PNNL monkeypox research may apply to lung diseases

RICHLAND -- A new Richland-based study of an exotic infectious virus that has caused three recent outbreaks in the United States reveals clues to how the virus might damage lungs.

The findings also suggest possible new ways to treat lung diseases in humans, such as bronchitis and emphysema.

Not only does the infection from monkeypox virus increase production of proteins involved in inflammation, but it also decreases production of proteins that keep lung tissue intact and lubricated. The findings appear in an upcoming issue of Molecular & Cellular Proteomics.

"Going into this study, we thought monkeypox caused disease primarily by inducing inflammation in the lung, and that leads to pneumonia," said lead author Joseph Brown, a systems biologist at Pacific Northwest National Laboratory in Richland. "We were surprised to see how badly the virus wrecked the structural integrity of the lungs."

The study was paid for by the National Institute of Allergy and Infectious Diseases and the National Center for Research Resources, which are both part of the National Institutes of Health; the Department of Defense and Battelle.

In collaboration with the Oregon Health & Science University's Vaccine and Gene Therapy Institute in Beaverton, Brown and the PNNL team examined how the virus affected the collection of proteins found in lung fluid from macaque monkeys at OHSU. The monkeys were part of an ongoing study of monkeypox infection at OHSU's Oregon National Primate Research Center in Beaverton.

Monkeypox and smallpox are closely related viruses that cause contagious pustules in humans, although monkeypox is less dangerous. However, monkeypox is as bad for monkeys as smallpox is for people, making it a good model for human smallpox disease. The study helps researchers better understand both monkeypox and smallpox infection.

"If researchers confirm similar events in people, doctors might be able to give surfactants -- lubricating chemicals that aid in gas exchange -- to help the lung function. And the findings could lead to new areas of pulmonary studies in general -- bronchitis or emphysema, lung transplants, the flu," said PNNL co-author Josh Adkins.

Monkeypox infections in humans have been on the rise since smallpox was eradicated in the late 1970s. Up to 10 percent of those infected with monkeypox die of the disease.

Monkeypox can be caught from infected rodents, pets and monkeys. Although mainly found in Africa, the first documented infection in the United States occurred in 2003, likely from imported pet prairie dogs.

Researchers attribute the rise of monkeypox infections to the end of smallpox vaccinations, which provided protection against monkeypox due to the similar nature of the two viruses. The smallpox vaccine is based upon yet another pox virus called vaccinia, which usually doesn't cause symptoms in people.

A better understanding of how monkeypox causes disease could help doctors manage outbreaks, which likely will continue to occur. Findings about monkeypox infection also will provide insight into smallpox, which is considered a potential bioterrorism agent.

Battelle operates PNNL for the Department of Energy.