of the human genome project, will allow rapid identification of unknown genes on the basis of phenotype.T he Stanford Human Genome Center (SHGC) G3 panel of radiation hybrid cell lines consists of 83 clones of hamster cells that contain multiple independent fragments of human DNA. The panel was generated by fusing irradiated human cells with thymidine kinase-negative hamster cells and selecting clones that express human thymidine kinase (1). At the radiation dose used (10,000 rad), the human DNA is broken into fragments with an average size of 4 megabases (Mb), and each hybrid contains Ϸ18% of the human genome. By using PCR to screen these hybrids for the presence or absence of Ͼ15,000 unique human DNA markers, a high-resolution map of the human genome has been developed. DNA from these hybrids now can be screened for the presence of any new unique sequence and the results can be submitted to a web-based server to determine the precise location of the DNA sequence within Ϸ250 kb (http:͞͞ www-shgc.stanford.edu).It also is possible to screen radiation hybrid cell lines for gene expression and thereby to map genes by phenotype. For example, in 1975, Goss and Harris (2) were the first to use radiation hybrids to determine linkage of four phenotypic markers scattered on the human X chromosome. However, although there is a long history of the use of human͞hamster hybrid cell lines to localize and establish linkage maps for human genes based on phenotypic assay, this technique has not been applied to the high-resolution radiation hybrid panels that are now available. Previous stud...

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“…In fact, we and others have identified a variety of novel genes through functional assays by using retrovirus-mediated expression cloning (4)(5)(6)(7). We also applied the screening method to identify constitutive active forms of a cytokine receptor, MPL (8), and a transcription factor, STAT5 (9,10), in combination with PCR-driven random mutagenesis.…”

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confidence: 99%

A method to identify cDNAs based on localization of green fluorescent protein fusion products

Misawa

Nosaka

Morita

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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We previously established a high-efficiency, retrovirus-mediated expression cloning method. Using this system, we now have developed an expression cloning method (FL-REX; fluorescence localization-based retrovirus-mediated expression cloning) in which cDNAs can be isolated based on the subcellular localization of their protein products. Complementary DNAs generated from mRNA using random hexamers were fused to the cDNA of green fluorescent protein (GFP) in the pMX retrovirus vector. The resulting cDNA-GFP fusion library was transfected into retrovirus-packaging cells, and the derived retroviruses were used to infect NIH 3T3 cells. Infected cells then were screened to identify cDNAs of interest through the subcellular localization of the GFP-fusion products. Using FL-REX, we have identified 25 cDNAs, most of which showed reasonable subcellular localization as GFP-fusion proteins, indicating that FL-REX is useful for identification of proteins that show specific intracellular localization.

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Receptors for polytropic and xenotropic mouse leukaemia viruses encoded by a single gene at Rmc1

Cited by 120 publications

References 26 publications

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

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

Precise gene localization by phenotypic assay of radiation hybrid cells

A method to identify cDNAs based on localization of green fluorescent protein fusion products

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