Original Article

Genetic variations on influenza virus infection outcomes in Moroccan patients

Abstract

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.

1. Li Y, Banerjee S, Wang Y, Goldstein SA, Dong B, Gaughan C, et al. Activation of RNase L is dependent on OAS3 expression during infection with diverse human viruses. Proc Natl Acad Sci U S A 2016; 113: 2241-2246.
2. Prchal-Murphy M, Semper C, Lassnig C, Wallner B, Gausterer C, Teppner-Klymiuk I, et al. TYK2 Kinase Activity Is Required for Functional Type I Interferon Responses In Vivo. Lenz LL, editor. PLoS One 2012; 7(6): e39141.
3. Reddy K, Winkler CA, Werner L, Mlisana K, Abdool Karim SS, Ndung’u T, et al. APOBEC3G expression is dysregulated in primary HIV-1 infection and polymorphic variants influence CD4+ T-cell counts and plasma viral load. AIDS 2010; 24: 195-204.
4. Iqbal K, Imran M, Ullah S, Jamal M, Waheed Y. Correlation of apolipoprotein B mRNA-editing enzyme, catalytic polypeptide- like 3G genetic variant rs8177832 with HIV-1 predisposition in Pakistani population. Curr HIV Res 2019; 16: 297-301.
5. Sadeghpour S, Khodaee S, Rahnama M, Rahimi H, Ebrahimi D. Human APOBEC3 variations and viral infection. Viruses 2021; 13: 1366.
6. Pauli EK, Schmolke M, Hofmann H, Ehrhardt C, Flory E, Münk C, et al. High level expression of the anti-retroviral protein APOBEC3G is induced by influenza A virus but does not confer antiviral activity. Retrovirology 2009; 6: 38.
7. Jonathan M, Ikeda T. APOBEC3 family proteins as drivers of virus evolution. Front Virol 2023; 3: 1332010.
8. El Houdi M, Skhoun H, El Fessikh M, Benmansour R, El Yousfi FZ, Nebhani C, et al. Association study of the JAK/STAT signaling pathway with susceptibility to COVID-19 in moroccan patient and in-silico analysis of rare variants. Virus Res 2025; 351: 199509.
9. Seidl T, Whittall T, Babaahmady K, Lehner T. B‐cell agonists up‐regulate AID and APOBEC3G deaminases, which induce IgA and IgG class antibodies and anti‐viral function. Immunology 2012; 135: 207-215.
10. Belbacha I, Azzouzi ME, Bensghir R, Marhoum KF, Hajjout K, Elharti EM, et al. The APOBEC3G gene rs2294367 (C>G) variant is associated with HIV-1 infection in Moroccan subjects. Acta Trop 2024; 249: 107045.
11. Simonović N, Witalisz-Siepracka A, Meissl K, Lassnig C, Reichart U, Kolbe T, et al. NK Cells require cell-extrinsic and -intrinsic TYK2 for full functionality in tumor surveillance and antibacterial immunity. J Immunol 2019; 202: 1724-1734.
12. Kreins AY, Ciancanelli MJ, Okada S, Kong XF, Ramírez-Alejo N, Kilic SS, et al. Human TYK2 deficiency: Mycobacterial and viral infections without hyper-IgE syndrome. J Exp Med 2015 ; 212: 1641-1662.
13. Gracias S, Chazal M, Decombe A, Unterfinger Y, Sogues A, Pruvost L, et al. Tick‐borne flavivirus NS5 antagonizes interferon signaling by inhibiting the catalytic activity of TYK2. EMBO Rep 2023; 24(12): e57424.
14. Loi E, Moi L, Cabras P, Arduino G, Costanzo G, Del Giacco S, et al. HLA-C dysregulation as a possible mechanism of immune evasion in SARS-CoV-2 and other RNA-virus infections. Front Immunol 2022; 13: 1011829.
15. Ma DY, Suthar MS. Mechanisms of innate immune evasion in re-emerging RNA viruses. Curr Opin Virol 2015; 12: 26-37.
16. Perez-Favila A, Sanchez-Macias S, De Lara SAO, Garza-Veloz I, Araujo-Espino R, Castañeda-Lopez ME, et al. Gene variants of the OAS/RNase L pathway and their association with severity of symptoms and outcome of SARS-CoV-2 infection. J Pers Med 2024; 14: 426.
17. Lin RJ, Yu HP, Chang BL, Tang WC, Liao CL, Lin YL. Distinct Antiviral Roles for Human 2′,5′-oligoadenylate synthetase family members against Dengue virus infection. J Immunol 2009; 183: 8035-8043.
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IssueVol 18 No 3 (2026) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijm.v18i3.21662
Keywords
Influenza SARI ILI APOBEC3G OAS3 TYK2 Single nucleotide polymorphisms
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Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Ihazmade H, Regragui Z, Bimouhen A, Belbacha I, Falaki F, Benfathallah B, Elharti E, Triki S, Sadki K, Oumzil H. Genetic variations on influenza virus infection outcomes in Moroccan patients. Iran J Microbiol. 2026;18(3):357-366.