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

Authors

Abstract

Background and Objective: 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 Methods: 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.
 
Results: 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.
 
Conclusion: 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. 

Keywords

References

1. Li TC, Chan MC, Lee N. Clinical implication of antiviral resistance in influenza. Viruses 2015; 7(9): 4929-44. 2. Treanor JJ. Influenza Viruses. In: RA Kaslow, LR Stanberry, JW Le Duc. editors. Viral Infections of Humans- epidemiology and control. New York: Springer Science + Business Media; 2014; 455-78. 3. Saito R, Li D, Shimomura C, Masaki H, Le MQ, Nguyen HL, et al. An off-seasonal amantadine-resistant H3N2 influenza outbreak in Japan. Tohoku Journal of Experimental Medicine 2006; 210(1): 21-7. 4. Król E, Rychłowska M, Szewczyk B. Antivirals-current trends in fighting influenza. Acta biochimica Polonica 2014; 61(3): 495-504. 5. Pielak RM, Chou JJ. Influenza M2 proton channels. Biochimica et Biophysica Acta 2011; 1808(2): 522-9. 6. Abed Y, Goyette N, Boivin G. Generation and characterization of recombinant influenza A(H1N1) viruses harboring amantadine resistance mutations. Antimicrobial Agents and Chemotherapy 2005; 49(2): 556-9. 7. Nelson MI, Simonsen L, Viboud C, Miller MA, Holmes EC. The origin and global emergence of adamantine resistant A (H3N2) influenza viruses. Virology 2009; 388(2): 270-8. 8. Hayden FG, de Jong MD. Emerging influenza antiviral resistance threats. Journal of Infectious Diseases 2011; 203(1): 6-10. 9. Deyde VM, Xu X, Bright RA, Shaw M, Smith CB, Zang Y, et al. Surveillance of resistance to adamantanes among influenza A (H3N2) and A (H1N1) viruses isolated worldwide. Journal of Infectious Diseases 2007; 196(2): 249-57. 10. Bright RA, Medina MJ, Xu X, Perez-Oronoz G, Wallis TR, Davis XM, et al. Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern. Lancet 2005; 366 (9492): 1175-81. 11. Dong G, Peng C, Luo J, Wang C, Han L, Wu B, et al. Adamantane-resistant influenza A viruses in the world (1902-2013): frequency and distribution of M2 gene mutations. PLoS One 2015; 10(3): e0119115. 12. Hurt AC. The epidemiology and spread of drug resistant human influenza viruses. Current Opinion in Virology 2014; 8: 22-9. 13. Yavarian J, Azad TM, Zheng X, Gregory V, Lin YP, Hay A. Amantadine resistance in relation to the evolution of influenza A (H3N2) viruses in Iran. Antiviral Research 2010; 88(2): 193-6. 14. Yavarian J, Mokhtari Azad T, Shafiei Jandaghi NZ, Nategh R. Amantadine-resistant influenza A (H3N2) viruses in Iran. Acta Virologica 2009; 53(2): 135-8. 15. Yavarian J, Shafiei Jandaghi NZ, Naseri M, Mokhtari Azad T. Characterization of variations in PB2, NS1, M, neuraminidase and hemagglutinin of influenza A (H3N2) viruses in Iran. Jundishapur Journal of Microbiology 2014; 7(3): e9089. 16. World Health Organization. CDC protocol of realtime RTPCR for influenza A (H1N1). 2009. Available from http://www.who.int/csr/resources/publications/swineflu/CDCRealtimeRTPCR_SwineH1Assay-2009_20090430.pdf. 17. Schnell JR, Chou JJ. Structure and mechanism of the M2 proton channel of influenza A virus. Nature 2008; 451: 591-6. 18. Byarugaba DK, Ducatez MF, Erima B, Mworozi EA, Millard M, Kibuuka H, et al. Molecular epidemiology of influenza A/H3N2 viruses circulating in Uganda. PloS one 2011; 6(11): e27803. 19. Furuse Y, Suzuki A, Kamigaki T, Oshitani H. Evolution of the M gene of the influenza A virus in different host species: large-scale sequence analysis. Virology Journal 2009; 6: 67. 20. Melidou A, Kyriazopoulou V, Diza E, Alexiou S, Pierroutsakos Y. Antiviral resistance of influenza A (H3N2) strains isolated in northern Greece between 2004 and 2007. Euro Surveillance 2009; 14(4). 19104.
Daneshvar Medicine
Volume 25, Issue 3 - Serial Number 130
September and October 2017
Pages 13-18

Files

Share

How to cite

Statistics