Researchers have solved a fundamental mystery about smallpox that has puzzled scientists long after the natural disease was eradicated by vaccination: they know how it kills us. In a new research report appearing online in The FASEB Journal (http://www.fasebj.org), researchers describe how the virus cripples immune systems by attacking molecules made by our bodies to block viral replication. This discovery fills a major gap in the scientific understanding of pox diseases and lays the foundation for the development of antiviral treatments, should smallpox or related viruses re-emerge through accident, viral evolution, or terrorist action.
"These studies demonstrate the production of an interferon binding protein by variola virus and monkeypox virus, and point at this viral anti-interferon protein as a target to develop new therapeutics and protect people from smallpox and related viruses," said Antonio Alcami, Ph.D., a collaborator on the study from Madrid, Spain. "A better understanding of how variola virus, one of the most virulent viruses known to humans, evades host defenses will help up to understand the molecular mechanisms that cause disease in other viral infections."
Scientists produced the recombinant proteins from the variola virus and a similar virus that affects monkeys, causing monkeypox. The researchers then showed that cells infected with variola and monkeypox produced a protein that blocks a wide range of human interferons, which are molecules produced by our immune systems meant to stop viral replication.
"The re-emergence of pox viruses has potentially devastating consequences for people worldwide, as increasing numbers of people lack immunity to smallpox," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "Understanding exactly how pox viruses disrupt our immune systems can help us develop defenses against natural and terror-borne pox viruses."
Receive monthly highlights from The FASEB Journal by e-mail. Sign up at http://www.faseb.org/fasebjournalreaders.htm. The FASEB Journal (http://www.fasebj.org) is published by the Federation of the American Societies for Experimental Biology (FASEB). The journal has been recognized by the Special Libraries Association as one of the top 100 most influential biomedical journals of the past century and is the most cited biology journal worldwide according to the Institute for Scientific Information. FASEB comprises 22 nonprofit societies with more than 80,000 members, making it the largest coalition of biomedical research associations in the United States. FASEB advances health and welfare by promoting progress and education in biological and biomedical sciences through service to its member societies and collaborative advocacy.
Details: María del Mar Fernández de Marco, Alí Alejo, Paul Hudson, Inger K. Damon, and Antonio Alcami
The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon
FASEB J. doi:10.1096/fj.09-144733 http://www.fasebj.org/cgi/content/abstract/fj.09-144733v1
Journal
The FASEB Journal