Evolution and rapid spread of a reassortant A(H3N2) virus that predominated the 2017-2018 influenza season

Abstract

The 2017-2018 North American influenza season caused more hospitalizations and deaths than any year since the 2009 H1N1 pandemic. The majority of recorded influenza infections were caused by A(H3N2) viruses, with most of the virus's North American diversity falling into the A2 clade. Within A2, we observe a subclade which we call A2/re that rose to comprise almost 70% of A(H3N2) viruses circulating in North America by early 2018. Unlike most fast-growing clades, however, A2/re contains no amino acid substitutions in the hemagglutinin (HA) segment. Moreover, HI assays did not suggest substantial antigenic differences between A2/re viruses and viruses sampled during the 2016-2017 season. Rather, we observe that the A2/re clade was the result of a reassortment event that occurred in late 2016 or early 2017 and involved the combination of the HA and PB1 segments of an A2 virus with neuraminidase (NA) and other segments a virus from the clade A1b. The success of this clade shows the need for antigenic analysis that targets NA in addition to HA. Our results illustrate the potential for non-HA drivers of viral success and necessitate the need for more thorough tracking of full viral genomes to better understand the dynamics of influenza epidemics.

Integrating genotypes and phenotypes improves long-term forecasts of seasonal influenza A/H3N2 evolution

“…LBI performed especially poorly in the last two test timepoints of April and October 2018 ( Figure 8 ). These timepoints correspond to the dominance and sudden decline of a reassortant clade named A2/re ( Potter et al, 2019 ). By April 2018, the A2/re clade had risen to a global frequency over 50% from less than 15% the previous year, despite an absence of antigenic drift.…”

Immuno-informatics study identifies conserved T cell epitopes in non-structural proteins of Bluetongue virus serotypes: formulation of a computationally optimized next-generation broad-spectrum multi-epitope vaccine

“…Mouse models are increasingly becoming valuable for testing T cell-mediated immunity of vaccines against BT ( 17 , 38 , 106 ). Particularly, the C57BL/6 background mouse model has been well established for studying the pathogenesis and vaccine development for BTV ( 4 , 5 , 7 , 83 ). Therefore, in the present study, we used the C57BL/6 MHC class I H2-D b and H2-K b , and class II H2-IA b haplotypes for predicting CD8+ and CD4+ T cell epitopes in NS1, NS2 and NS3 proteins of BTV.…”

Low Influenza Vaccine Effectiveness Against A(H3N2)-Associated Hospitalizations in 2016–2017 and 2017–2018 of the Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN)

“…For hemagglutinin, the cross-reactivity is not surprising; A/Singapore (H3N2) and A/Hong Kong (H3N2) are antigenically similar with both expected to have the same egg-related mutation demonstrated to drive antibody response. However, neuraminidase cross-reactivity between the 2 strains was unexpected given that A(H3N2) viruses predominant in 2017-2018 were reassortants with hemagglutinin and neuraminidase segments from separate 3c.2A subclades [39]. NAI titers did not protect against infection, a finding that may be related to issues with the quality of the antibody [40] or with continued antigenic change of the neuraminidase [39].…”

“…However, neuraminidase cross-reactivity between the 2 strains was unexpected given that A(H3N2) viruses predominant in 2017-2018 were reassortants with hemagglutinin and neuraminidase segments from separate 3c.2A subclades [39]. NAI titers did not protect against infection, a finding that may be related to issues with the quality of the antibody [40] or with continued antigenic change of the neuraminidase [39]. Increased antigenic characterization of the neuraminidase of circulating viruses is potentially needed to understand future patterns of circulation and severity, and to aid in vaccine strain selection.…”