title: Sequence Diversity, Intersubgroup Relationships, and Origins of the Mouse Leukemia Gammaretroviruses of Laboratory and Wild Mice.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
authors: Devinka
authors: D
authors: Bamunusinghe
authors: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
authors: Zohreh
authors: Z
authors: Naghashfar
authors: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
authors: Alicia
authors: A
authors: Buckler-White
authors: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
authors: Ronald
authors: R
authors: Plishka
authors: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
authors: Surendranath
authors: S
authors: Baliji
authors: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
authors: Qingping
authors: Q
authors: Liu
authors: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
authors: Joshua
authors: J
authors: Kassner
authors: Bioinformatics and Computational Biosciences Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
authors: Andrew J
authors: AJ
authors: Oler
authors: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
authors: Janet
authors: J
authors: Hartley
authors: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA ckozak@niaid.nih.gov.
authors: Christine A
authors: CA
authors: Kozak
mesh_terms: D000818:Animals; D000830:Animals, Laboratory / Q000821:virology; D000835:Animals, Wild / Q000821:virology; D001483:Base Sequence; D015751:Genes, pol; D014644:Genetic Variation; D016679:Genome, Viral; D009052:Leukemia Virus, Murine / Q000145:classification / Q000235:genetics*; D051379:Mice / Q000235:genetics / Q000821:virology*; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D012367:RNA, Viral; D017423:Sequence Analysis, RNA
chemical_list: D012367:RNA, Viral