The plant ribosome inactivating proteins luffin and saporin are potent inhibitors of HIV-1 integrase

The ribosome inactivating proteins (RIPs) are a group of proteins that are able to inactivate eukaryotic protein synthesis by attaching the 28S riboso mal RNA. Recent studies have shown that some Rips possess strong anti-human immunodeficiency virus (HIV) activity, In this study, several common plant RIPs including agrostin, gelonin, luffin, alpha-momorcharin, beta-momorcha rin, saporin and trichosanthin were examined for the ability to interfere w ith HIV-1 replication in a variety of mechanistic assays in vitro. These as says included the CD4/gp120 interaction assay, HIV-1 reverse transcriptase (RT) assay, HIV-1 protease assay and HIV-1 integrase assay. At the concentr ation of 100 nM, all RIPs appeared to enhance the CD4/gp120 interaction by about 50%. These RIPs exhibited a very weak suppressive effect on HIV-1 RT and on HIV-1 protease, In contrast, with the exception of agrostin, all the RIPs tested could strongly inhibit HIV-1 integrase, the extent of inhibiti on ranging from 26.1 to 96.3% in an ELISA-based assay. Two RIPs, saporin an d luffin, which licited over 90%, inhibition in the ELISA-based assay, were further characterized in a radiometric assay. Both of these two RIPs evoke d a strong dose-dependent inhibition in the 3'-end processing and strand-tr ansfer activities of integrase, The results from this study suggest that th e anti-HIV property of Rips may be due to inhibition of HIV-1 integrase. (C ) 2000 Federation of European Biochemical Societies.