Selective Pressure of Drug on MP gene of Influenza A virus
Session VII – Furuse, Yuki, Young Investigator Applicant
Title of Contribution: Selective Pressure of Drug on MP gene of Influenza A virus
Author(s): Yuki FURUSE, Akira SUZUKI, Taro KAMIGAKI, Hitoshi OSHITANI
Affiliation(s): Tohoku University, School of Medicine, Department of Virology
Abstract:
Background: 7th segment of influenza A virus, MP gene, encodes 2 proteins. M1 is a matrix protein and M2 is a membrane protein. Amantadine is an antiviral which interferes with a viral protein, M2. Point mutations in M2 gene are responsible for the acquisition of amantadine resistance. Recently, substantial increase of amantadine resistant strains of influenza A virus has been reported not only in human influenza but also in avian influenza, most of which has S31N mutation in M2 gene. We conducted the present study to clarify if the current mutation in M2 gene were caused by selective pressure of the drug in different hosts, and also tried to analyze other selective pressures on MP gene.
Materials and Methods: Sequencing data of MP gene of influenza viruses isolated from different hosts were obtained from online database. Selective pressures for entire sequences were calculated, and were compared among hosts or by temporal information. Site-by-site analyses were also conducted.
Results: Selective pressures on M2 were stronger than that on M1 for all hosts. Selective pressure on M1 for human influenza was stronger than that for avian influenza, as well as M2. Site-by-site analyses identified the specific sites in M1 responsible for positive selection. Only one position in M2 was identified as a site under positive selection among sites linked to amantadine resistance. However, most of these sites were under stronger selective pressure in human populations than in other hosts population. Furthermore, the pressures on the sites except for position 31 in M2 had gotten bigger with time in human, though we did not find any statistical significance.
Conclusion: MP gene of influenza A virus has evolved under different selective pressure on both M1 and M2. Selective pressure on M2 is stronger than on M1. There may be drug pressure on MP gene in human influenza, though the pressure does not fully explain the recent surge of drug resistant virus.
