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History of matrix genes mutations within PCR target regions among circulating influenza H3N2 clades over
1Department of Pathology and Laboratory Medicine, Albany Medical Center Hospital and Albany Medical College, MC-22 43 New Scotland Ave., Albany, NY 12208, United States.
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.
Insights
Emerging influenza A/H3N2 clades show increasing M1 gene mutations, impacting PCR assay performance. These mutations, evolving over a decade, necessitate ongoing monitoring for accurate influenza surveillance.
Area of Science:
- Virology
- Molecular Epidemiology
- Public Health
Background:
- Emerging influenza A/H3N2 clades are linked to M1 gene mutations.
- These mutations can compromise the effectiveness of standard PCR diagnostic assays.
Purpose of the Study:
- To investigate the evolution and prevalence of M1 gene mutations in influenza A/H3N2.
- To identify associated viral clades and track mutation patterns over time.
Main Methods:
- Analysis of influenza A/H3N2 isolates from GISAID database (Europe and USA, 2007-2018).
- Sequencing data for HA and M1 genes were utilized.
- M1 target region mutation patterns (A-E) were identified and tracked.
Main Results:
- Five distinct M1 mutation patterns (A-E) were observed, appearing sequentially with increasing mutations.
- The C153T mutation was universally present; pattern D (associated with clade 3C.2a) became predominant after 2014.
- Significant viral diversity and co-circulation of multiple M1 patterns were noted, with regional differences between Europe and the USA.
Conclusions:
- M1 gene mutations in influenza A/H3N2 have been prevalent for over a decade, with a continuous increase in mutation complexity.
- While M1 mutations often correlate with viral clades, gene segment reassortment can impact predictive accuracy for surveillance.
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