Survey of M2 gene sequence of influenza viruses isolated from Iranian patients in 2014 for determination of adamantane resistance

Adamantanes, amantadine, and rimantadine have been used for many years for prevention and treatment of influenza virus A infections. These drugs are influenza virus M2 protein inhibitors and some amino acids substitutions in transmembrane portion of this protein cause resistance to them. This study was done for survey of adamantane resistance related nucleotide sequence changes in M2 gene of H1N1 and H3N2 subtypes isolated from Iranian patients in 2014.
Materiasl and Nasal swabs of patients with influenza-like symptoms were collected from Tehran through winter 2014 and were examined by Real Time Reverse Transcription PCR to evaluate presence of subtypes of H1N1 and H3N2 of influenza viruses A in them. Then, some positive samples for these viruses were propagated in cell culture. Four isolates from each subtype were randomly selected for M gene amplification by Reverse Transcription PCR and genetic analysis.
The study of point mutations in M2 gene sequence of isolates showed presence of most prevalent adamantane resistance related mutation; substitutions of serine with asparagine in amino acid 31; in all of them. Other mutations conferring resistance to adamantanes were not found.
According to results of this study and reports from other investigators, which showed the high prevalence of adamantane resistant mutants in human influenza virus A isolates, it is recommended that adamantanes not be used for the treatment of influenza.