Growth Kinetics of Influenza C Virus Antigenic Mutants That Escaped from Anti-Hemagglutinin Esterase Monoclonal Antibodies and Viral Antigenic Changes Found in Field Isolates.

Yoko Matsuzaki,Katsumi Mizuta,Seiji Hongo,Yoko Kadowaki,Kanetsu Sugawara,Yoshitaka Shimotai,Hidekazu Nishimura

doi:10.3390/v13030401

Abstract

The antigenicity of the hemagglutinin esterase (HE) glycoprotein of influenza C virus is known to be stable; however, information about residues related to antigenic changes has not yet been fully acquired. Using selection with anti-HE monoclonal antibodies, we previously obtained some escape mutants and identified four antigenic sites, namely, A-1, A-2, A-3, and Y-1. To confirm whether the residues identified as the neutralizing epitope possibly relate to the antigenic drift, we analyzed the growth kinetics of these mutants. The results showed that some viruses with mutations in antigenic site A-1 were able to replicate to titers comparable to that of the wild-type, while others showed reduced titers. The mutants possessing substitutions in the A-2 or A-3 site replicated as efficiently as the wild-type virus. Although the mutant containing a deletion at positions 192 to 195 in the Y-1 site showed lower titers than the wild-type virus, it was confirmed that this region in the 190-loop on the top side of the HE protein is not essential for viral propagation. Then, we revealed that antigenic changes due to substitutions in the A-1, A-3, and/or Y-1 site had occurred in nature in Japan for the past 30 years. These results suggest that some residues (i.e., 125, 176, 192) in the A-1 site, residue 198 in the A-3 site, and residue 190 in the Y-1 site are likely to mediate antigenic drift while maintaining replicative ability.

Highlights

Influenza C virus was first isolated in 1947 (C/Taylor/1233/1947) from the throat washings of a man living in New York City who had a mild headache and backache and coryza [1]
To resolve the problem regarding the functional constraints on variation in the antigenic region, we examined the growth kinetics of these escape mutants and found some residues that affect the antigenicity while retaining replicative fitness
We previously reported that some escape mutants of C/Ann Arbor/1/50 (C/Taylor lineage) and C/Yamagata/15/2004 (C/Yamagata lineage) have reduced Hemagglutination inhibition (HI) activity against the monoclonal antibodies (MAbs) used for selection [26]

Summary

Introduction

Influenza C virus was first isolated in 1947 (C/Taylor/1233/1947) from the throat washings of a man living in New York City who had a mild headache and backache and coryza [1]. Influenza C virus can infect humans of all age groups [2,3], children account for the vast majority of clinical cases. This virus causes a mild upper respiratory tract illness in children and can causes lower respiratory tract illness, such as bronchitis and pneumonia, in children < 2 years old [2,4,5,6] or in patients with comorbidities [2]. Since 1988, we have continuously monitored influenza C virus infections in Japan using a cell culture method and have carried out antigenic analysis of isolated strains. Among the six HE lineages, five lineages, excepting C/Taylor, circulated in Japan between 1988 and 2018 [7,10,11,12,13,14,15,16,17,18,19]

Methods

Results

Conclusion