Origins of the endogenous and infectious laboratory mouse gammaretroviruses

Abstract

The mouse gammaretroviruses associated with leukemogenesis are found in the classical inbred mouse strains and in house mouse subspecies as infectious exogenous viruses (XRVs) and as endogenous retroviruses (ERVs) inserted into their host genomes. There are three major mouse leukemia virus (MuLV) subgroups in laboratory mice: ecotropic, xenotropic, and polytropic. These MuLV subgroups differ in host range, pathogenicity, receptor usage and subspecies of origin. The MuLV ERVs are recent acquisitions in the mouse genome as demonstrated by the presence of many full-length nondefective MuLV ERVs that produce XRVs, the segregation of these MuLV subgroups into different house mouse subspecies, and by the positional polymorphism of these loci among inbred strains and individual wild mice. While some ecotropic and xenotropic ERVs can produce XRVs directly, others, especially the pathogenic polytropic ERVs, do so only after recombinations that can involve all three ERV subgroups. Here, I describe individual MuLV ERVs found in the laboratory mice, their origins and geographic distribution in wild mouse subspecies, their varying ability to produce infectious virus and the biological consequences of this expression.

Figure 1

Endogenous and exogenous MuLVs. (A) Genomic structure of MuLV ERVs. (B) Phylogenetic tree of MuLV env receptor binding domains (RBDs) constructed using the neighbor-joining method [11] and inferred from 500 replicates using MEGA6 [12]. White ovals represent exogenous viruses; black ovals are active ERVs that produce viral proteins or infectious viruses; the rest are ERVs with unknown expression.

Figure 2

Geographic distribution of XP-MuLV infected house mouse subspecies. The three blue color blocks represent the ranges of the three subspecies carrying predominantly X-MuLVs; green represents P-MuLV infected M. m. domesticus. Wild-caught American house mice are largely domesticus.