Bamunusinghe Devinka, Naghashfar Zohreh, Buckler-White Alicia, Plishka Ronald, Baliji Surendranath, Liu Qingping, Kassner Joshua, Oler Andrew J, Hartley Janet, Kozak Christine A
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
J Virol. 2016 Mar 28;90(8):4186-98. doi: 10.1128/JVI.03186-15. Print 2016 Apr.
Mouse leukemia viruses (MLVs) are found in the common inbred strains of laboratory mice and in the house mouse subspecies ofMus musculus Receptor usage and envelope (env) sequence variation define three MLV host range subgroups in laboratory mice: ecotropic, polytropic, and xenotropic MLVs (E-, P-, and X-MLVs, respectively). These exogenous MLVs derive from endogenous retroviruses (ERVs) that were acquired by the wild mouse progenitors of laboratory mice about 1 million years ago. We analyzed the genomes of seven MLVs isolated from Eurasian and American wild mice and three previously sequenced MLVs to describe their relationships and identify their possible ERV progenitors. The phylogenetic tree based on the receptor-determining regions ofenvproduced expected host range clusters, but these clusters are not maintained in trees generated from other virus regions. Colinear alignments of the viral genomes identified segmental homologies to ERVs of different host range subgroups. Six MLVs show close relationships to a small xenotropic ERV subgroup largely confined to the inbred mouse Y chromosome.envvariations define three E-MLV subtypes, one of which carries duplications of various sizes, sequences, and locations in the proline-rich region ofenv Outside theenvregion, all E-MLVs are related to different nonecotropic MLVs. These results document the diversity in gammaretroviruses isolated from globally distributedMussubspecies, provide insight into their origins and relationships, and indicate that recombination has had an important role in the evolution of these mutagenic and pathogenic agents.
Laboratory mice carry mouse leukemia viruses (MLVs) of three host range groups which were acquired from their wild mouse progenitors. We sequenced the complete genomes of seven infectious MLVs isolated from geographically separated Eurasian and American wild mice and compared them with endogenous germ line retroviruses (ERVs) acquired early in house mouse evolution. We did this because the laboratory mouse viruses derive directly from specific ERVs or arise by recombination between different ERVs. The six distinctively different wild mouse viruses appear to be recombinants, often involving different host range subgroups, and most are related to a distinctive, largely Y-chromosome-linked MLV ERV subtype. MLVs with ecotropic host ranges show the greatest variability with extensive inter- and intrasubtype envelope differences and with homologies to other host range subgroups outside the envelope. The sequence diversity among these wild mouse isolates helps define their relationships and origins and emphasizes the importance of recombination in their evolution.
小鼠白血病病毒（MLV）存在于实验室小鼠的常见近交系以及小家鼠（Mus musculus）的家鼠亚种中。受体使用情况和包膜（env）序列变异在实验室小鼠中定义了三个MLV宿主范围亚组：亲嗜性、多嗜性和异嗜性MLV（分别为E-MLV、P-MLV和X-MLV）。这些外源性MLV源自约100万年前实验室小鼠的野生小鼠祖先获得的内源性逆转录病毒（ERV）。我们分析了从欧亚和美洲野生小鼠中分离出的7种MLV的基因组以及3种先前测序的MLV，以描述它们之间的关系并确定其可能的ERV祖先。基于env受体决定区构建的系统发育树产生了预期的宿主范围聚类，但这些聚类在由病毒其他区域构建的树中并未保持。病毒基因组的共线性比对确定了与不同宿主范围亚组的ERV的片段同源性。6种MLV与一个主要局限于近交小鼠Y染色体的小型异嗜性ERV亚组关系密切。env变异定义了三种E-MLV亚型，其中一种在env富含脯氨酸区域携带不同大小、序列和位置的重复。在env区域之外，所有E-MLV都与不同的非亲嗜性MLV相关。这些结果证明了从全球分布的小家鼠亚种中分离出的γ逆转录病毒的多样性，深入了解了它们的起源和关系，并表明重组在这些诱变和致病因子的进化中发挥了重要作用。
实验室小鼠携带从其野生小鼠祖先获得的三个宿主范围组的小鼠白血病病毒（MLV）。我们对从地理上分离的欧亚和美洲野生小鼠中分离出的7种感染性MLV的完整基因组进行了测序，并将它们与小家鼠进化早期获得的内源性种系逆转录病毒（ERV）进行了比较。我们这样做是因为实验室小鼠病毒直接源自特定的ERV，或者是由不同ERV之间的重组产生的。这六种明显不同的野生小鼠病毒似乎是重组体，通常涉及不同的宿主范围亚组，并且大多数与一种独特的、主要与Y染色体相关的MLV ERV亚型有关。具有亲嗜性宿主范围的MLV表现出最大的变异性，在亚型间和亚型内包膜存在广泛差异，并且在包膜之外与其他宿主范围亚组具有同源性。这些野生小鼠分离株之间的序列多样性有助于确定它们的关系和起源，并强调了重组在其进化中的重要性。
