A new study published in the Proceedings of the National Academy of Science (PNAS) indicates that a virulent hybrid of the H5N1 avian influenza and human seasonal flu viruses could occur if just one gene is swapped between the two viruses.
The spread of avian H5N1 influenza viruses around the globe has become a worldwide public health concern. To evaluate the pathogenic potential of reassortant viruses between currently co-circulating avian H5N1 and human H3N2 influenza viruses, researchers generated all the 254 combinations of reassortant viruses between A/chicken/South Kalimantan/UT6028/06 (SK06, H5N1) and A/Tokyo/Ut-Sk-1/07 (Tok07, H3N2) influenza viruses by reverse genetics. They found that the presence of Tok07 PB2 protein in the ribonucleoprotein (RNP) complex allowed efficient viral RNA transcription in a minigenome assay and that RNP activity played an essential role in the viability and replicative ability of the reassortant viruses.
When the pathogenicity of 75 reassortant H5 viruses was tested in mice, 22 were more pathogenic than the parental SK06 virus, and three were extremely virulent. The researchers report that all 22 of these viruses obtained their PB2 segment from Tok07 virus. Further analysis showed that Tok07 PB1 alone lacked the ability to enhance the pathogenicity of the reassortant viruses but could do so by cooperating with Tok07 PB2.
The researchers say their data demonstrate that reassortment between an avian H5N1 virus with low pathogenicity in mice and a human virus could result in highly pathogenic viruses and that the human virus PB2 segment functions in the background of an avian H5N1 virus, enhancing its virulence. They say their findings highlight the importance of surveillance programs to monitor the emergence of human H5 reassortant viruses, especially those containing a PB2 segment of human origin.
Reference: Lia C, et al. Reassortment between avian H5N1 and human H3N2 influenza viruses creates hybrid viruses with substantial virulence. PNAS. Feb. 22, 2010.