Identification of H3N2 NA and PB1-F2 genetic variants and their association with disease symptoms in the 2014-15 influenza season

Autor: Deena R. Blumenkrantz, Andrew P. Lane, Kathryn Shaw-Saliba, Jared D. Evans, Elizabeth Macias, Richard E. Rothman, Anna DuVal, Hsuan Liu, Justin Hardick, Peter Thielen, Nicholas Wohlgemuth, Lauren Sauer, Mitra Lewis, Charlotte A. Gaydos, Harrison Powell, Andrew Pekosz, Rebecca Medina, Thomas Mehoke, Andrea Dugas
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Virus Evolution
DOI: 10.1101/2020.02.20.956979
Popis: The 2014-15 influenza season saw the emergence of an antigenic drift variant of H3N2 which formed the 3C.2a HA clade. Nasopharyngeal swabs from patients with confirmed influenza A virus infection were used for whole viral genome sequencing to make HA clade calls and identify mutations in the NA (a new glycosylation site, NAg+) and PB1-F2 (H75P mutation). The mutations in NA and PB1-F2 that were present in a subset of clade 3C.2a viruses (NAg+F2P) which came to dominate in the subsequent influenza season. The NAg+F2P genotype viruses were associated with increased wheezing and shortness of breath in infected patients. The use of primary human nasal epithelial cell cultures allowed for more efficient isolation of H3N2 viruses and identified replication differences between H3N2 genotypes. The use of sequencing of clinical samples combined with in vitro analysis of virus replication provided a unique system for identifying and characterizing novel variants of influenza A virus. Conclusions In 2014-15, H3N2 antigenic drift variants of HA clade 3C.2a were the dominant influenza virus strain identified in the Johns Hopkins Center of Excellence in Influenza Research and Surveillance (JH CEIRS) network. H3N2 antigenic drift variants (HA clades) and additional mutations in other gene segments were determined by direct sequencing of human nasal swabs or washes. Virus isolation on hNECs was more efficient than isolation on MDCK cells. An NA mutation introducing a putative glycosylation site co-segregated with a PB1-F2 mutation (H75P). Viruses with the NAgly+ H75P genotype were associated with increased reporting of some clinical symptoms.
Databáze: OpenAIRE