epidemic ,

Why influenza B only infects humans

RUTGERS / U. TEXAS-AUSTIN (US) — Researchers say they now know why influenza B is limited to humans, a discovery that could lead to new drugs to fight seasonal flu epidemics.

The findings also help explain why influenza B cannot be as virulent as A strains that incorporate new genes from influenza viruses that infect other species. The devastating flu pandemic of 1918, the pandemics of 1968 and 1977, and the avian influenza that emerged in the middle of the last decade were caused by influenza A viruses.

Understanding features of influenza B virus that limit it to humans will help scientists better understand how influenza A strains are able to cross species.

Scientists determined the three-dimensional structure of a complex between an influenza B virus protein and one of its human protein targets, resulting in suppression of the cell’s natural defenses to the infection and paving the way for the virus to replicate efficiently.

Their findings are detailed in a paper published in the most recent issue of the Proceedings of the National Academy of Sciences.

“Our study shows the basis by which non-structural protein 1 of influenza B, or NS1B, binds to a human host protein, immobilizing it to prevent it from fighting the virus,” says Gaetano Montelione, a lead author and professor of biochemistry and molecular biology at Rutgers University.

That human protein, known as interferon-stimulated gene 15 protein or ISG15, is an essential part of the defense mechanism that human cells use to protect themselves from viral infections. Chemicals that block the binding of NS1B to ISG15 may have antiviral potential against influenza B virus.

The study, led by professors Montelione and Robert Krug at the University of Texas at Austin, also reveals why NS1B cannot bind ISG15 molecules in other species, such as dogs or mice. Only human and non-human primate ISG15 proteins have a unique molecular sequence in a small part of the protein that makes it possible to bind to the NS1B protein. So far, influenza B virus has been found only in humans.

“The three-dimensional structure of the NS1B-ISG15 complex, which we determined using X-ray crystallography, has given us a clear understanding of the molecular basis for this species specificity,” says Krug, professor and chair of molecular genetics and microbiology.

“Flu infections continue to be a major health problem, with more effective drugs critically needed to treat infected individuals and control potential pandemics,” says Aaron Shatkin, an eminent virologist at Rutgers. “This discovery opens new possibilities for achieving these very important goals.”

The work was supported by grants from the Protein Structure Initiative (PSI-Biology) Program of the National Institutes of Health and its National Institute of General Medical Sciences, the National Institute of Allergy and Infectious Disease, and the Howard Hughes Medical Institute.

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