Editors' ChoiceInfluenza

From Bird to Mammal

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Science Translational Medicine  22 May 2013:
Vol. 5, Issue 186, pp. 186ec86
DOI: 10.1126/scitranslmed.3006553

The recent emergence of a novel avian influenza A (H7N9) virus in China renews public health concerns about another lethal avian influenza A (H5N1) virus, which usually causes human infections through contact with infected birds. If by exchanging genes with other strains of influenza, one of the avian influenza viruses could gain the ability to be easily and sustainably transmitted among humans, it would set the stage for a highly lethal pandemic.

Zhang and colleagues investigated whether reassortments of genes between the avian H5N1 virus and the highly transmissible (but less deadly) pandemic 2009 H1N1 influenza A strain could result in a hybrid virus that causes deadly infection and can be transmitted in respiratory droplets among mammals. They created 127 hybrid viruses that retained the hemagglutinin (HA) gene of H5N1. This gene encodes the protein that binds to host cells and confers specificity for birds. This avian HA gene was grouped with different combinations of the other seven genes from H1N1. The authors found 89 viruses that caused comparable or more severe disease than H5N1 in mice—a correlate of human disease severity. They also determined whether infected guinea pigs could transmit hybrid viruses in respiratory droplets by placing healthy animals in cages adjacent to those of infected guinea pigs, then testing for virus in nasal washings and antibodies in the blood. Eight of 21 hybrid viruses tested were able to pass from infected to neighboring guinea pigs, including four viruses that transmitted faster than H1N1; none of the guinea pigs died.

This and similar studies have been controversial because of concerns for release of these potentially deadly viruses from the laboratory, resulting in a year-long moratorium on such studies. Zhang et al. report that their study was conducted before the moratorium, in an enhanced animal biosafety level 3 facility approved for the handling of such viruses. Nonetheless, this study confirms that reassortments between highly pathogenic and highly transmissible influenza viruses, even without changes in the HA gene, can result in hybrid viruses that are both pathogenic and easily transmissible. This study raises concern that such reassortments could happen in nature. It also provides clues as to which gene combinations may be responsible for conferring transmissibility, which could help scientists better identify these viruses and interrupt transmission.

Y. Zhang et al., H5N1 hybrid viruses bearing 2009/H1N1 virus genes transmit in guinea pigs by respiratory droplet. Science, 2 May 2013 (Doi:10.1126/science.1229455). [Abstract]

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