Investigation on the variations in the capsid amino acid sequence of HIV-2 subtype A, HIV-1 subtype C, its influence on the susceptibility to tripartite motif 5 alpha (TRIM5 alpha) a retrovirus restriction factor and association with HIV pathogenesis

Abstract

This study was aimed to examine amino acid variations in the HIV-1 and HIV-2 capsid region influences the susceptibility to TRIM5and#945; a retrovirus restriction factor by examining the conformational structure by molecular modeling and docking experiments. Also look at this difference in susceptibility observed in the molecular modelling has got any effect on the virological and immunological markers in infected individuals and there by associated with HIV pathogenesis. There were 80 HIV-1 and 30 HIV-2 mono-infected ART naïve individuals recruited during the study period of January 2014 to October 2018. Based on the WHO clinical stage, the study participants were categorized as Asymptomatic (WHO Stage I and II) and Symptomatic (WHO Stage III and IV) groups. 52 HIV-1 and 23 HIV-2 mono-infected individuals fall under Asymptomatic (WHO Stage I and II) group. The median CD4+ T cell count among HIV-1 and HIV-2 mono-infected individuals in asymptomatic group were 429 and 472.5 cells/and#956;L respectively. In conclusion, our data showed a significant difference in the virological and immunological markers studied among HIV-1 and HIV-2 infected individuals. Based on those data HIV-1 virus has shown a higher replication capacity compared to HIV-2. The study on capsid protein analysis showed four amino acid residues of interest at 81, 119, 152 and 159 positions of HIV-2 capsid antigen that are important determinants of restriction of TRIM5and#945; activity. The significantly higher number of polymorphisms observed in the HIV-1 capsid and a faster evolution compared to the HIV-2 make HIV-1 capsid protein refractory to the TRIM5and#945; activity. This reduced TRIM5and#945; activity shown by amino acid residue variation at position 81 of HIV-2 capsid by molecular modeling method and its association with the HIV-2 viral load level may be one of the reasons for the difference in the replication of viruses observed in the HIV-1 and HIV-2 infected individuals. This may lead to a faster progression of disease among HIV-1 infected individuals compared to HIV-2 infected individuals.