Tracking the Fate of Endogenous Retrovirus Segregation in Wild and Domestic Cats

Abstract

Endogenous retroviruses (ERVs) of domestic cats (ERV-DCs) are one of the youngest feline ERV groups in domestic cats (Felis silvestris catus); some members are replication competent (ERV-DC10, ERV-DC18, and ERV-DC14), produce the antiretroviral soluble factor Refrex-1 (ERV-DC7 and ERV-DC16), or can generate recombinant feline leukemia virus (FeLV). Here, we investigated ERV-DC in European wildcats (Felis silvestris silvestris) and detected four loci: ERV-DC6, ERV-DC7, ERV-DC14, and ERV-DC16. ERV-DC14 was detected at a high frequency in European wildcats; however, it was replication defective due to a single G → A nucleotide substitution, resulting in an E148K substitution in the ERV-DC14 envelope (Env). This mutation results in a cleavage-defective Env that is not incorporated into viral particles. Introduction of the same mutation into feline and murine infectious gammaretroviruses resulted in a similar Env dysfunction. Interestingly, the same mutation was found in an FeLV isolate from naturally occurring thymic lymphoma and a mouse ERV, suggesting a common mechanism of virus inactivation. Refrex-1 was present in European wildcats; however, ERV-DC16, but not ERV-DC7, was unfixed in European wildcats. Thus, Refrex-1 has had an antiviral role throughout the evolution of the genus Felis, predating cat exposure to feline retroviruses. ERV-DC sequence diversity was present across wild and domestic cats but was locus dependent. In conclusion, ERVs have evolved species-specific phenotypes through the interplay between ERVs and their hosts. The mechanism of viral inactivation may be similar irrespective of the evolutionary history of retroviruses. The tracking of ancestral retroviruses can shed light on their roles in pathogenesis and host-virus evolution. IMPORTANCE Domestic cats (Felis silvestris catus) were domesticated from wildcats approximately 9,000 years ago via close interaction between humans and cats. During cat evolution, various exogenous retroviruses infected different cat lineages and generated numerous ERVs in the host genome, some of which remain replication competent. Here, we detected several ERV-DC loci in Felis silvestris silvestris. Notably, a species-specific single nucleotide polymorphism in the ERV-DC14 env gene, which results in a replication-defective product, is highly prevalent in European wildcats, unlike the replication-competent ERV-DC14 that is commonly present in domestic cats. The presence of the same lethal mutation in the env genes of both FeLV and murine ERV provides a common mechanism shared by endogenous and exogenous retroviruses by which ERVs can be inactivated after endogenization. The antiviral role of Refrex-1 predates cat exposure to feline retroviruses. The existence of two ERV-DC14 phenotypes provides a unique model for understanding both ERV fate and cat domestication.

Copy Number and Prevalence of Porcine Endogenous Retroviruses (PERVs) in German Wild Boars

“…Among all species, chicken, mice, and cats are best analyzed concerning the endogenous retroviruses in their genomes. For example, during cat evolution various exogenous retroviruses infected different cat lineages and generated numerous endogenous retroviruses in the host genome, some of which remain replication competent [32]. These viruses also can recombine and integrate de novo.…”

A 192 bp ERV fragment insertion in the first intron of porcine TLR6 may act as an enhancer associated with the increased expressions of TLR6 and TLR1

“…Genome-wide association studies revealed an intronic Alu insertion polymorphism in CD58 gene associated with multiple sclerosis risk possibly due to altering its mRNA splicing [ 30 , 31 ]. In domestic animals, RIPs also have been used for evolution and population genetic analysis in sheep [ 32 ], cat [ 33 ], chicken [ 34 ], and rabbit [ 35 ]. Several RIPs have been associated with phenotypic variation in farm animals, such as an ERV insertion in the 5’ flanking region of SLCO1B3 causing blue eggshell by promoting the expression of the SLCO1B3 gene in the uterus (shell gland) of the oviduct in chicken [ 36 , 37 ], the henny feathering allele harboring an insertion of an intact avian ERV at the 5'end of CYP19A1 [ 38 ], and the SINE insertions in the follicle stimulating hormone beta ( FSHβ) and the protein disulfide isomerase associated 4 ( PDIA4 ) genes associated with litter size variations in pigs [ 39 , 40 ].…”

Management of Suspected Cases of Feline Immunodeficiency Virus Infection in Eurasian Lynx (Lynx lynx) During an International Translocation Program

“…There was a very limited RT activity in the lynx samples when compared to the result of the latent infected domestic cat. Low activity could also be ascribed to an unrevealed endogenous retrovirus (ERV) ( 87 , 88 ). Furthermore, emergence of three FIV-seropositive lynx by WB in the same area (Jura North) nearly at the same time (2016–2017) can hardly be coincidental.…”