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

Author:

Blumenkrantz Deena R1ORCID,Mehoke Thomas2ORCID,Shaw-Saliba Kathryn13,Powell Harrison1,Wohlgemuth Nicholas1ORCID,Liu Hsuan1,Macias Elizabeth4,Evans Jared2,Lewis Mitra5,Medina Rebecca5,Hardick Justin5,Sauer Lauren M5,Dugas Andrea5,DuVal Anna3,Lane Andrew P6ORCID,Gaydos Charlotte35,Rothman Richard35,Thielen Peter2ORCID,Pekosz Andrew1ORCID

Affiliation:

1. W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health,Laurel, MD, USA

2. Research and Exploratory Development Department, Johns Hopkins Applied Physics Laboratory, Laurel, MD, USA

3. Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA

4. Epidemiology Laboratory Service, United States Air Force School of Aerospace Medicine, Wright-Patterson Air Force Base, OH, USA

5. Department of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

6. Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Abstract

Abstract The 2014–15 influenza season saw the emergence of an H3N2 antigenic drift variant that formed the 3C.2a HA clade. Whole viral genomes were sequenced from nasopharyngeal swabs of ninety-four patients with confirmed influenza A virus infection and primary human nasal epithelial cell cultures used to efficiently isolate H3N2 viruses. The isolates were classified by HA clade and the presence of a new set of co-selected mutations in NA (a glycosylation site, NAg+) and PB1-F2 (H75P). The NA and PB1-F2 mutations were present in a subset of clade 3C.2a viruses (NAg+F2P), which dominated during the subsequent influenza seasons. In human nasal epithelial cell cultures, a virus with the novel NAg+F2P genotype replicated less well compared with a virus with the parental genotype. Retrospective analyses of clinical data showed that NAg+F2P genotype viruses were associated with increased cough and shortness of breath in infected patients.

Publisher

Oxford University Press (OUP)

Subject

Virology,Microbiology

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