George Mason University

By Michele McDonald

Mason researcher and bioinformatics professor Donald Seto is uncovering the secrets of a highly contagious microbe dubbed the “uncommon cold virus.”

Seto is showing how human adenoviruses evolve and can jump from animals to humans, swapping genome pieces with each other to form new and potentially more virulent forms. He’s also changed the way the viruses are studied, colleagues say.

Mason researcher Donald Seto works with graduate students Amir Shams and visiting professor Shoaleh Dehghan. Photo by Evan Cantwell.

These viruses hit the respiratory and gastrointestinal systems, as well as the eyes, where they can cause blindness. They can run rampant through crowded communities, including boarding schools, senior citizen facilities, and U.S. military training bases.

Fears of SARS (severe acute respiratory syndrome) sprang up in China earlier this year when several hundred people became sick. Seto showed the illness wasn’t caused by SARS but by an adenovirus, known by the moniker Ad55.

Adenoviruses frequently go unreported because in a healthy population they generally make people feel miserable but don’t kill them. “Usually people go home or go to work where they spread the virus,” says Seto, a professor in the College of Science’s Bioinformatics and Computational Biology Department.

Others don’t fare so well. People with HIV, as well as other immunocompromised patients such as those with organ transplants, are vulnerable to virulent adenoviruses. In these cases, adenovirus infections often lead to deaths.

Mason researcher Donald Seto is a world expert in the genomic sequencing of adenoviruses. Photo by Evan Cantwell.

The military is a hot spot for these bugs. For example, a new cohort of trainees arrives every five weeks at the U.S. Air Force training camp.

“They live in the same dorms, they eat together, and they train together,” Seto says. “It’s a closely interacting population, and they’re all stressed out. If someone brings in an adenovirus, almost everyone gets sick. It’s a major problem that has cost the military millions [of dollars] and years to solve.”

Little is known about these viruses, but Seto is changing that. He is working to sequence 100 adenovirus genomes with BGI, a genome sequencing research center based in China; Massachusetts Eye and Ear Infirmary, which is affiliated with Harvard Medical School; and the University of Oklahoma Health Sciences Center. He also had a $1.6 million National Institutes of Health grant to study human adenoviruses.

“It’s important for these viruses to be characterized genomically, because if a new virus appears, we can find out if it is something we know or something new,” says U.S. Army Officer Major Morris S. Jones, a visiting scientist at the Naval Medical Center (San Diego) who’s working with Seto on the NIH grant as well as the BGI project. “These viruses can recombine and take on new characteristics.”

Those new characteristics may mean the virus is pathogenic and causes infections, Jones says.

Seto spearheaded the effort to study adenoviruses by looking at their entire genomic makeup using bioinformatic tools. “Don is the world’s expert in the field,” Jones says. “No one has done more to advance the genomic sequencing of adenoviruses.”

In the past, only a small part of the virus was used to define it, says James Chodosh, the David G. Cogan Professor of Ophthalmology in the field of  Cornea and External Disease at Harvard Medical School and a Seto colleague on the NIH grant and the BGI project. The virus could appear to be one virus but actually could be something quite different, he says. “The whole genome should be the basis for naming the virus,” Chodosh says.

Seto showed that with Ad55, the culprit behind the SARS-like outbreak in China, two different adenoviruses could combine to create a new one and make a lot of people sick, Chodosh says.

In the case of Ad55, the pathogen appeared to be a renal adenovirus that normally causes urinary tract infections, but that was only a small part of it. The majority of the virus was a highly contagious respiratory pathogen.

“It was almost like a Trojan horse virus,” Chodosh says. “This would never have come to light without Don’s work.”

Detailing the genomes of existing adenoviruses could help researchers predict what new viruses could appear next, Chodosh says. The sequencing work will give researchers a foundation to show them how a virus evolves. “We’re hoping we can fill in that database pretty quick,” he says.

A decade ago researchers had sequenced a mere handful of human adenoviruses. Now the number has risen to about 50, and a full 100 will be detailed by year’s end, Seto says.

“But all that means is we have 100 genomes,” he says. “It’s the computational analysis of the genomes that’s important. We need to correlate these with diseases and severity of diseases.”

Researchers also are studying animal adenoviruses for a good reason: HIV and Ebola both jumped from chimpanzees. SARS likely started with bats. At least one human adenovirus, now the most commonly isolated respiratory virus pathogen in the U.S. military, also jumped from chimpanzees and adapted to the new human host.

“One virus [Ad4] jumped from chimps to humans,” Seto says. “We showed that there are mutations that allowed it to become selected into the human population. When it first jumped in the ’40s and ’50s, it accounted for less than 1 percent of the human respiratory problems. Today it constitutes 99.9 percent of the ones found in the U.S. military. Somewhere between the ’50s and now it has evolved. It acquired some control switches that allow it to be more compatible with human lung cells.”

Seto’s work could make the “uncommon cold” better understood.

“I think we’re doing something that changes society,” Seto says. “It’s a different way of approaching viruses and diseases.”

This article originally appeared on the university’s News site.