A Novel Recombinant Retrovirus in the Genomes of Modern Birds Combines Features of Avian and Mammalian Retroviruses

Abstract

Endogenous retroviruses (ERVs) represent ancestral sequences of modern retroviruses or their extinct relatives. The majority of ERVs cluster alongside exogenous retroviruses into two main groups based on phylogenetic analyses of the reverse transcriptase (RT) enzyme. Class I includes gammaretroviruses, and class II includes lentiviruses and alpha-, beta-, and deltaretroviruses. However, analyses of the transmembrane subunit (TM) of the envelope glycoprotein (env) gene result in a different topology for some retroviruses, suggesting recombination events in which heterologous env sequences have been acquired. We previously demonstrated that the TM sequences of five of the six genera of orthoretroviruses can be divided into three types, each of which infects a distinct set of vertebrate classes. Moreover, these classes do not always overlap the host range of the associated RT classes. Thus, recombination resulting in acquisition of a heterologous env gene could in theory facilitate cross-species transmissions across vertebrate classes, for example, from mammals to reptiles. Here we characterized a family of class II avian ERVs, "TgERV-F," that acquired a mammalian gammaretroviral env sequence. Although TgERV-F clusters near a sister clade to alpharetroviruses, its genome also has some features of betaretroviruses. We offer evidence that this unusual recombinant has circulated among several avian orders and may still have infectious members. In addition to documenting the infection of a nongalliform avian species by a mammalian retrovirus, TgERV-F also underscores the importance of env sequences in reconstructing phylogenies and supports a possible role for env swapping in allowing cross-species transmissions across wide taxonomic distances. IMPORTANCERetroviruses can sometimes acquire an envelope gene (env) from a distantly related retrovirus. Since env is a key determinant of host range, such an event affects the host range of the recombinant virus and can lead to the creation of novel retroviral lineages. Retroviruses insert viral DNA into the host DNA during infection, and therefore vertebrate genomes contain a "fossil record" of endogenous retroviral sequences thought to represent past infections of germ cells. We examined endogenous retroviral sequences in avian genomes for evidence of recombination events involving env. Although cross-species transmissions of retroviruses between vertebrate classes (from mammals to birds, for example) are thought to be rare, we here characterized a group of avian retroviruses that acquired an env sequence from a mammalian retrovirus. We offer evidence that this unusual recombinant circulated among songbirds 2 to 4 million years ago and has remained active into the recent past.

Infectious Entry Pathway Mediated by the Human Endogenous Retrovirus K Envelope Protein

“…The broad tropism in mammals is consistent with the known distribution of exogenous betaretroviruses and endogenous betaretrovirus-like sequences in a wide range of mammals. However, while there are ERVs in birds and reptiles that have betaretrovirus-like gag-pol regions, the env genes of these ERVs are more similar to gamma-type env genes, and no true beta-type env has been identified outside of mammals (18,(28)(29)(30)(31). This suggests that restricted tropism is not a general property of beta-type envelopes and that the lack of endogenous beta-type envelopes outside of mammals is not explained solely by ENV tropism.…”

“…Endogenous beta-type envelopes are present in mammals, whereas gamma types are found throughout metazoans (18,28). However, betaretroviral gag-pol regions and gamma-type env genes are present in nonmammalian species (29)(30)(31), suggesting that there may be an ENV-dictated species-specific tropism restriction for beta-type envelopes.…”

Evolution of bird genomes—a transposon's‐eye view

“… reporting dominance of betaretroviruses and gammaretroviruses). Interestingly, in‐depth ERV analysis of the zebra finch genome revealed a recombinant retrovirus that acquired its envelope protein gene from a mammalian gammaretrovirus and underwent recent cross‐species transmissions between oscine passerines, woodpecker, and duck . On the other hand, analysis of the higher copy number solo‐LTRs have yielded insights into LTR accumulation across the avian tree of life.…”

Pushing the endogenous envelope

“…Interestingly, another recombinant ERV comprising a class II gag-pol region with a gamma-type env was recently discovered in the genomes of several avian species [3,68]. In this case, the gag-pol region has features of both alpha- and betaretroviruses, and in phylogenetic analyses is positioned basal to the alpharetroviral clade.…”