Asian Institute of Technology & Management, Purbanchal University, Khumaltar, Lalitpur
Posters & Accepted Abstracts: J Antivir Antiretrovir
Toll like receptor (TLR7/8) are potential for production of Interferon type I (INF-I) molecules, which are known for their anti-viral activity. Here we report a synthetic siRNA-fusion peptide based complex that enabled the INF-I production via TLR7/8 and also inhibited Nef mediated MHC class I (MHC-I) down regulation in HIV-1 infected cells. We reported recycling of Nef transported MHC-I from late endosome/early lysosome using TBEVsE (Tick-borne encephalitis virus soluble Envelope) peptide with conserved His323 residue. TBEVsE fusogenic complex was able to salvage intact heavy chain-Ã?Â²2m heterodimer with HIV-1 antigen bounded confirmation, resembling the cross presentation of MHC-I. Rescued MHC-I was then circulated back to the cell surface and thus up regulated CD8+ CTL activity in HIV-1 infected cells. The synthetic silencing pathway also differentially silenced MYD88 in vitro hindering the initiation of INF-I related inflammosomes. This study indicates that there are in fact possibilities for intracellular vaccine mechanism which can harness innate as well humoral immune system against HIV. It shows great potential since transplantation of engineered haematopoetic stem cells expressing the mechanism we reported here can be a potent weapon against chronic viral infection like HIV.
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