J Med Virol. 2019 Sep 9. doi: 10.1002/jmv.25589. [Epub ahead of print]
Genetic and antigenic characteristics of a human influenza C virus clinical isolate.

Liu R1,2,3, Sheng Z4, Lin T5, Sreenivasan C1,2,3, Gao R1,2,3, Thomas M1,2, Druce J6, Hause BM7, Kaushik RS1,2, Li F1,2,3, Wang D1,3.
Author information

1 Department of Biology and Microbiology, South Dakota State University, Brookings, SD, USA. 2 Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD, USA. 3 BioSNTR, Brookings, SD, USA. 4 Department of Biochemistry and Molecular Biophysics, Department of Systems Biology, Columbia University, New York, NY, USA. 5 Department of Chemistry and Biochemistry, South Dakota State University, Brookings, SD, USA. 6 Victorian Infectious Diseases Reference Laboratory, Melbourne, Victoria, Australia. 7 Cambridge Technologies Inc., Worthington, USA.


Unlike influenza A and B viruses that infect humans and cause severe diseases in seasonal epidemics, influenza C virus (ICV) is a ubiquitous childhood pathogen typically causing mild respiratory symptoms. ICV infections are rarely diagnosed and less research has been performed on it despite the virus being capable of causing severe disease in infants. Here we report on the isolation of a human ICV from a child with acute respiratory disease, provisionally designated C/Victoria/2/2012 (C/Vic). The full-length genome sequence and phylogenetic analysis revealed that the hemagglutinin-esterase-fusion (HEF) gene of C/Vic was derived from C/Sao Paulo lineage, while its PB2 and P3 genes evolved separately from all characterized historical ICV isolates. Furthermore, antigenic analysis using the HI assay found that 1947 C/Taylor virus (C/Taylor lineage) was antigenically more divergent from1966 C/Johannesburg (C/Aichi lineage) than from 2012 C/Vic. Structure modeling of the HEF protein identified two mutations in the 170-loop of the HEF protein around the receptor binding pocket as a possible antigenic determinant responsible for the discrepant HI results. Taken together, results of our studies reveal novel insights into the genetic and antigenic evolution of ICV and provide a framework for further investigation of its molecular determinants of antigenic property and replication. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.


Antigenic evolution; Genesis; Influenza C virus; Phylogenetic evolution

PMID: 31498448 DOI: 10.1002/jmv.25589