title: Rmcf2, a xenotropic provirus in the Asian mouse species Mus castaneus, blocks infection by polytropic mouse gammaretroviruses.
abstract: Cells from the Asian wild mouse species Mus castaneus are resistant to infection by the polytropic host range group of mouse gammaretroviruses. Two factors are responsible for this resistance: a defective XPR1 cell surface receptor for polytropic murine leukemia viruses (P-MLVs), and a resistance factor detectable only in interspecies hybrids between M. castaneus and mice with an XPR1 variant that permits infection by xenotropic MLVs (X-MLVs) as well as P-MLVs. This second novel virus resistance phenotype has been associated with expression of viral Env glycoprotein; Northern blotting with specific hybridization probes identified a spliced X-MLV env message unique to virus-resistant mice. These observations suggest that resistance is due to expression of one or more endogenous X-MLV envelope genes that interfere with infection by exogenous P-MLVs. M. castaneus contains multiple X-MLV proviruses, but serial backcrosses reduced this proviral content and permitted identification of a single proviral env sequence inherited with resistance. The resistance phenotype and the provirus were mapped to the same site on distal chromosome 18. The provirus was shown to be a full-length provirus highly homologous to previously described X-MLVs. Use of viral pseudotypes confirmed that this resistance gene, termed Rmcf2, prevents entry of P-MLVs. Rmcf2 resembles the virus resistance genes Fv4 and Rmcf in that it produces Env glycoprotein but fails to produce infectious virus; the proviruses associated with all three resistance genes have fatal defects. This type of provirus Env-mediated resistance represents an important defense mechanism in wild mouse populations exposed to endemic infections.
authors: Laboratory of Molecular Microbiology, National Institute and Allergy and Infectious Diseases, Bethesda, MD 20892-0460, USA.
authors: Tiyun
authors: T
authors: Wu
authors: Yuhe
authors: Y
authors: Yan
authors: Christine A
authors: CA
authors: Kozak
mesh_terms: D000483:Alleles; D000818:Animals; D002875:Chromosomes / Q000235:genetics; D003433:Crosses, Genetic; D004198:Disease Susceptibility; D005814:Genes, Viral / Q000235:genetics / Q000502:physiology*; D016678:Genome; D009052:Leukemia Virus, Murine / Q000235:genetics*; D007942:Leukemia, Experimental / Q000235:genetics / Q000821:virology*; D051379:Mice; D008969:Molecular Sequence Data; D009115:Muridae; D011533:Proviruses / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled; D011991:Receptors, Virus / Q000235:genetics; D012192:Retroviridae Infections / Q000235:genetics / Q000821:virology*; D014412:Tumor Virus Infections / Q000235:genetics / Q000821:virology*; D000089842:Xenotropic and Polytropic Retrovirus Receptor
chemical_list: D043562:Receptors, G-Protein-Coupled; D011991:Receptors, Virus; D000089842:Xenotropic and Polytropic Retrovirus Receptor; C000715268:Xpr1 protein, mouse