Intact, recombinant, and spliced forms of endogenous mouse mammary tumor viruses in inbred and wild mice.

UNLABELLED

Endogenous retroviruses (ERVs) are chromosomally integrated viral copies that represent relics of past infections. Analysis of the sequenced genomes of 17 mouse strains, subspecies, and identified 29 ERVs of mouse mammary tumor viruses (MMTVs), termed . The 15 laboratory mouse are each present in multiple strains reflecting their common breeding history; most predate the development of inbred strains and were likely acquired by progenitors but have no orthologs in wild mice, whereas four, including the intact , were likely endogenized more recently. One of the 14 found in wild mice was distributed over a broad geographic range in southeast Asia. Most are full-length, with multiple open reading frames, but from many wild mice have an unusual envelope deletion corresponding to an intron of the viral accessory gene, suggesting its derivation from spliced MMTV cDNAs. These deleted have open reading frames, are found in globally distributed mice, and show subspecies-specific sequence variation consistent with their recurrent generation. The highly variable MMTV gene, responsible for resistance to exogenous infection, exhibits evidence of recombination as well as positive selection, consistent with its role in antiviral defense. In contrast, the spread of in populations is not marked by an active arms race pitting the MMTV envelope against its cellular receptor. Thus, the acquisition of potentially disease-inducing is a recent and ongoing process in accompanied by recombination, positive selection, and a recurrent envelope deletion.

IMPORTANCE

Endogenous retroviruses (ERVs) are copies of viral genomes inserted into host chromosomes, producing a fossil record of past infections and virus-host co-adaptations. ERVs of mouse mammary tumor viruses () were found in all common laboratory strains, all subspecies, and a sister species, . Most laboratory mouse predate inbred strain origins and were acquired by , but although widely shared among strains, none of these were found in wild mice. Among wild mouse , only one showed a broad geographic distribution. All subspecies carry with a large envelope deletion corresponding to the processed mRNA for the viral gene; such likely derive from spliced viral mRNA. The gene responsible for resistance to exogenous infection is under purifying selection and has been subject to recombination, whereas the envelope and its cellular receptor show no evidence of genetic conflicts.