Date Published: January 27, 2017
Publisher: Public Library of Science
Author(s): Xiang Yong Oong, Kim Tien Ng, Joon Ling Tan, Kok Gan Chan, Adeeba Kamarulzaman, Yoke Fun Chan, I-Ching Sam, Kok Keng Tee, Yury E Khudyakov.
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.
Influenza B is a member of the Orthomyxoviridae family and has an enveloped structure and segmented negative sense RNA genome , and is an important cause of respiratory infections in humans globally. The genome organization of influenza B virus is similar to that of influenza A virus, which consists of eight segments: polymerase basic-1 (PB1), polymerase basic-2 (PB2), polymerase acidic (PA), hemagglutinin (HA), nucleoprotein (NP), neuraminidase (NA), matrix protein (MP), and non-structural protein (NS) . First isolated in 1940 during an epidemic in the USA , influenza B viruses have been detected in different geographical regions worldwide . In the 1980s, two antigenically and genetically distinct lineages, B/Victoria/2/1987-like (Victoria lineage) and B/Yamagata/16/88-like (Yamagata lineage), have co-circulated in the human population, based on analysis of the HA gene .
There were 164/3,935 (children and adult outpatients) and 37/59 (hospitalized children) nasopharyngeal samples positive for HA and NA genes of influenza B viruses (S3 Table). Phylogenetic analysis of both genes identified similar circulation of Yamagata- and Victoria-lineage as well as Yam-2, Yam-3 and Vic-1 viruses between children and adult outpatients, and hospitalized children (S1 and S2 Figs, S3 Table). Furthermore, the analysis showed 36 B/Phuket/3073/2013-like viruses (28 in children and adult outpatients, 8 in hospitalized children) with intra-clade reassortment properties (HA-B/Wisconsin/01/2010-like/NA-B/Stockholm/12/2012-like) within Yam-3, one unique inter-clade reassortant (HA-Yam-2/NA-Yam-3) and one unique intra-clade reassortant within Vic-1 (HA-Vic-1B/NA-Vic-1A) (S1 and S2 Figs, S3 Table). To investigate the reassortment pattern of all eight gene segments of these reassortants from the lineage to the sub-clade level, four earliest detected B/Phuket/3073/2013-like intra-clade reassortants and the two unique reassortants sampled between 2012 and 2014 were chosen for further whole-genome analysis.