Interaction of Human Immunodeficiency Virus-1 and Human Immunodeficiency Virus-2 Capsid Amino Acid Variants with Human Tripartite Motif 5α Protein SPRY Domain and its Association with Pathogenesis

Purpose: The sequence variation of human immunodeficiency virus (HIV) capsid region may influence and alter the susceptibility to human tripartite motif 5 alpha protein (huTRIM5 alpha). Materials and Methods: Molecular docking was carried out with huTRIM5 alpha SPRY domain by the use of ClusPro and Hex docking program for HIV-1 and HIV-2 capsid sequences. Results: The sequence analysis on HIV-1 and HIV-2 capsid gag gene identified 35 (19.7%) single-nucleotide polymorphisms (SNPs) in HIV-1 and 8 (4.5%) SNPs in HIV-2. The variations observed in the HIV-2 capsid region were significantly lower than HIV-1 (P < 0.001). The molecular docking analysis showed that HIV-1 wild type used V1 loop, while HIV-2 used V3 loop of huTRIM5 alpha for interaction. HIV-1 with A116T SNP and HIV-2 with V81A SNP use V3 and V1 loop of huTRIM5 alpha for interaction respectively. The reduced huTRIM5 alpha inhibition may lead to a faster progression of disease among HIV-1-infected individuals. However, in case of HIV-2, increased inhibition by huTRIM5 alpha slows down the disease progression. Conclusion: Polymorphisms in the capsid protein with both HIV-1- and HIV-2-monoinfected individuals showed the difference in the docking energy from the wild type. This is the first study which documents the difference in the usage of loop between the two HIV types for interaction with huTRIM5 alpha. Variations in the capsid protein result in alteration in the binding to the restriction factor huTRIM5 alpha.