title: Antiviral drug profile of human influenza A & B viruses circulating in India: 2004-2011.
abstract: OBJECTIVE
  Recent influenza antiviral resistance studies in South East Asia, Europe and the United States reveal adamantane and neuraminidase inhibitor (NAIs) resistance. This study was undertaken to evaluate antiviral resistance in influenza viruses isolated from various parts of India, during 2004 to 2011.
  
  
  METHODS
  Influenza viruses were analyzed genetically for known resistance markers by M2 and NA gene sequencing. Influenza A/H1N1 (n=206), A/H3N2 (n=371) viruses for amantadine resistance and A/H1N1 (n=206), A/H3N2 (n=272) and type B (n=326) for oseltamivir resistance were sequenced. Pandemic (H1N1) (n=493) isolates were tested for H274Y mutation by real time reverse transcription (rRT)-PCR. Randomly selected resistant and sensitive influenza A/H1N1 and A/H3N2 viruses were confirmed by phenotypic assay.
  
  
  RESULTS
  Serine to asparagine (S3IN) mutation was detected in six isolates of 2007-2008. One dual-resistant A/H1N1 was detected for the first time in India with leucine to phenylalanine (L26F) mutation in M2 gene and H274Y mutation in NA gene. A/H3N2 viruses showed an increase in resistance to amantadine from 22.5 per cent in 2005 to 100 per cent in 2008 onwards with S3IN mutation. Fifty of the 61 (82%) A/H1N1 viruses tested in 2008-2009 were oseltamivir resistant with H274Y mutation, while all A/H3N2, pandemic A/H1N1 and type B isolates remained sensitive. Genetic results were also confirmed by phenotypic analysis of randomly selected 50 resistant A/H1N1 and 40 sensitive A/H3N2 isolates.
  
  
  CONCLUSIONS
  Emergence of influenza viruses resistant to amantadine and oseltamivir in spite of negligible usage of antivirals emphasizes the need for continuous monitoring of antiviral resistance.
authors.affiliation: National Institute of Virology (ICMR), Pune, India.
authors.forename: V A
authors.initials: VA
authors.lastname: Potdar
authors.forename: M R
authors.initials: MR
authors.lastname: Dakhave
authors.forename: P B
authors.initials: PB
authors.lastname: Kulkarni
authors.forename: S A
authors.initials: SA
authors.lastname: Tikhe
authors.forename: S
authors.initials: S
authors.lastname: Broor
authors.forename: P
authors.initials: P
authors.lastname: Gunashekaran
authors.forename: M
authors.initials: M
authors.lastname: Chawla-Sarkar
authors.forename: A
authors.initials: A
authors.lastname: Abraham
authors.forename: D
authors.initials: D
authors.lastname: Bishwas
authors.forename: K N
authors.initials: KN
authors.lastname: Patil
authors.forename: A A
authors.initials: AA
authors.lastname: Kadam
authors.forename: S S
authors.initials: SS
authors.lastname: Kode
authors.forename: A C
authors.initials: AC
authors.lastname: Mishra
authors.forename: M S
authors.initials: MS
authors.lastname: Chadha
mesh_terms: D000547:Amantadine; D001483:Base Sequence; D016000:Cluster Analysis; D024882:Drug Resistance, Viral / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D007194:India; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics*; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics*; D009981:Influenza B virus / Q000235:genetics*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D053139:Oseltamivir; D010802:Phylogeny; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D005819:Genetic Markers; D053139:Oseltamivir; D000547:Amantadine