The classical laboratory mouse strains are genetic mosaics of three Mus musculus subspecies that occupy distinct regions of Eurasia. These strains and subspecies carry infectious and endogenous mouse leukemia viruses (MLVs) that can be pathogenic and mutagenic. MLVs evolved in concert with restrictive host factors with some under positive selection, including the XPR1 receptor for xenotropic/polytropic MLVs (X/P-MLVs) and the post-entry restriction factor Fv1. Since positive selection marks host-pathogen genetic conflicts, we examined MLVs for counter-adaptations at sites that interact with XPR1, Fv1, and the CAT1 receptor for ecotropic MLVs (E-MLVs). Results describe different co-adaptive evolutionary paths within the ranges occupied by these virus-infected subspecies. The interface of CAT1, and the otherwise variable E-MLV envelopes, is highly conserved; antiviral protection is afforded by the Fv4 restriction factor. XPR1 and X/P-MLVs variants show coordinate geographic distributions, with receptor critical sites in envelope, under positive selection but with little variation in envelope and XPR1 in mice carrying P-ERVs. The major Fv1 target in the viral capsid is under positive selection, and the distribution of Fv1 alleles is subspecies-correlated. These data document adaptive, spatial and temporal, co-evolutionary trajectories at the critical interfaces of MLVs and the host factors that restrict their replication.

中文翻译：

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小鼠 Gammaretroviruses 和三个限制性宿主因素的跨时空协同进化适应模式

经典的实验室小鼠品系是占据欧亚大陆不同区域的三个小家鼠亚种的遗传马赛克。这些菌株和亚种携带具有致病性和致突变性的传染性和内源性小鼠白血病病毒 (MLV)。MLV 与限制性宿主因子协同进化，其中一些处于正选择状态，包括异性/多向性 MLV (X/P-MLV) 的 XPR1 受体和进入后限制因子Fv1. 由于正选择标志着宿主-病原体遗传冲突，我们检查了 MLV 在与 XPR1、Fv1 和生态 MLV (E-MLV) 的 CAT1 受体相互作用的位点的反适应。结果描述了这些病毒感染亚种所占据的范围内的不同共同适应进化路径。CAT1 的接口，以及其他可变的 E-MLV 包络，是高度保守的；Fv4限制因子提供抗病毒保护。XPR1 和 X/P-MLVs 变体显示出协调的地理分布，受体关键位点位于包膜中，在正选择下，但携带 P-ERV 的小鼠的包膜和 XPR1 几乎没有变化。病毒衣壳中的主要 Fv1 靶点处于正选择状态，Fv1的分布等位基因是亚种相关的。这些数据记录了 MLV 关键接口处的自适应、空间和时间、共同进化轨迹以及限制其复制的宿主因素。