Their findings, which appeared online in the journal Eurosurveillance, provide clues to the virus’ origin, transmissibility, and potential sensitivity to existing influenza treatments. The research was funded through the Centers of Excellence for Influenza Research and Surveillance program of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and Japanese organizations.
“The H7N9 influenza virus is a new concern that the public health and scientific communities will continue to track closely, including watching for any genetic mutations that might enable the virus to become transmissible from person to person or to cause more severe disease,” said NIAID Director Anthony Fauci, M.D. “Having rapid access to the viral genetic information is essential to understanding how the virus is evolving and ultimately to developing a candidate vaccine, if warranted.”
Cases associated with the H7N9 influenza virus were first reported on March 31 by the Chinese Center for Disease Control and Prevention (Chinese CDC). As of April 17, 82 human infections with the novel strain had been confirmed, including 17 deaths. To date, the outbreak has been limited to eastern China, and there has been no evidence that the virus has been transmitted from human to human.
Influenza virus strains are classified and named based on two proteins present on the viral surface: hemagglutinin (HA), of which 17 subtypes are known, and neuraminidase (NA), of which 10 subtypes are known. H7N9 influenza features H7 HA and N9 NA surface proteins, a combination that had been previously seen only in birds. Between 1996 and 2012, related strains of H7N2, H7N3 and H7N7 influenza had been observed in humans in Europe and North America, but not in China.
Led by Masato Tashiro, M.D., Ph.D., of the National Institute of Infectious Diseases in Japan, and Yoshihiro Kawaoka, D.V.M., Ph.D., of the University of Wisconsin-Madison and the University of Tokyo, researchers analyzed sequenced genetic information of the H7N9 virus isolated from four of the earliest cases that resulted in death. The sequenced genetic information was provided by the Chinese CDC. Based on their analysis, the scientists concluded that the novel H7N9 strain acquired its surface protein genes from the H7N3 and H7N9 avian influenza strains, and its remaining genes from H9N2 influenza viruses that had recently circulated in poultry in China.
According to these researchers’ findings, the genetic information associated with the novel virus’ HA proteins suggests that the virus causes mild disease in birds but has mutated to more efficiently cause disease in mammals, including humans. All four of the HA sequences featured mutations that have been shown to improve the virus’ ability to bind to human cells, the first step in the infection process. All four viral sequences also contained a mutation associated with improved virus reproduction within human cells, which helps the infection spread throughout the body and cause disease. Additionally, all four of the NA sequences contain a mutation associated with more severe disease in mammals.
The researchers also used the genetic information to assess the potential susceptibility of the novel strain to common influenza treatments. Three of the four H7N9 viruses sequenced are likely to be treatable using NA inhibitors, a class of anti-influenza drugs that includes oseltamivir (Tamiflu) and zanamivir (Relenza). Analysis of all four sequences suggests that the novel strain will not be treatable with ion channel inhibitors, another major class of anti-influenza drugs.
Kageyama T et al. Genetic analysis of novel A(H7N9) influenza viruses isolated from patients in China, February to April 2013. Eurosurveillance 18(15) (2013).
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