Background and objectives: The influenza infection remains a significant global health challenge, it leads to illnesses that vary from mild to severe, and in certain cases, death. The innate immune response is the first line of defense against pathogen invaders; identification of variants associated with susceptibility or protection could further elucidate immune mechanisms and provide the basis for new therapeutic targets.

Materials and methods: We investigated four widely studied SNPs on the immune response to RNA infection in samples collected as part of sentinel influenza surveillance system. Of 1925 nasopharyngeal swabs collected from patients with Severe Acute Respiratory Infection (SARI) and Influenza-Like Illness (ILI), 115 samples were positive for ILI and 83 were positive for SARI. A third group of healthy individuals was also enrolled as a control. Genetic polymorphisms of the OAS3 (rs10735079), TYK2 (rs74956615) and APOBEC3G (rs8177832 and rs2294367) genes were genotyped using Human TaqMan SNP Genotyping Assays (ThermoFisher Scientific?). The association of Single Nucleotide Polymorphisms (SNPs) with ILI and SARI was investigated using SNPStats software.

Results: The rs2294367 in APOBECG3 show a strong and significant association with ILI and SARI across all genetic models, with a p-value<0.001 and OR between 2 and 6, while no association was found with rs8177832. The results for TYK2 suggest a potential protective effect, while the OAS3 SNP shows a strong and significant association with a decreased risk of Influenza infection specially with ILI group (OR<1 and p < 0.0001).

Conclusion: Our results open up a new perspective for new methods and strategies of therapy aimed to enhance the body´s natural defenses against influenza virus infection.