Abstract
BackgroundInfluenza neuraminidase (NA) is an important surface glycoprotein and plays a vital role in viral replication and drug development. The NA is found in influenza A and B viruses, with nine subtypes classified in influenza A. The complete knowledge of influenza NA evolutionary history and phylodynamics, although critical for the prevention and control of influenza epidemics and pandemics, remains lacking.Methodology/Principal findingsEvolutionary and phylogenetic analyses of influenza NA sequences using Maximum Likelihood and Bayesian MCMC methods demonstrated that the divergence of influenza viruses into types A and B occurred earlier than the divergence of influenza A NA subtypes. Twenty-three lineages were identified within influenza A, two lineages were classified within influenza B, and most lineages were specific to host, subtype or geographical location. Interestingly, evolutionary rates vary not only among lineages but also among branches within lineages. The estimated tMRCAs of influenza lineages suggest that the viruses of different lineages emerge several months or even years before their initial detection. The d N /d S ratios ranged from 0.062 to 0.313 for influenza A lineages, and 0.257 to 0.259 for influenza B lineages. Structural analyses revealed that all positively selected sites are at the surface of the NA protein, with a number of sites found to be important for host antibody and drug binding.Conclusions/SignificanceThe divergence into influenza type A and B from a putative ancestral NA was followed by the divergence of type A into nine NA subtypes, of which 23 lineages subsequently diverged. This study provides a better understanding of influenza NA lineages and their evolutionary dynamics, which may facilitate early detection of newly emerging influenza viruses and thus improve influenza surveillance.
Highlights
Influenza virus belongs to the viral family Orthomyxoviridae and has a segmented negative-sense RNA genome in an enveloped virion [1]
This study provides a better understanding of influenza NA lineages and their evolutionary dynamics, which may facilitate early detection of newly emerging influenza viruses and improve influenza surveillance
The Maximum Likelihood (ML) and Markov Chain Monte Carlo (MCMC) Bayesian analyses demonstrate that the influenza NA gene diverged first into A and B (Group I and Group II), followed by the division of influenza A subtypes (Figure 1, File S1)
Summary
Influenza virus belongs to the viral family Orthomyxoviridae and has a segmented negative-sense RNA genome in an enveloped virion [1]. Like most RNA viruses, the influenza virus has low fidelity RNA synthesis, which results in a high mutation rate - around one mutation per genome per replication [6], several orders of magnitude higher than those in most DNA-based organisms [7] Evolutionary forces such as natural selection acting upon rapidly mutating viral populations could shape the genetic structure of influenza viruses in different hosts, geographic regions and periods of time [8,9]. Rapid evolution could partially facilitate the ability of influenza viruses to cross host species barriers and successfully emerge in new hosts with often important public health and/or veterinary health implications One such example is the Eurasian avian-like H1N1 swine virus, which was first detected in pigs in Belgium in 1979, with all of the eight segments found to be derived from a Eurasian avian H1N1 virus, presumably following adaptive mutation [10]. The complete knowledge of influenza NA evolutionary history and phylodynamics, critical for the prevention and control of influenza epidemics and pandemics, remains lacking
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