It started with a single monkey coming down with pneumonia at the California National Primate Research Center in Davis. Within weeks, 19 monkeys were dead and three humans were sick. Now, a new report confirms that the Davis outbreak was the first known case of an adenovirus jumping from monkeys to humans. The upside: the virus may one day be harnessed as a tool for gene therapy.
Adenoviruses are relatively large DNA viruses—as opposed to many other viruses that replicate using RNA—that commonly cause colds and respiratory infections in humans. They're also responsible for a variety of illnesses in cattle, dogs, horses, pigs, and other animals, but scientists thought the viruses and their ailments couldn't jump between species.
Then, on 14 May 2009, a healthy adult male titi monkey—a small, reddish-brown species that calls much of South America home—came down with a cough at the Davis primate center and soon became lethargic and wouldn't eat. Staff members gave the animal intravenous fluids and antibiotics, but its condition worsened, and after 5 days staff members euthanized him. Four weeks later, another titi monkey came down with the same symptoms. Then another. And another. Within 2 months, 23 of the 65-strong population had become sick, and 19 eventually died. A team led by infectious diseases researcher Charles Chiu of the University of California, San Francisco, analyzed lung tissue samples from the dead monkeys and identified a never-before-seen adenovirus, which they named titi monkey adenovirus (TMAdV).
But where did the virus come from? It's unlikely it originated in the titi monkeys themselves, Chiu says: "Hosts that are that susceptible to a disease are not likely to be its originators." So the researchers asked whether any lab workers had been sick during that period. One person, who had had close daily contact with the monkeys, reported coming down with a fever, chills, a headache, a dry cough, and a burning sensation in her lungs—hallmarks of the kinds of respiratory infection commonly caused by adenoviruses. Two of her family members reported similar, though less severe, symptoms in subsequent weeks.
Neither the lab worker nor her family members sought medical attention, and all recovered within 4 weeks, after which it was too late for researchers to swab for traces of the adenoviruses directly. Instead, they examined the patients' blood for antibodies and compared them with those found in the infected monkeys. The lab worker and one of her family members showed a match, suggesting that the monkeys gave the virus to the lab worker or vice versa. But when the team tested a representative set of 81 blood samples from donors in the western United States, none had antibodies. That suggests humans weren't the source of the outbreak either.
After testing the other monkeys at the primate center, which houses hundreds of enclosures, the researchers found one healthy rhesus macaque with TMAdV antibodies. That suggests the disease might have arisen in the macaques and somehow passed to lab workers or the titi monkeys via shared medical equipment or some other contact between the two species, the researchers report today in PLoS Pathogens.
Although the virus didn't prove deadly, or even all that serious, to the humans it infected, the new findings suggest there may be more pathogens than previously thought with species-jumping potential. "Now we need to broaden our focus in looking at monkeys' and other animals' adenoviruses," Chiu says. "We've only touched the tip of the iceberg."
Michael Imperiale, a microbiologist at the University of Michigan, Ann Arbor, says TMAdV isn't necessarily a public health threat. He likens the virus to avian influenza, which humans can contract from birds but which is so poorly transmissible between people that it hasn't triggered an epidemic. "The question isn't just whether the virus can jump, but also whether it can widely spread," he says. "That hasn't been proven yet."
More troubling, Imperiale says, is that the primate center's lab workers appear to have ignored or skirted safety protocols. Chiu says that since the incident, the center has beefed up its oversight and emphasis on following protective measures.
TMAdV's rarity in humans could make it a potentially powerful tool as a viral vehicle for delivering gene therapy, Chiu adds. Researchers already use custom adenoviruses stitched with beneficial snippets of DNA to treat diseases; for instance, the cancer-fighting virus Gendicine introduces genes that code for the tumor-suppressing protein p53. The problem is that many people have antibodies to these viruses and their immune responses can make such treatments dangerous or even deadly. That problem likely wouldn't occur with an engineered version of TMAdV because nobody has antibodies to it. Chiu has a patent pending for using TMAdV as a gene-therapy vehicle.