Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice using deep sequencing

Abstract

It has recently been reported that the xenotropic murine leukemia virus-related virus (XMRV) derives from a laboratory recombinant. However, sequences with characteristics of the 5' half of XMRV (termed PreXMRV-2) have been identified in several laboratory mouse genomes and cell lines suggesting parts of the XMRV genome exist as naturally occurring retroviruses in mice. We compare here PreXMRV-2 gag sequence diversity in mice to that of reported XMRV-like sequences by testing a panel of wild mouse and common inbred laboratory mouse strain genomic DNAs and by using high throughput amplicon sequencing. Sequences with features typical of previously reported PreXMRV-2 sequences, among them a 24 nt deletion, were repeatedly identified in different wild mice and inbred mouse strains within a high background of non-XMRV-like sequences. However, Sanger sequencing of clones from amplicons failed to retrieve such sequences effectively. Phylogenetic analysis suggests that PreXMRV-2 gag sequences from mice, cell lines and patient samples belong to the same evolutionarily young clade and that such sequences are diverse and widespread within Mus musculus domesticus and laboratory mice derived from this species. No evidence of PreXMRV-2 like gag sequences could be obtained outside of the M. musculus lineage. The results suggest that accurate determination of presence, absence and relationships of specific murine retroviral strains benefit greatly from deep sequencing analysis.