Structures of Endogenous Nonecotropic Murine Leukemia Virus (MLV) Long Terminal Repeats in Wild Mice: Implication for Evolution of MLVs

To develop a better understanding of the interaction between retroviruses and their hosts, we have investigated the polymorphism in endogenous murine leukemia proviruses (MLVs). We used genomic libraries of wild mouse DNAs and PCR to analyze genetic variation in the proviruses found in wild mouse species, including Mus musculus (M. m. castaneus, M. m. musculus, M. m. molossinus, and M. m. domesticus), Mus spretus, and Mus spicelegus, as well as some inbred laboratory strains. In this analysis, we detected several unique forms of sequence organization in the U3 regions of the long terminal repeats of these proviruses. The distribution of the proviruses with unique U3 structures demonstrated that xenotropic MLV-related proviruses were present only in M. musculus subspecies, while polytropic MLV-related proviruses were found in both M. musculus and M. spretus. Furthermore, one unique provirus from M. spicelegus was found to be equidistant from ecotropic provirus and nonecotropic provirus by phylogenetic analysis. This provirus, termed HEMV, was thus likely to be related to the common ancestor of these MLVs. Moreover, an ancestral type of polytropic MLV-related provirus was detected in M. spretus species. Despite their "ancestral" phylogenetic position, proviruses of these types are not widespread in mice, implying more-recent spread by infection rather than inheritance. These results imply that recent evolution of these proviruses involved alternating periods of replication as virus and residence in the germ line.