Ubiquitous Reassortments in Influenza a Viruses

Abstract

The influenza A virus is a negative-stranded RNA virus composed of eight segmented RNA molecules, including polymerases (PB2, PB1, PA), hemagglutinin (HA), nucleoprotein (NP), neuraminidase (NA), matrix protein (MP), and nonstructure gene (NS). The influenza A viruses are notorious for rapid mutations, frequent reassortments, and possible recombinations. Among these evolutionary events, reassortments refer to exchanges of discrete RNA segments between co-infected influenza viruses, and they have facilitated the generation of pandemic and epidemic strains. Thus, identification of reassortments will be critical for pandemic and epidemic prevention and control. This paper presents a reassortment identification method based on distance measurement using complete composition vector (CCV) and segment clustering using a minimum spanning tree (MST) algorithm. By applying this method, we identified 34 potential reassortment clusters among 2,641 PB2 segments of influenza A viruses. Among the 83 serotypes tested, at least 56 (67.46%) exchanged their fragments with another serotype of influenza A viruses. These identified reassortments involve 1,957 H2N1 and 1,968 H3N2 influenza pandemic strains as well as H5N1 avian influenza virus isolates, which have generated the potential for a future pandemic threat. More frequent reassortments were found to occur in wild birds, especially migratory birds. This MST clustering program is written in Java and will be available upon request.

Possible Reason for Cross-Species and Cross-Subtype Reassortment in Polymerase Basic Protein 2 from Influenza A Virus

“…Serological test demonstrated that at least 56 subtypes (67.46%) exchanged their fragments with another subtype among 83 subtypes of influenza A viruses [5].…”

“…This question is important because the reassortment particularly facilitates the generation of pandemic and epidemic strains, which led to the pandemics in 1957 *Address correspondence to this author at the State Key Laboratory of Nonfood Biomass Enzyme Technology, National Engineering Research Center for Non-food Biorefinery, Guangxi Key Laboratory of Biorefinery, Guangxi Academy of Sciences, 98 Daling Road, Nanning, Guangxi, 530007, China; Tel: +86-771-2503930; Fax: +86-771-2503999; E-mail: hongguanglishibahao@yahoo.com and 1968 [1], the highly pathological H5N1 outbreaks [2][3][4], and the current H1N1 pandemic [5][6][7]. Among ten proteins from influenza A viruses, we have studied this question with respect to the hemagglutinin, neuraminidase, polymerase acidic protein, matrix protein 1 and 2 [8][9][10][11][12], which bioinformatically reveal the underlined mechanism for the crossspecies infection and cross-subtype reassortment.…”

Indications that Live Poultry Markets Are a Major Source of Human H5N1 Influenza Virus Infection in China

“…Seven different genotypes were detected among the 31 H5N1 isolates, including three not previously detected in humans ( Fig. 2 and 4; see Table S3 To identify potential avian virus gene precursors of each human isolate, we applied the CCV-MST method (1,22,23). One or more gene segments for most of the human H5N1 viruses isolated before 2007 had a corresponding gene segment in the public influenza database that was isolated from birds.…”

A systematic review of reported reassortant viral lineages of influenza A

“…Ideally, we would compare the output of such an analysis with the systematic review, to understand both detection and publication biases. However, to our knowledge, existing phylogenetic algorithms appear to have low sensitivity (since the number detected is much lower than found by our systematic review) [ 20 , 24 , 26 , 27 ], and the most robust algorithms would be difficult to apply to all available data, since they rely on assumptions of analysing random representative samples and are computationally expensive to apply to very large datasets [ 21 ].…”