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New Study Reveals Extensive Retroviral Activity Across Vertebrates

NEW YORK (GenomeWeb) – Despite the extensive research that has been conducted on retroviruses, little has been discovered about the interactions between these pathogens and their vertebrate hosts that have occurred over millions of years.

But by scanning the genomes of dozens of vertebrates, a Swedish research team has been able to construct a record of host-retrovirus interactions and gain new insights into retroviral evolution, diversity, host switching, and the factors influencing retroviral transmission.

"Our study shows that endogenous retroviruses are incredibly common in vertebrate hosts," Patric Jern, an Uppsala University researcher who participated in the study, told GenomeWeb in an email, noting that none of the host species studied have completely escaped retroviral activity.

Taken together, the findings are expected to guide future studies of retrovirus biology by illustrating the major patterns of retrovirus evolution, the scientists wrote in their report, which appeared in the Proceedings of the National Academy of Sciences. In terms of human health, they could also aid in evaluating the effects of viruses on host functions and disease, Jern added.

Retroviruses are enveloped RNA viruses that replicate via reverse transcription, with RNA transforming into DNA and then incorporating into the host cell's genome. New viruses are then produced using host cellular resources.

While advances in molecular biology have been made through the study of retroviruses, such as the discovery of reverse transcriptase, key aspects of retrovirus biology remain unclear including their origin and diversity, evolutionary patterns of host use, and mechanism underlying their transmission.

To address these knowledge gaps, scientists from Uppsala University and Lund University developed a strategy to examine the co-evolution of retroviruses and their hosts by looking to endogenous retroviruses (ERVs).

Occasionally, the proviral DNA insertions that characterize retrovirus replication will occur in a germline cell, and as a result the integrated retrovirus can be inherited down the host lineage in which is known as an ERV. After the millions of years of this occurring, there are large portions of vertebrate genomes that derive from ERVs — an estimated 8 percent, in the case of humans — which represent a kind of "snapshot of retroviral evolution" at the time of integration, according to Jern and his team.

Taking advantage of recent whole-genome sequencing projects and accessing high-performance computer clusters, the researchers mined a set of 65 vertebrate genomes for ERVs, initially investigating retroviral origin and diversity by estimating retroviral phylogeny and quantifying ERV abundance across different hosts.

Of the roughly 94,000 ERVs they detected, about 36,000 were deemed high-quality given their relatively complete sequences with little to moderate mutational degradation, according to the PNAS study. To address high sequence divergence and allow homology estimation among sequences across retroviral groups, the scientists analyzed conserved regions samples from multiple locations across the retroviral genome.

Their analysis revealed a large diversity of ERVs, with retroviral sequences far more widespread across vertebrates than previously believed, Jern stated. Further, the majority of ERV clades recovered did not contain known retroviruses, indicating that retroviral lineages are either short-lived over evolutionary time or the existence of a considerable number of yet-to-be-identified retroviruses.

The study also showed retroviruses to be "exceptional host generalists, having the ability to switch among distantly related vertebrate hosts," he added.

In looking for host factors that influence retroviral transmission, the Lund and Uppsala investigators found that internal fertilization was the only single life-history character that correlated strongly with total ERV abundance in host genomes.

They urged caution when interpreting this particular finding, however, citing the small number of independent evolutionary origins of external fertilization among the vertebrates included in their work, as well as the possibility of currently unmeasured ecological traits that could underlie this finding.

"Thus, the inclusion of additional hosts, particularly amphibians and additional internally fertilizing fishes, together with the analysis of further hosts traits, will be useful in future studies," they wrote.

Although most virology research has focused on humans and domestic and laboratory animals, the authors noted that their findings demonstrate that a great number of retroviruses have invaded the germ line across different vertebrates. Given the health implications of zoonoses such as Ebola virus and HIV, "analyses of ERV population genomics across diverse vertebrate species within a phylogenetic context may offer an important means of estimating extant retroviral diversity and potentially avoiding future retroviral transmission to humans," they added.