Rhesus macaque IFITM3 gene polymorphisms and SIV infection

Area of Science:

• Immunology
• Virology
• Genetics

Background:

• Interferon-induced transmembrane proteins (IFITMs) are key antiviral innate immune effectors.
• Human IFITM3 gene polymorphisms influence influenza A virus (FLUAV) and human immunodeficiency virus (HIV) infection severity.
• Rhesus macaques are a vital model for HIV/AIDS research, using simian immunodeficiency virus (SIV) inoculation.

Purpose of the Study:

• To investigate the antiviral role of rhesus macaque IFITM3 (rhIFITM3) against SIV and FLUAV.
• To identify and analyze rhIFITM3 gene polymorphisms.
• To determine the association between rhIFITM3 polymorphisms and SIV infection outcomes in rhesus macaques.

Main Methods:

• Cell culture assays to assess rhIFITM3 inhibition of SIV and FLUAV entry.
• Sequencing of the rhIFITM3 gene to identify polymorphisms.
• Genotyping and statistical analysis of rhIFITM3 polymorphisms in relation to SIV viral load and AIDS-free survival in two macaque cohorts.

Main Results:

• rhIFITM3 demonstrated inhibitory effects on SIV and FLUAV entry in cell culture, albeit less efficiently than human IFITM3.
• Sixteen rhIFITM3 polymorphisms were identified, with three being synonymous exonic and 13 in non-coding regions.
• In one cohort, several intronic polymorphisms showed associations with viral load or survival, but these were not consistently observed across both parameters or when accounting for MHC allele Mamu-A1*001. No significant associations were found in the second cohort.

Conclusions:

• rhIFITM3 possesses antiviral activity against SIV and FLUAV in vitro.
• Genetic variations within the rhIFITM3 gene appear to have a minimal influence on the clinical course of SIV infection in experimentally infected rhesus macaques.
• Further research may be needed to explore other genetic factors or host-pathogen interactions influencing SIV pathogenesis in this model.