Temporal and gene reassortment analysis of influenza C outbreaks in Hong Kong SAR, China

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From 2014 to week 07/2020 the Centre for Health Protection in Hong Kong conducted screening for influenza C virus (ICV). A retrospective analysis of ICV detections to week 26/2019 revealed persistent low-level circulation with outbreaks occurring biennially in the winters of 2015-16 and 2017-18 (1). Here we report on an outbreak occurring in 2019-20, reinforcing the observation of biennial seasonality in Hong Kong. All three outbreaks occurred in similar time-frames, were subsequently dwarfed by seasonal epidemics of influenza types A and B, and were caused by similar proportions of C/Kanagawa/1/76 (K-)lineage and C/São Paulo/378/82 S1- and S2-sublineage viruses. Ongoing genetic drift was observed in all genes, with some evidence of amino acid substitution in the HEF glycoprotein possibly associated with antigenic drift. A total of 61 ICV genomes covering the three outbreaks were analysed for reassortment and nine different reassortant constellations were identified, one K-lineage, four S1-sublineage and four S2-sublineage, with six of these being identified first in the 2019-20 outbreak (two S2-lineage and four S1-lineage). The roles that virus interference/enhancement, ICV persistent infection, genome evolution and reassortment might play in the observed seasonality of ICV in Hong Kong are discussed. Importance Influenza C virus (ICV) infection of humans is common with the great majority of people being infected during childhood, though re-infection can occur throughout life. While infection normally results in 'cold-like' symptoms, severe disease cases have been reported in recent years. However, knowledge of ICV is limited due to poor systematic surveillance and an inability to propagate the virus in large amounts in the laboratory. Following recent systematic surveillance in Hong Kong SAR, China and direct ICV gene sequencing from clinical specimens a two-year cycle of disease outbreaks (epidemics) has been identified with gene mixing playing a significant role in ICV evolution. Studies like those reported here are key to developing an understanding of the impact of influenza C virus infection in humans, notably where comorbidities exist and severe respiratory disease can develop.

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