Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA.
J Virol. 2010 Dec;84(24):12841-9. doi: 10.1128/JVI.01863-10. Epub 2010 Oct 13.
Laboratory mouse strains carry endogenous copies of the xenotropic mouse leukemia viruses (X-MLVs), named for their inability to infect cells of the laboratory mouse. This resistance to exogenous infection is due to a nonpermissive variant of the XPR1 gammaretrovirus receptor, a resistance that also limits in vivo expression of germ line X-MLV proviruses capable of producing infectious virus. Because laboratory mice vary widely in their proviral contents and in their virus expression patterns, we screened inbred strains for sequence and functional variants of the XPR1 receptor. We also typed inbred strains and wild mouse species for an endogenous provirus, Bxv1, that is capable of producing infectious X-MLV and that also contributes to the generation of pathogenic recombinant MLVs. We identified the active Bxv1 provirus in many common inbred strains and in some Japanese Mus molossinus mice but in none of the other wild mouse species that carry X-MLVs. Our screening for Xpr1 variants identified the permissive Xpr1(sxv) allele in 7 strains of laboratory mice, including a Bxv1-positive strain, F/St, which is characterized by lifelong X-MLV viremia. Cells from three strains carrying Xpr1(sxv), namely, SWR, SJL, and SIM.R, were shown to be infectable by X-MLV and XMRV; these strains carry different alleles at Fv1 and vary in their sensitivities to specific X/P-MLV isolates and XMRV. Several strains with Xpr1(sxv) lack the active Bxv1 provirus or other endogenous X-MLVs and may provide a useful model system to evaluate the in vivo spread of these gammaretroviruses and their disease potential in their natural host.
实验鼠携带内源性的嗜性小鼠白血病病毒(X-MLVs),因其不能感染实验鼠的细胞而得名。这种对外源感染的抗性归因于 XPR1 伽马逆转录病毒受体的一种非许可变体,这种抗性也限制了能够产生感染性病毒的生殖系 X-MLV 前病毒在体内的表达。由于实验鼠在其前病毒含量和病毒表达模式方面差异很大,我们筛选了近交系,以寻找 XPR1 受体的序列和功能变体。我们还对近交系和野生鼠种进行了内源性前病毒 Bxv1 的分型,该前病毒能够产生感染性的 X-MLV,并且也是产生致病性重组 MLV 的原因之一。我们在许多常见的近交系和一些日本黑鼠中发现了活跃的 Bxv1 前病毒,但在携带 X-MLV 的其他野生鼠种中均未发现。我们对 Xpr1 变体的筛选在 7 种实验鼠中发现了许可的 Xpr1(sxv)等位基因,包括 Bxv1 阳性的 F/St 株,该株具有终身 X-MLV 病毒血症。来自携带 Xpr1(sxv)的三个株系的细胞,即 SWR、SJL 和 SIM.R,被证明可被 X-MLV 和 XMRV 感染;这些株系在 Fv1 上携带不同的等位基因,并且对特定的 X/P-MLV 分离株和 XMRV 的敏感性也不同。一些带有 Xpr1(sxv)的株系缺乏活跃的 Bxv1 前病毒或其他内源性 X-MLV,它们可能为评估这些伽马逆转录病毒在其自然宿主中的体内传播及其疾病潜力提供一个有用的模型系统。