Infectious Endogenous Retroviruses in Cats and Emergence of Recombinant Viruses

Abstract

bEndogenous retroviruses (ERVs) comprise a significant percentage of the mammalian genome, and it is poorly understood whether they will remain as inactive genomes or emerge as infectious retroviruses. Although several types of ERVs are present in domestic cats, infectious ERVs have not been demonstrated. Here, we report a previously uncharacterized class of endogenous gammaretroviruses, termed ERV-DCs, that is present and hereditary in the domestic cat genome. We have characterized a subset of ERV-DC proviral clones, which are numbered according to their genomic insertions. One of these, ERV-DC10, located in the q12-q21 region on chromosome C1, is an infectious gammaretrovirus capable of infecting a broad range of cells, including human. Our studies indicate that ERV-DC10 entered the genome of domestic cats in the recent past and appeared to translocate to or reintegrate at a distinct locus as infectious ERV-DC18. Insertional polymorphism analysis revealed that 92 of 244 domestic cats had ERV-DC10 on a homozygous or heterozygous locus. ERV-DC-like sequences were found in primate and rodent genomes, suggesting that these ERVs, and recombinant viruses such as RD-114 and BaEV, originated from an ancestor of ERV-DC. We also found that a novel recombinant virus, feline leukemia virus subgroup D (FeLV-D), was generated by ERV-DC env transduction into feline leukemia virus in domestic cats. Our results indicate that ERV-DCs behave as donors and/or acceptors in the generation of infectious, recombinant viruses. The presence of such infectious endogenous retroviruses, which could be harmful or beneficial to the host, may affect veterinary medicine and public health.

Identification and classification of feline endogenous retroviruses in the cat genome using degenerate PCR and in silico data analysis

“…1). The clone, MJ52, was almost identical (99 % similarity) to ERV-DC10, which has been previously reported to be an infectious ERV in domestic cats (Anai et al, 2012). Another clone MJ62 showed high sequence homology (98 % similarity) to enFeLV-GGAG and enFeLV-AGTT.…”

“…Although there has been a brief report on a genome-level analysis of feline ERVs among reports on the cat genome project (Pontius et al, 2007), only a few types of feline ERV sequences have been reported (Anai et al, 2012;Beyer et al, 1987;Bonner & Todaro, 1979;Haapala et al, 1985;McAllister et al, 1972;Soe et al, 1983;van der Kuyl et al, 1999), and a detailed analysis on feline ERVs at the genome level has not been conducted. Therefore, we aimed to identify retroviral pro/pol-containing sequences in the cat genome and group them into FcERV c, b and -L (spuma-like) families according to the genera classification strategy for retroviruses.…”

“…There is evidence of the presence of recombination between endogenous and exogenous feline ERVs (Anai et al, 2012;Beyer et al, 1987;Chakrabarti et al, 1994;Sheets et al, 1993;Stewart et al, 1986Stewart et al, , 2011. However, we only focused on the classification of FcERV based on the pro/pol region and did not analyse the recombinant forms of ERVs in the cat genome.…”

“…ERVs were also detected based on their homology to synthetic primer binding site probes (Kröger & Horak, 1987) as well as DNA hybridization and sequencing (Dunwiddie et al, 1986;Lueders & Kuff, 1980;Ono et al, 1985). Recently, sufficient data for phylogenetic analyses were successfully obtained by using PCR to directly amplify ERV sequences from the host genomic DNA of pigs (Klymiuk et al, 2002;Patience et al, 2001), sheep (Klymiuk et al, 2003), cattle (Garcia-Etxebarria & Jugo, 2010;Xiao et al, 2008b), dog (Jo et al, 2012) and other vertebrates (Herniou et al, 1998) Several endogenous retroviruses have been detected in the genome of domestic cats (Felis catus); these viruses include endogenous feline leukaemia virus (enFeLV) (Soe et al, 1983), RD-114, a C-type retrovirus (McAllister et al, 1972), MAC-1 primate retrovirus-related virus (Bonner & Todaro, 1979), ECE1 (Beyer et al, 1987), FcEV (van der Kuyl et al, 1999), FERVmlu1 and FERVmlu2 (Yuhki et al, 2008), and ERV-DC (Anai et al, 2012). However, detailed analysis regarding their structural variations, genome-level diversity and their relationships has not been addressed.…”

A Novel Endogenous Betaretrovirus in the Common Vampire Bat (Desmodus rotundus) Suggests Multiple Independent Infection and Cross-Species Transmission Events

“…Little is known about retroviruses in bats from the neotropics, and nothing is known about those in vampire bats. Endogenous retroviruses (ERVs) are present in the genomes of all vertebrates examined (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). As different species may share ERV sequences, it is assumed that, in many cases, an exogenous retrovirus infected the common ancestor of multiple species and became fixed in the genome prior to species divergence (14)(15)(16).…”