Phylodynamics and Molecular Evolution of Influenza A Virus Nucleoprotein Genes in Taiwan between 1979 and 2009

Abstract

BackgroundMany studies concentrate on variation in the hemagglutinin glycoprotein (HA) because of its significance in host immune response, the evolution of this virus is even more complex when other genome segments are considered. Recently, it was found that cytotoxic T lymphocytes (CTL) play an important role in immunity against influenza and most CTL epitopes of human influenza viruses were remarkably conserved. The NP gene has evolved independently in human and avian hosts after 1918 flu pandemic and it has been assigned a putative role as a determinant of host range.Methods and FindingsPhylodynamic patterns of the genes encoding nucleoprotein (NP) of influenza A viruses isolated from 1979–2009 were analyzed by applying the Bayesian Markov Chain Monte Carlo framework to better understand the evolutionary mechanisms of these Taiwanese isolates. Phylogenetic analysis of the NP gene showed that all available H3 worldwide isolates collected so far were genetically similar and divided into two major clades after the year 2004. We compared the deduced amino acid sequences of the NP sequences from human, avian and swine hosts to investigate the emergence of potential adaptive mutations. Overall, selective pressure on the NP gene of human influenza A viruses appeared to be dominated by purifying selection with a mean dN/dS ratio of 0.105. Site-selection analysis of 488 codons, however, also revealed 3 positively selected sites in addition to 139 negatively selected ones.ConclusionsThe demographic history inferred by Bayesian skyline plot showed that the effective number of infections underwent a period of smooth and steady growth from 1998 to 2001, followed by a more recent rise in the rate of spread. Further understanding the correlates of interspecies transmission of influenza A virus genes from other host reservoirs to the human population may help to elucidate the mechanisms of variability among influenza A virus.

Surveillance of upper respiratory infections using a new multiplex PCR assay compared to conventional methods during the influenza season in Taiwan

“…The FilmArray system has the ability to perform high-order multiplex testing yet is simple to use and requires minimal hands-on time. Previous studies have shown the rapid evolution of Taiwanese influenza isolates in terms of antigenic and genetic diversity, which may result in epidemic strains that have the capacity to become the dominant strains worldwide (Chiu et al, 2014;Lin et al, 2011;Lin et al, 2007). Of note, the data from this study show that the FilmArray system was able to detect new genetic variants of the influenza A H3N2 virus even in the small number of samples tested.…”

“…With regard to seasonal influenza virus activity, previous studies have shown that it is possible to capture a significant proportion of influenza virus diversity in Taiwan, as well as the early emergence of new phylogenetic lineages and antigenic variants in neighboring countries, which are likely to be the progenitor epidemic strains in the following season (Chiu et al, 2014;Lin et al, 2011). In this study, the concurrent existence of European strains in the 3C.2a2 subclade was identified (Harvala et al, 2017), and this genetic observation showed that epidemic strains of the same serotype isolated in Taiwan were comparable to strains isolated elsewhere; however, the origin and effects of strains introduced from outside Taiwan could not be addressed in this study.…”

Genetic variations on 31 and 450 residues of influenza A nucleoprotein affect viral replication and translation

“…For example, R208A and R416A, which served as negative control in the mini-genome assay were shown to have very low polymerase activity and failed to rescue as reverse genetics viruses. There have been several evolutionary analyses focused on the NP gene segment in recent years [24,25] and by phylogenetic analysis, separate clades from human, avian or swine origins can be identified. Some positive selection sites on NP were found, one of which was residue 450 [16].…”

PhyloTempo: A Set of R Scripts for Assessing and Visualizing Temporal Clustering in Genealogies Inferred from Serially Sampled Viral Sequences

“…In particular, the shape of a phylogenetic tree often reflects the characteristics and the interactions among evolutionary and ecological processes. For example, phylogenies of viruses under continuous positive selection, such as inter-host influenza or intrahost human immunodeficiency virus (HIV), usually exhibit a marked staircase-like topology 3,4. Pathogens under weak or absent positive selection show a more balanced tree shape, as it happens within the measles serotypes 5.…”