Phylogeography and evolutionary history of reassortant H9N2 viruses with potential human health implications

Abstract

Avian influenza viruses of the H9N2 subtype have seriously affected the poultry industry of the Far and Middle East since the mid-1990s and are considered one of the most likely candidates to cause a new influenza pandemic in humans. To understand the genesis and epidemiology of these viruses, we investigated the spatial and evolutionary dynamics of complete genome sequences of H9N2 viruses circulating in nine Middle Eastern and Central Asian countries from 1998 to 2010. We identified four distinct and cocirculating groups (A, B, C, and D), each of which has undergone widespread inter- and intrasubtype reassortments, leading to the generation of viruses with unknown biological properties. Our analysis also suggested that eastern Asia served as the major source for H9N2 gene segments in the Middle East and Central Asia and that in this geographic region within-country evolution played a more important role in shaping viral genetic diversity than migration between countries. The genetic variability identified among the H9N2 viruses was associated with specific amino acid substitutions that are believed to result in increased transmissibility in mammals, as well as resistance to antiviral drugs. Our study highlights the need to constantly monitor the evolution of H9N2 viruses in poultry to better understand the potential risk to human health posed by these viruses.

Fig. 1.

Influenza virus subtypes included in the phylogenetic analysis of internal gene segments.

Fig. 2.

ML phylogenetic tree for the HA gene segment of H9N2 avian influenza viruses from the Middle East and Asia. Sequences of H9N2 viruses analyzed in this study are highlighted with different colors, according to the countries of origin, as follows: purple for Iran, green for Israel, red for Saudi Arabia, gray for the UAE, yellow for Afghanistan, orange for Pakistan, blue for Jordan, and light blue for Iraq. Genetic groups are colored as follows: group A is blue, group B is green, group C is red, and group D is yellow. The numbers at the nodes represent bootstrap values.

Fig. 3.

ML phylogenetic tree for the NA gene segment of H9N2 avian influenza viruses from the Middle East and Asia. The color scheme is the same as that used in Fig. 2.