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Engineering of Ribosome-inactivating Proteins for Improving the anti-HIV Efficacy
1 , 2 , * 1
1  Centre for Protein Science and Crystallography, School of Life Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China
2  Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China

Published: 14 January 2021 by MDPI in 1st International Electronic Conference on Toxins session Poster

Ribosome-inactivating proteins (RIPs) are N-glycosidases. They depurinate A-4324 in rat 28S ribosomal RNA in the conserved α-sarcin/ricin loop (α-SRL) and cease protein synthesis. Our group has shown that the internal peptide of the maize RIP precursor reduced the anti-HIV activity of the protein in infected macaque peripheral blood mononuclear cells (PBMC) and SHIV 89.6-infected Chinese rhesus macaque. We made use of the switch-on mechanism of maize RIP to incorporate HIV-1 protease recognition sequences to its internal inactivation region. Upon activation of this engineered maize RIP by HIV-1 protease in HIV-infected cells, the N-glycosidase activity and inhibitory effect on p24 antigen production in vitro and in infected human T cells were enhanced. This switch-on mechanism can also be applied to ricin A chain (RTA). RTA variants with HIV-1 protease recognition sequence at the C-terminus can be cleaved both in vitro and in HIV-infected cells. Furthermore, its antiviral effect was enhanced and the cytotoxicity towards uninfected cells was reduced. Our study provides a platform technology in creating protein toxin derivatives with increased pathogen-specific cytotoxicity.

Keywords: ribosome-inactivating protein; anti-HIV; engineering; switch-on mechanism