Abstract: Objective To explore the resistance of influenza A（H1N1）pdm09 isolated in Guangdong Province from 2009 to 2018 to oseltamivir （Tamiflu）, and monitor the variant trend of the epidemic strain of influenza virus. Methods Strains of influenza A（H1N1）pdm09 isolated from Guangdong Provincial Network Laboratories from 2009 to 2018 were selected （at least 1-2 strains per year in each network laboratory）.The IC50s of strains were detected by using fluorescence-based neutralization inhibition assay to select suspicious oseltamivir-resistant strains. At the same time, 112 strains of influenza A （H1N1） pdm09 virus nucleic acid were extracted and neuraminic acid （NA） gene of the virus was amplified by RT-PCR. Viral nucleic acid sequencing and bioinformatics software were used to analyze amino acid loci and gene mutations related to drug resistance of NA gene. Result Five strains（1.76%） were resistant to oseltamivir, had mutation in H275Y locus （according to N1 coding sequence）, i.e., amino acid locus 275 was all mutaed from 275H （histidine） to 275Y （tyrosine）, and then identified as Tamiflu resistant strains. The NA genes of A（H1N1）pdm09 strains isolated in Guangdong Province from 2009 to 2018 were clustered by year, and new evolutionary clusters appeared over time with a certain period of time. Conclusion Influenza A（H1N1）pdm09 virus has a very low resistance and still sensitive to oseltamivir in Guangdong Province. It is necessary to conduct surveillance of antiviral resistance of influenza virus continuously.

Key words: Influenza A virus, Oseltamivir, Resistance, Gene