Multiple Groups of Endogenous Betaretroviruses in Mice, Rats, and Other Mammals

Abstract

Betaretroviruses exist in endogenous and exogenous forms in hosts that are widely distributed and evolutionarily distantly related. Here we report the discovery and characterization of several previously unknown betaretrovirus groups in the genomes of Mus musculus and Rattus norvegicus. Each group contains both mouse and rat elements, and several of the groups are more closely related to previously known betaretroviruses from nonmurine hosts. Some of the groups also include members from hosts which were not previously known to harbor betaretroviruses, such as the gray mouse lemur (Microcebus murinus) and Seba's short-tailed bat (Carollia perspicillata). Some of the mouse and rat elements possess intact open reading frames for gag, pro, pol, and/or env genes and display characteristics of having retrotransposed recently. We propose a model whereby betaretroviruses have been evolving within the genomes of murid rodents for at least the last 20 million years and, subsequent to (or concomitant with) the global spread of their murid hosts, have occasionally been transmitted to other species.Endogenous retroviruses are present in the genomes of all vertebrates (5). They are presumed to arise from germ line infection by exogenous retroviruses, although factors controlling endogenization are poorly understood. Endogenous proviruses accumulate mutations while in the germ line but can occasionally escape the germ line and infect other hosts, sometimes following recombination with other endogenous or exogenous retroviruses (5,20).The Betaretrovirus genus includes the viruses formerly known as type B and type D retroviruses (33). Betaretroviruses have been discovered in mammalian hosts of wide geographical and evolutionary diversity (Table 1). Mouse mammary tumor virus (MMTV), the prototype type B retrovirus, exists in closely related endogenous and exogenous forms, with variable distribution in both laboratory strains and wild species of mice (6,7,11,14). Jaagsiekte sheep retrovirus (JSRV), enzootic nasal tumor virus (ENTV), and endogenous sheep retrovirus are closely related endogenous and exogenous retroviruses of sheep and goats (9,12,35 (18), and a metatherian (marsupial) mammal, the Australian common brushtail possum (Trichosurus vulpecula endogenous retrovirus type D [TvERV-D]) (1). PCR approaches, using degenerate primers based on conserved regions of the retroviral pro and/or pol genes, have also been used to detect betaretrovirus-related elements in the genomes of pigs (10, 22), the bower bird, and the stripe-faced dunnart (13), although these elements have not been completely characterized. Many of the endogenous betaretroviruses appear to have entered the genomes of their hosts relatively recently (within the last ϳ10 million years) (Table 1). However, no satisfactory explanation as to how betaretroviruses could have become so widely distributed has been presented.The Muridae family of rodents comprises over 1,300 species and contains approximately one-quarter of all the known mammalian species (21). The family ...

A novel active endogenous retrovirus family contributes to genome variability in rat inbred strains

“…Earlier reports of recent insertions of ERV sequences suggested that active copies of ERVs might exist in rat populations (Xiao et al 1995;Baillie et al 2004). Here, we identified a novel, active family of ERVs in the rat genome, RnERV-K8e, that was discovered as a recent mutagenic insertion in the Cntrob gene associated with the hd phenotype (Liška et al 2009).…”

“…Indeed, a functional L1 retrotransposon has been identified in rat chloroleukemia cells (Servomaa and Rytomaa 1990;Kirilyuk et al 2008). Furthermore, elements identified in silico might add to the list of potentially active ERVs (Baillie et al 2004;Gibbs et al 2004). In addition to autonomous elements, SINE mobilization might also contribute to insertional polymorphism (Gibbs et al 2004).…”

“…2A) revealed that the Cntrob-element clusters together with the poorly characterized MnERVK10c family in mouse, and does not group together with the IAP elements. Both the Cntrob-and the IAP elements form a cluster separate from b-ERVs, where the potentially autonomous RnERV-b5 (Baillie et al 2004) is grouped ( Fig. 2A).…”

“…1C). In addition to the ERV inserted into Cntrob, other ERVs, including IAP elements (Furter et al 1989), as well as numerous ERV subfamilies of b-retroviruses have been reported from both the rat and mouse genomes (Baillie et al 2004). Phylogenetic analysis based on nucleotide sequence alignments of retroviral pol genes of both exogenous retroviruses and ERVs ( Fig.…”

“…However, all of the reported transcripts or novel insertions of rat ERV elements are fragmented, and contain inactivating mutations. In silico searches identified several families that belong to b-ERVs in the rat genome, including the young, potentially autonomous Rattus norvegicus RnERV-b5 elements (Baillie et al 2004). Furthermore, in silico sequence analyses predicted two ERV1, as well as four ERV2 families, that may still be active in rats (Gibbs et al 2004).…”