Patterns of Coevolutionary Adaptations across Time and Space in Mouse Gammaretroviruses and Three Restrictive Host Factors

Abstract

The classical laboratory mouse strains are genetic mosaics of three Mus musculus subspecies that occupy distinct regions of Eurasia. These strains and subspecies carry infectious and endogenous mouse leukemia viruses (MLVs) that can be pathogenic and mutagenic. MLVs evolved in concert with restrictive host factors with some under positive selection, including the XPR1 receptor for xenotropic/polytropic MLVs (X/P-MLVs) and the post-entry restriction factor Fv1. Since positive selection marks host-pathogen genetic conflicts, we examined MLVs for counter-adaptations at sites that interact with XPR1, Fv1, and the CAT1 receptor for ecotropic MLVs (E-MLVs). Results describe different co-adaptive evolutionary paths within the ranges occupied by these virus-infected subspecies. The interface of CAT1, and the otherwise variable E-MLV envelopes, is highly conserved; antiviral protection is afforded by the Fv4 restriction factor. XPR1 and X/P-MLVs variants show coordinate geographic distributions, with receptor critical sites in envelope, under positive selection but with little variation in envelope and XPR1 in mice carrying P-ERVs. The major Fv1 target in the viral capsid is under positive selection, and the distribution of Fv1 alleles is subspecies-correlated. These data document adaptive, spatial and temporal, co-evolutionary trajectories at the critical interfaces of MLVs and the host factors that restrict their replication.

Inference of selective forces on house mouse genomes during secondary contact in East Asia

“…Previous studies have demonstrated that the Fv1 b allele, which lacks the 1.3-kb deletion commonly found in the subspecies domesticus and musculus, is observed with high frequency in the subspecies castaneus and Japanese samples (Boso et al 2021). We confirmed that the deletion started from Chr4:147,870,288 (GRCm38) and was 1.2 kb in length, resulting in truncation of the C-terminal region of Fv1 (Supplemental Method 4).…”

Inference of Selective Force on House Mouse Genomes during Secondary Contact in East Asia

“…Indeed, our screening accurately identified the retroelement-like Fv1 (Friend virus susceptibility protein 1) gene, an antiviral factor (Best et al 1996) as an castaneus -ancestry enriched gene in Japan. Previous studies have demonstrated that the Fv1 b allele, which lacks the 1.3-kb-length deletion commonly found in the subspecies domesticus and musculus , is observed with high frequency in the subspecies castaneus and the Japanese samples (Boso et al 2021). We confirmed that the deletion started from chr4:147,870,288 (GRCm38) and had 1.2 kb in length, resulting in the truncation of C-terminal region of Fv1 .…”

Unique Structure and Distinctive Properties of the Ancient and Ubiquitous Gamma-Type Envelope Glycoprotein

“…There are a few studies that have examined the potential impact of gammretroviruses on the evolution of the genes that encode their cognate receptors [ 249 , 250 , 251 ]. There are now several examples of SLC receptors that are used by multiple retroviruses ( Table 1 ), as well as cases where the receptors used in the deep past by ancient ERV Env have been identified [ 50 , 72 , 188 , 206 , 214 , 221 , 222 ].…”