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Team Uncovers Ancient Non-Retroviral Virus Sequences in Vertebrate Genomes

By a GenomeWeb staff reporter

NEW YORK (GenomeWeb News) – A study appearing online last night in PLoS Pathogens suggests many vertebrate genomes harbor bits of ancient non-retroviral RNA viruses related to modern-day viruses that can cause hemorrhagic fevers and neurological disease.

Researchers from the Fox Chase Cancer Center in Philadelphia and the Institute for Advanced Study in Princeton looked for nearly 6,000 genes from non-retroviral virus families in the genome sequences of four-dozen vertebrate species. Indeed, the team found that 19 vertebrate genomes contained non-retroviral sequences, all originating from one of two RNA virus groups: the Filovirus (Ebola/Marburg) family and the Bornavirus family.

"Surprisingly, almost all of the nearly 80 [viral] integrations identified are related to only two viral families," the researchers wrote, "the Ebola/Marburgviruses, and the Bornaviruses, which are deadly pathogens that cause lethal hemorrhagic fevers and neurological disease, respectively."

The study suggests "the source of our genetic material is considerably wider than we thought," co-corresponding author Anna Marie Skalka, director emerita at Fox Chase Cancer's Institute for Cancer Research, said in a statement. "It includes our own genes and unexpected viral genes as well."

Past studies have unearthed a slew of retroviral sequences in vertebrate genomes. Because RNA retroviruses are reverse-transcribed into DNA and incorporated into host DNA as part of their replication cycle, finding pieces of them in host genomes hasn't been all that surprising. On the other hand, RNA viruses that don't replicate using a DNA intermediate turn up less frequently in host genomes.

"They replicate their RNA and are not known to make any DNA. And they have no known mechanism for getting their genetic material integrated into the DNA of the host genome," Skalka said in a statement. "Indeed, some of them don't even enter the nucleus when they replicate."

Even so, the researchers noted, there's mounting evidence that non-retroviral sequences can find their way into host genomes as well. For instance, researchers from Japan and the US reported earlier this year that they found non-retroviral, Bornavirus-like elements in mammalian genomes.

In an effort to look for additional single-stranded, non-retroviral RNA viruses in vertebrate genomes, Skalka and her co-workers used the BLAST program and the NCBI's viral Refseq database to search for 5,666 viral genes — representing sequences from all known single stranded RNA, non-retroviral virus families — in the genomes of 48 vertebrate species.

In the process, they found nearly 80 non-retroviral sequences in the genomes of 19 vertebrate species, including sequences resembling the BDV nucleocapsid N gene RNA-dependent RNA polymerase and matrix coding sequences, and more.

Overall, 13 of the 48 vertebrate genomes contained sequences corresponding to sequences from viruses in the Bornavirus family, while six contained Ebola/Marburgvirus family-like sequences.

Based on the sequence data and viral integration patterns in the genomes, the researchers believe RNA viruses were likely reverse transcribed into DNA and hitchhiked into host genomes with a type of mobile sequences called long interspersed nuclear elements or LINE elements.

By comparing the non-retroviral sequence patterns in the genomes of related animals, the team was also able to begin teasing apart the timing of such integration events — which appear to go as far back as about 40 million years ago in some lineages.

More research is needed to understand what function these sequences have in vertebrate genomes, if any, the researchers noted, though at least some of the sequences seem to get expressed.

Based on their comparisons between previously reported non-retroviral infection data and newly detected sequence patterns, the team speculated that such sequences may either help some species resist infection by related RNA viruses, or that the sequences may have become incorporated into the genomes of naturally resistant species.

"The conservation and expression of some of these endogenous sequences, and a potential correlation between their presence and species' resistance to the diseases caused by the related viruses, suggest that they may afford an important selective advantage in these vertebrate populations," the team wrote. "Whether the germline integrations that we have identified are simply accidents or, as we suspect, may sometimes provide the host with an important selectable advantage, can now be tested."

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