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UCSF Researchers Use ViroChip to ID Virus that Devastated Monkey Colony, Infected Humans


By Justin Petrone

Researchers at the University of California in San Francisco have used array technology to identify an adenovirus that spread through a California monkey colony in 2009 and also infected a human researcher and two family members.

The finding is the first known example of an adenovirus jumping from one species to another and remaining contagious after the jump.

These are the "most significant findings" of the study, carried out by the UCSF Viral Diagnostics and Discovery Center, according to its director, Charles Chiu. Chiu told BioArray News that the new adenovirus, referred to as the titi monkey adenovirus, is a "highly divergent and a novel species," and is interesting to researchers because of the apparent cross-species transmission.

"Now adenoviruses can be added to the list of pathogens that have the ability to cross species," said Chiu, who is also an assistant professor of laboratory medicine and infectious diseases at UCSF. "It's been hinted at before, but this study is the first to document these viruses crossing the species barrier in real time."

The findings appear in the July 14 issue of PLoS Pathogens.

The virus at the center of the research infected more than a third of the titi monkeys in the California National Primate Research Center at the University of California Davis in late 2009. Titi monkeys are New World monkeys that live in South America, from Colombia to Brazil, Peru and north Paraguay.

According to the paper, the virus caused an upper respiratory illness that progressed to pneumonia and eventually killed 19 of the 23 monkeys that became sick, including healthy young adult monkeys.

A researcher who was taking care of the sick monkeys also developed an upper respiratory infection, with fever, chills and a cough that lasted four weeks, as did two members of the researcher's family who had no contact with the monkey colony. All three recovered fully without medical treatment.

Chiu said that CNPRC Director Nick Lerche contacted him in an attempt to elucidate the cause of the outbreak and prevent its spread to other animals. The UCSF researchers, who included paper lead author Eunice Chen, used the center's ViroChip to study sera from the infected monkeys.

Chiu said the team used the latest version of the ViroChip, which was updated in December 2008 to include 60,000 probes. The array, manufactured by Agilent Technologies, covers about 1,800 viruses and was originally developed by Chiu's fellow UCSF researchers Joe DeRisi and Don Ganem in 2003 in response to the SARS virus outbreak.

Because the researcher's illness was not reported for several months, the virus could no longer be detected directly. Chiu worked with the California Department of Public Health to conduct antibody testing on the monkeys, the researcher, and two of the researcher's family members who also reported having been sick.

The UCSF team found that the new virus belonged to the adenovirus family, but was unlike any adenovirus ever reported to infect humans or monkeys. According to the paper, it shares only 56 percent of its DNA with its closest viral relative. Because the virus is so unusual, the authors suggested that it may have originated from a third, unidentified species.

"Given the unusually high fatality rate in the titi monkeys, they are not likely to be the native host species for this virus," Chiu said. "We still don’t know what species is the natural host."

After testing other monkeys at the CNPRC, the UCSF researchers found one healthy rhesus monkey with antibodies to the virus. Rhesus monkeys are native to South, Central, and Southeast Asia. Chiu said the finding could indicate that the virus originated in Old World monkeys, then spread to the New World colony that lacked antibodies against it.

Still, the direction in which the virus spread remains unconfirmed. "We haven't actually formally excluded human-to-monkey [transmission] or [whether it arose] from other animal reservoirs yet, but these studies are ongoing," said Chiu.

UCSF is now surveying humans and monkeys in the US, Brazil, and Africa to determine whether the virus is common in wild populations of Old World or New World monkeys, and whether it has crossed species in those settings to humans who live nearby.

According to Chiu, the researchers will conduct "more extensive seroepidemiology to identify the host reservoir" of the virus and "assess its danger to humans. The researchers are also looking at all primates at the CNPRC as well as in affiliated zoos and will conduct animal inoculation experiments to demonstrate pathogenicity and identify changes in the genome upon adaptation to culture.

UCSF has filed a patent application related to the new adenovirus, according to a statement from the university.

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Chiu is overseeing several other projects. He and his fellow researchers were awarded an $888,000 grant from the National Institutes of Health last year to develop a rapid, pan-viral microarray diagnostic for category A-C biodefense pathogens.

Chiu's team is working to co-develop the assay with Frederick, Md.-based Akonni Biosystems, while the UCSF Clinical Microbiology Laboratory under the direction of Steve Miller and Jean Patterson's lab at the Southwest Foundation for Biomedical Research in San Antonio, Texas, will validate it

He discussed the project with BioArray News last year (BAN 9/7/2010).

This week, Chiu said that the portable pathogen-detection project is going well.

"We have successfully ported Virochip probes and validated the assay for some targeted diarrheal [and] respiratory viral pathogens [such as] influenza, norovirus, [and] poliovirus to this format, and have the assay down to 4 hours" versus between 12 and 24 hours for the original Virochip.

Chiu said his team has also able to test the efficacy of the assay for detection of Marburg, Ebola Zaire, and Ebola Sudan viruses. "I anticipate that we should have a manuscript submitted on the topic within a few months," he said.

Have topics you'd like to see covered in BioArray News? Contact the editor at jpetrone [at] genomeweb [.] com

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