Adamantane-resistant influenza a viruses in the world (1902-2013): frequency and distribution of M2 gene mutations.

Abstract

Adamantanes (amantadine and rimantadine) have been used to prevent and treat influenza A virus infections for many years; however, resistance to these drugs has been widely reported in the world. To investigate the frequency and distribution of M2 gene mutations in adamantane-resistant influenza variants circulated in the world between 1902 and 2013, 31251 available M2 protein sequences from different HA-subtype influenza A viruses (H1-H17) were analyzed and adamantane resistance-associated mutations were compared (L26F, V27A, A30T, A30V, S31N, G34E, and L38F). We find that 45.2% (n = 14132) of influenza A (H1-H17) viruses circulating globally were resistant to adamantanes, and the vast majority of resistant viruses (95%) bear S31N mutations. Whereas, only about 1% have V27A mutations and other mutations (L26F, A30T, G34E, and L38F) were extremely rare (their prevalence appeared to be < 0.2%). Our results confirm that H1, H3, H5, H7, H9, and H17 subtype influenza A viruses exhibit high-level resistance to adamantanes. In contrast, the appearance of adamantane-resistant mutants in H2, H4, H6, H10, and H11 subtypes was rare. However, no adamantane resistance viruses were identified among other HA subtypes (H8, H12-H16). Our findings indicate that the frequency and distribution of adamantane-resistant influenza variants varied among different HA subtypes, host species, years of isolation, and geographical areas. This comprehensive study raises concerns about the increasing prevalence of adamantane-resistant influenza A viruses and highlights the importance of monitoring the emergence and worldwide spread of adamantane-resistant variants.

• Authors: Guoying Dong, Chao Peng, Jing Luo, Chengmin Wang, Le Han, Bin Wu, Guangju Ji, Hongxuan He
• Journal: PloS one (PLoS One) Vol. 10 Issue 3 Pg. e0119115 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 25768797 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• M2 protein, Influenza A virus
• Viral Matrix Proteins
• Adamantane

Topics

• Adamantane (therapeutic use)
• Antiviral Agents (therapeutic use)
• Drug Resistance, Viral (genetics)
• Humans
• Influenza A virus (genetics)
• Influenza, Human (drug therapy, virology)
• Mutation (genetics)
• Viral Matrix Proteins (genetics)