Molecular genetic characteristics of influenza A virus clinically isolated during 2011-2016 influenza seasons in Korea.

BACKGROUND: The influenza virus is reportedly associated with 3-5 million cases of severe illness and 250 000-500 000 deaths annually worldwide.

OBJECTIVES: We investigated the variation of influenza A virus in Korea and examined the association with death.

METHODS: A total of 13 620 cases were enrolled in the Hospital-based Influenza Morbidity & Mortality surveillance system in Korea during 2011-2016. Among these cases, a total of 4725 were diagnosed with influenza using RT-PCR (influenza A; n = 3696, influenza B; n = 928, co-infection; n = 101). We used 254 viral sequences from the 3696 influenza A cases for phylogenetic analysis using the BioEdit and MEGA 6.06 programs.

RESULTS: We found that the sequences of A/H3N2 in the 2011-2012 season belong to subgroup 3C.1, whereas the sequences in the 2012-2013 season pertain to subgroup 3C.2. The sequences in the 2013-2014 and 2014-2015 seasons involve subgroups 3C.3a and 3C.2a. The A/H1N1pdm09 subtype belongs to subgroup 6 and contains two clusters. In addition, sequence analysis confirmed the several substitutions of internal genes and gene substitutions associated with drug resistance (I222V in NA and S31N in M2) in the fatal cases. While statistical analysis found no significant associations between genetic differences in the viruses and mortality, mortality was associated with certain host factors, such as chronic lung disease.

CONCLUSIONS: In conclusion, influenza A virus clade changes occurred in Korea during the 2011-2016 seasons. These data, along with antigenic analysis, can aid in selecting effective vaccine strains. We confirmed that fatality in influenza A cases was related to underlying patient diseases, such as chronic lung disease, and further studies are needed to confirm associations between mortality and viral genetic substitutions.