Whole-Genome Phylogenetic Analysis of Influenza B/Phuket/3073/2013-Like Viruses and Unique Reassortants Detected in Malaysia between 2012 and 2014

Abstract

Reassortment of genetic segments between and within influenza B lineages (Victoria and Yamagata) has been shown to generate novel reassortants with unique genetic characteristics. Based on hemagglutinin (HA) and neuraminidase (NA) genes, recent surveillance study has identified reassortment properties in B/Phuket/3073/2013-like virus, which is currently used in the WHO-recommended influenza vaccine. To understand the potential reassortment patterns for all gene segments, four B/Phuket/3073/2013-like viruses and two unique reassortants (one each from Yamagata and Victoria) detected in Malaysia from 2012–2014 were subjected to whole-genome sequencing. Each gene was phylogenetically classified into lineages, clades and sub-clades. Three B/Phuket/3073/2013-like viruses from Yamagata lineage were found to be intra-clade reassortants, possessing PA and NA genes derived from Stockholm/12-like sub-clade, while the remaining genes from Wisconsin/01-like sub-clade (both sub-clades were within Yamagata Clade 3/Yam-3). However, the other B/Phuket/3073/2013-like virus had NS gene that derived from Stockholm/12-like sub-clade instead of Wisconsin/01-like sub-clade. One inter-clade reassortant had Yamagata Clade 2/Yam-2-derived HA and NP, and its remaining genes were Yam-3-derived. Within Victoria Clade 1/Vic-1 in Victoria lineage, one virus had intra-clade reassortment properties: HA and PB2 from Vic-1B sub-clade, MP and NS from a unique sub-clade “Vic-1C”, and the remaining genes from Vic-1A sub-clade. Although random reassortment event may generate unique reassortants, detailed phylogenetic classification of gene segments showed possible genetic linkage between PA and NA genes in B/Phuket/3073/2013-like viruses, which requires further investigation. Understanding on reassortment patterns in influenza B evolution may contribute to future vaccine design.

Molecular evolution of influenza B virus during 2011–2017 in Chaoyang, Beijing, suggesting the free influenza vaccine policy

“…Interestingly, we observed Yamagata/Victoria inter-lineage reassortment with HA of Yamagata-lineage and NA of Victoria-lineage, which was dominant in 2013–2014 seasons. The reassortment was reported in other researches and caused Yamagata-lineage to be dominated strain 31 . In conclusion, one or multiple mutation of four epitopes and subtypes reassortment may cause preponderant strain.…”

Genetic characterization of influenza B virus in Cameroon and high frequency of reassortant strains

“…The antigenic site that presented with the highest number of substitutions among influenza B strains from Cameroon was the 120‐loop region that has been shown to be subject to accumulation of amino acid changes due to its structural flexibility . Diversity in this 120‐loop has been noted as well from in influenza B strains from other regions around the world . Victoria lineages showed a higher diversity in the epitope regions as compared with Yamagata lineages suggesting a slower evolutionary rate of the latter.…”

“…The segments of influenza B virus have been classified into several clades and groups; however, the ability for influenza to reassort renders viral classification difficult . Genome characterization of the HA gene revealed that Cameroonian strains of the Victoria lineages clustered into two distinct groups of the Victoria clade 1A, different from the vaccine strain B/Brisbane/60/2008, while Yamagata lineages drifted from Yamagata clade 2 in 2014 to Yamagata clade 3 in the following years.…”

“…Similar results were reported in other studies where frequent HA and NA reassortments were noted though with lower incidence. Past findings show that reassortment plays a primordial role in the evolution of influenza B virus due to the presence of frequent exchange of portions of genes within several segments of multiple viral lineages . Full genome sequencing of Cameroonian strains is essential to understand the extent of reassortment within different genes and its role in influenza B virus evolution.…”

Analysis of influenza B virus lineages and the HA1 domain of its hemagglutinin gene in Guangzhou, southern China, during 2016

“…Since 1983, influenza B viruses have been classified into two distinct lineages according to their antigenicity and gene sequences: B/Victoria/2/87-like (Victoria) and B/Yamagata/16/88-like (Yamagata) [ 1 , 2 ]. Gene segment reassortment between and within these lineages has contributed to the genetic diversity of this virus [ 3 ].…”