Atypical influenza A(H1N1)pdm09 strains caused an influenza virus outbreak in Saudi Arabia during the 2009–2011 pandemic season

Background: The triple assortment influenza A(H1N1) virus emerged in spring 2009 and disseminated worldwide, including Saudi Arabia. This study was carried out to characterize Saudi influenza isolates in relation to the global strains and to evaluate the potential role of mutated residues in transmission, adaptation, and the pathogenicity of the virus. Methods: Nasopharyngeal samples (n = 6492) collected between September 2009 to March 2011 from patients with influenza-like illness were screened by PCR for influenza A(H1N1). Phylogenetic and Molecular evolutionary analysis were carried out to place the Saudi strains in relation to the global strains followed by Mutation analysis of surface and internal proteins. Results: Concatenated whole-genome phylogenetic analysis along with hemagglutinin (HA) signature changes, that is, Aspartic Acid (D) at position 187, P83S, S203T, and R223Q confirmed that the Saudi strains belong to the antigenic category of A/California/07/2009. However, phylogenetic analysis revealed unusual strains of A(H1N1) circulating in Saudi Arabia, not belonging to any of known clades, appearing in five distinct groups well supported by group-specific mutations and novel mutation complexes. These cases had characteristic inter- and intragroup substitution patterns while few of their closest matches showed up as sporadic cases the world over. Specific mutation patterns were detected within the functional domains of internal proteins PB2, PB1, PA, NP, NS1, and M2 having a putative role in viral fitness and virulence. Bayesian coalescent MCMC analysis revealed that Saudi strains belonged to cluster 2 of A(H1N1)pdm09 and spread a month later as compared to other strains of this cluster. Conclusion: Influenza outbreak in Saudi Arabia during 2009–2011 was caused by atypical strains of influenza A(H1N1)pdm09, probably introduced in this community on multiple occasions. To understand the antigenic significance of these novel point mutations and mutation complexes require functional studies, which will be crucial for risk assessment of emergent strains and defining infection control measures.