Pandemic (H1N1) 2009 virus revisited: an evolutionary retrospective

Abstract

The pandemic (H1N1) 2009 virus is unique in many aspects, especially in its genetics and evolution. In this paper, we examine the molecular mechanisms underlying the evolution of this novel virus through a comprehensive bioinformatics analysis, and present results in the context of a review of the literature. The pandemic virus was found to arise from a reassortment of two swine viruses, each of which ultimately arose from interspecies transmission. It experienced fast evolutionary rates and strong selection pressures, diverging into two different clusters at the early pandemic stage. Cluster I became extinct at the end of 2009 whereas Cluster II continued to circulate at much lower rates in 2010. Therefore, on August 10 of 2010 the WHO declared the end of the pandemic. Important mutations associated with host specificity, virulence, and drug resistance were detected in the pandemic virus, indicating effective transmission and increased severity in humans. Much has been learned about the evolutionary dynamics of this pandemic virus; however, it is still impossible to predict when the next pandemic will occur and which virus will be responsible. Improved surveillance at different levels (both national and international) and in different hosts (especially in swine) appears to be crucial for early detection and prevention of future influenza pandemics.

Figure 1

Number of confirmed human cases of pandemic (H1N1) 2009 reported to WHO and the number of sequences submitted to NCBI during the pandemic period.

Figure 2

Multiple reassortments contributed to the pandemic (H1N1) 2009 virus.

Figure 3

Maximum likelihood tree using concatenated genome sequences of all pandemic (H1N1) 2009 viral strains available in NCBI. Viral strains isolated from April-June, 2009 are colored in blue; July- September, 2009 in red; October-December 2009 in green; January-March, 2010 in purple.

Figure 4

Structural alignment of the HA segment of three different influenza A H1N1 viruses showing a mutation at position D222G. The different chains: red, grey, and yellow, show the different subunits of the HA trimer. Antigenic regions of HA are also color coded (Ca, Orange; Cb, Blue; Sa, Pink; Sb, Cyan).The H1N1 HA segments of the viruses used for this alignment are A/Darwin/2001/2009 (3M6S), A/Swine/Iowa/15/1930(1RUY), and A/SouthCarolina/1/1918(1RUZ). The smaller region at the lower right corner zooms in on the Ca region to show the D222G mutation.