Cross-Species Transmission and Differential Fate of an Endogenous Retrovirus in Three Mammal Lineages

Xiaoyu Zhuo,Cédric Feschotte,Robert Belshaw

doi:10.1371/journal.ppat.1005279

Abstract

Endogenous retroviruses (ERVs) arise from retroviruses chromosomally integrated in the host germline. ERVs are common in vertebrate genomes and provide a valuable fossil record of past retroviral infections to investigate the biology and evolution of retroviruses over a deep time scale, including cross-species transmission events. Here we took advantage of a catalog of ERVs we recently produced for the bat Myotis lucifugus to seek evidence for infiltration of these retroviruses in other mammalian species (>100) currently represented in the genome sequence database. We provide multiple lines of evidence for the cross-ordinal transmission of a gammaretrovirus endogenized independently in the lineages of vespertilionid bats, felid cats and pangolin ~13–25 million years ago. Following its initial introduction, the ERV amplified extensively in parallel in both bat and cat lineages, generating hundreds of species-specific insertions throughout evolution. However, despite being derived from the same viral species, phylogenetic and selection analyses suggest that the ERV experienced different amplification dynamics in the two mammalian lineages. In the cat lineage, the ERV appears to have expanded primarily by retrotransposition of a single proviral progenitor that lost infectious capacity shortly after endogenization. In the bat lineage, the ERV followed a more complex path of germline invasion characterized by both retrotransposition and multiple infection events. The results also suggest that some of the bat ERVs have maintained infectious capacity for extended period of time and may be still infectious today. This study provides one of the most rigorously documented cases of cross-ordinal transmission of a mammalian retrovirus. It also illustrates how the same retrovirus species has transitioned multiple times from an infectious pathogen to a genomic parasite (i.e. retrotransposon), yet experiencing different invasion dynamics in different mammalian hosts.

Highlights

Viral cross-species transmission (CST) represents a major threat to both human and animal populations
We investigated past incidents of cross-species transmission involving bat retroviruses, by screening for the presence of endogenous retroviruses (ERVs) previously identified in the genome of the little brown bat in more than 100 diverse mammal species. This screen revealed an intriguing case of a gammaretrovirus that independently infiltrated the germ line of species belonging to three mammalian orders: vesper bat, felid cat and pangolin
We found that the ERV initiated its genomic invasion of the three lineages around the same timeframe ~13–25 million years ago, but experienced a different fate in each lineage

Summary

Introduction

Viral cross-species transmission (CST) represents a major threat to both human and animal populations. Most viral diseases of humans are zoonotic: they stem from CST of viruses from domestic or wild animals [1]. The explosion and development of human society, including modern transportation, over the last 100 years has exposed us to an increasing number of pathogens [2]. The pathogens causing AIDS (HIV-1 and HIV-2) are retroviruses, a family of RNA viruses that use reverse transcription to replicate their genome [5]. Other retroviral CST events have been documented within primates, felids and ruminants, suggesting that retroviral CST represents a continuous threat to human and animal health [6,7,8,9,10]

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