Evolutionary and Transmission Dynamics of Reassortant H5N1 Influenza Virus in Indonesia

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Abstract
H5N1 highly pathogenic avian influenza (HPAI) viruses have seriously affected the Asian poultry industry since their recurrence in 2003. The viruses pose a threat of emergence of a global pandemic influenza through point mutation or reassortment leading to a strain that can effectively transmit among humans. In this study, we present phylogenetic evidences for the interlineage reassortment among H5N1 HPAI viruses isolated from humans, cats, and birds in Indonesia, and identify the potential genetic parents of the reassorted genome segments. Parsimony analyses of viral phylogeography suggest that the reassortant viruses may have originated from greater Jakarta and surroundings, and subsequently spread to other regions in the West Java province. In addition, Bayesian methods were used to elucidate the genetic diversity dynamics of the reassortant strain and one of its genetic parents, which revealed a more rapid initial growth of genetic diversity in the reassortant viruses relative to their genetic parent. These results demonstrate that interlineage exchange of genetic information may play a pivotal role in determining viral genetic diversity in a focal population. Moreover, our study also revealed significantly stronger diversifying selection on the M1 and PB2 genes in the lineages preceding and subsequent to the emergence of the reassortant viruses, respectively. We discuss how the corresponding mutations might drive the adaptation and onward transmission of the newly formed reassortant viruses. H5N1 highly pathogenic avian influenza (HPAI) virus emerged in China in 1996, and has spread beyond Asia since 2003. Following the first outbreak reported in Indonesian poultry farms in December 2003, the virus spilled over to 27 Indonesian provinces by June 2006, and became endemic in the country. In the following years, repeated sporadic human infections in Indonesia had been attributed to H5N1 HPAI viruses. Nonetheless, the viral evolution and transmission have not been fully understood. Here, we report phylogenetic evidence of a group of interlineage reassortant viruses isolated from human and cats in Java. Our comparative study of the reassortant viruses and one group of genetic parents found that although their rates of evolution were similar and both of their phylogenies were not geographically structured within mainland Java, the growths of genetic diversity were different. We also detected significant positive selection on the viral matrix and polymerase genes preceding and subsequent to the emergence of the reassortant viruses, which might correspond to viral adaptation. Based on our findings, we discuss the possibility of host switching in facilitating the emergence of the reassortant strain, and call for more extensive viral surveillances in the non-avian population in Indonesia.