a review of mutations and molecular markers associated with human transmission in iranian h9n2 isolates: a historical perspective

Since its emergence in humans in 1998, the h9n2 avian influenza virus has posed a significant threat to global public health and more than 100 cases of human infections are reported by who by 2021. despite typically mild human symptoms, the potential for human-to-human transmission, as demonstrated by other influenza viruses such as h5 and h7, warrants ongoing surveillance and research. the widespread circulation of the virus within the country s poultry industry, coupled with factors such as vaccination pressure, has contributed to its evolution and the emergence of novel isolates. genetic analysis of iranian h9n2 isolates has revealed mutations in key viral proteins, including the hemagglutinin (ha) receptor binding site, neuraminidase (na) and polymerase basic 2 (pb2(. these changes subsequently lead to a shift in the virus s tropism for mammalian cell receptors, variations in viral replication kinetics, and modification of the virus s host range. notably, mutations such as the q226l substitution in the ha protein gene and e627k in the pb2 protein, along with others in various viral proteins, have been experimentally validated to enhance the virus s ability to infect human cells. understanding the molecular determinants of h9n2 virulence and transmission is crucial for developing effective prevention and control measures. rigorous surveillance and genetic characterization of circulating isolates in iran is essential to monitor the virus s evolution and identify potential risks to human health.