BACKGROUND:

Emerging influenza A/H3N2 clades have been associated with M1 gene mutations which affect the performance of commercial PCR assays.

OBJECTIVES AND STUDY DESIGN:

The evolution and prevalence of problematic M1 mutations, and their associated viral clades, were investigated. All European and USA isolates from the GISAID database with both HA and M1 sequences available, collected during the respiratory seasons from the Fall of 2007 through January of 2018, were analyzed.

RESULTS:

Five M1 target region patterns, designated A-E, were observed in more than 10% of the isolates during a season, with patterns that appeared sequentially, each having one additional mutation. The C153T mutation was universal. Pattern A, which only had the single mutation, predominated between 2007/08 and 2009/10. Dual- and triple-mutation patterns (B and C) emerged in 2010/11 and 2011/12 respectively, and pattern C predominated for one season (2012/13). In 2012/13, the problematic quadruple-mutation containing C163T first appeared in 3C.2 viruses. Seasons 2013/14 and 14/15 were associated with significant viral diversity with five clades and four M1 patterns co-circulating, with different rates in Europe and the USA. Since 2014, clade 3C.2a with M1 pattern D has emerged as the predominant type. During 2016/17 season, a new quintuplet mutation pattern (E) emerged in cluster 3C.2a1 isolates.

CONCLUSIONS:

M1 target region mutations have been prevalent for more than ten years, with the number of mutations continually increasing. Often population inferences of M1 mutations can be made based on viral clade. However, gene segment reassortment can affect predictive abilities.