Study of virus fossils offers clues to surviving infection

Vladimir A. Belyi , a biologist in Princeton, was lead author.
Vladimir A. Belyi , a biologist in Princeton, was lead author.
Posted: July 30, 2010

Most creatures, if they leave behind evidence of their existence, do so in the form of fossils buried in the earth. Viruses, on the other hand, can leave genetic "fossils" woven into the DNA of animals that they have infected - accounting for a surprising 8 percent of the genome in humans, for example.

A new study has identified animal species that harbor fossils from two especially nasty virus families, one of which includes Ebola, offering intriguing clues as to why some animals can survive infection by these killers and others cannot.

The research, published Thursday in the journal PLoS Pathogens, was a collaboration between Fox Chase Cancer Center and the Institute for Advanced Study in Princeton, the independent academic center where Albert Einstein once hung his hat.

By comparing viral "insertions" that occurred in closely related animal species, the authors determined that some of these traces of past infections were left behind as long as 40 million years ago.

The research drew praise from W. Ian Lipkin, director of the Center for Infection and Immunity at Columbia University's Mailman School of Public Health.

"It has profound implications for understanding how we've evolved with viruses and how viruses have molded us to become what we are today," said Lipkin, who was not involved with the study. "It's like doing genomic archaeology."

Genetic sequences from the filovirus family - the one that includes Ebola and its deadly cousin, Marburg - were found in six vertebrate species. These included the wallaby, the opossum, and a kind of bat called the microbat, but not humans. Ebola and Marburg both cause hemorrhagic fevers.

Sequences from Bornaviruses, which cause neurological disease, were found in the genomes of 13 animal species, including humans, squirrels, and mice.

The researchers found that sequences from the ancient viruses were about 30 percent or 40 percent similar to their modern counterparts, a surprisingly high rate, according to Cedric Feschotte, a University of Texas scientist who was not involved with the paper.

"You would never expect to see anything that close," said Feschotte, an associate professor of biology at UT's Arlington campus.

The high rate of similarity might indicate that some of these ancient viral insertions provide a measure of protection against disease, said Anna Marie Skalka, one of the paper's authors and director emerita of the Institute for Cancer Research at Fox Chase.

"We have conservation of long segments over millions of years, which you would not expect unless there was some advantage, either a while ago or even up to recent times," Skalka said.

"They are under selection," said first author Vladimir A. Belyi, a computational biologist at the institute in Princeton. "That suggests they have a beneficial role."

Further evidence for a protective effect lies in the fact that certain animals with genetic traces of an ancient virus are not susceptible to the modern disease, Skalka said.

Humans, for example, are apparently resistant to Bornaviruses but are very susceptible to Ebola.

And some bats can be infected with Ebola without showing symptoms of the disease - suggesting that these creatures are natural "reservoirs" for the virus.

It's not entirely clear exactly how the protective effect would work - that is, how animals could resist modern-day infections because their genomes contained remnants of an infection from millions of years ago.

Nevertheless, the information might prove useful in developing vaccines, said Skalka, who also was joined in the research by Arnold J. Levine of the institute in Princeton.

The types of viruses examined in the paper are RNA viruses, ranging from influenza to the tropical Dengue virus. They do not make any DNA during replication, so it is not entirely clear how they inserted material into host animals' DNA.

Two papers earlier this year also found evidence of RNA virus genes being inserted, but the new paper is more comprehensive. The authors searched the genomes of 48 vertebrate species, looking for a total of 5,666 viral genes from dozens of virus families. Almost all of the matches came from the Ebola-Marburg family or the Bornaviruses.

Contact staff writer Tom Avril

at 215-854-2430 or

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