Abstract
Author SummaryRetroviruses are characterized by their ability to insert a DNA copy of their genome into the chromosomes of infected cells. Occasionally, retroviruses insert into “germline” cells and are subsequently inherited as host alleles called endogenous retroviruses (ERVs). Vertebrate genomes contain thousands of ERV sequences derived from ancient retroviruses, and these viral sequences serve as molecular “fossils” that can be used to explore how retroviruses have evolved over millions of years. Here we combine an analysis of the retroviral “fossil record” with a phylogenetic and historical investigation to determine the origin of a group of avian retroviruses called reticuloendotheliosis viruses (REVs). We present evidence to demonstrate that rather than arising from natural infections of birds, REVs are in fact derived from mammalian retroviruses that were accidentally introduced into avian hosts during experimental studies of a malaria parasite in the late 1930s. Remarkably, REVs have subsequently inserted into the genomes of two large DNA viruses that infect birds, generating chimeric viruses that now circulate naturally in poultry and wild birds.
Highlights
The reticuloendotheliosis viruses (REVs) comprise several closely related amphotropic retroviruses isolated from birds [1]
Vertebrate genomes contain thousands of endogenous retrovirus (ERV) sequences derived from ancient retroviruses, and these viral sequences serve as molecular ‘‘fossils’’ that can be used to explore how retroviruses have evolved over millions of years
We present evidence to demonstrate that rather than arising from natural infections of birds, REVs are derived from mammalian retroviruses that were accidentally introduced into avian hosts during experimental studies of a malaria parasite in the late 1930s
Summary
The reticuloendotheliosis viruses (REVs) comprise several closely related amphotropic retroviruses (family Retroviridae) isolated from birds [1]. Infection is associated with a range of disease syndromes, including anemia, immunosuppression, neoplasia, runting, and feathering abnormalities called ‘‘nakanuke.’’ The etiology of REV infection remains enigmatic— antibodies to REV are widespread in poultry, REV outbreaks occur only sporadically and are relatively rare [3] All retroviruses replicate their genomes via a DNA intermediate that is integrated into the nuclear DNA of the host cell and is referred to as a ‘‘provirus.’’ Occasionally, infection of germ cells allows retroviral proviruses to enter the host germline, so that they can be vertically inherited as host alleles, called endogenous retroviruses (ERVs) [4], a proportion of which end up becoming fixed in the germline. This discovery reinforced the conclusions of earlier, serological studies, which proposed REVs to have originated in mammals [10]
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