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 attacking the 28S ribosomal 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-momorcharin, saporin and trichosanthin were examined for the ability to interfere with HIV-1 replication in a variety of mechanistic assays in vitro. These assays included the CD4/gp120 interaction assay, HIV-1 reverse transcriptase (RT) assay, HIV-1 protease assay and HIV-1 integrase assay. At the concentration 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 inhibition ranging from 26.1 to 96.3% in an ELISA-based assay. Two RIPs, saporin and luffin, which licited over 90% inhibition in the ELISA-based assay, were further characterized in a radiometric assay. Both of these two RIPs evoked a strong dose-dependent inhibition in the 3'-end processing and strand-transfer activities of integrase. The results from this study suggest that the anti-HIV property of RIPs may be due to inhibition of HIV-1 integrase.
Au
T K
TK
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
Collins
R A
RA
Lam
T L
TL
Ng
T B
TB
Fong
W P
WP
Wan
D C
DC
D019380:Anti-HIV Agents / Q000494:pharmacology; D015704:CD4 Antigens / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D019427:HIV Integrase / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D016333:HIV Protease / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D000922:Immunotoxins; D020128:Inhibitory Concentration 50; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000494:pharmacology*; D010944:Plants / Q000737:chemistry; D011485:Protein Binding / Q000187:drug effects; D012269:Ribosomal Proteins; D054788:Ribosome Inactivating Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism; D000076985:Saporins; D015978:Trichosanthin / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D019428:HIV Integrase Inhibitors; D017320:HIV Protease Inhibitors; D000922:Immunotoxins; D010940:Plant Proteins; D012269:Ribosomal Proteins; D054789:Ribosome Inactivating Proteins, Type 1; C459705:agrostin protein, Agrostemma; C063258:luffin-a protein, Luffa cylindrica; C069038:luffin-b protein, Luffa cylindrica; D015978:Trichosanthin; C025674:GEL protein, Gelonium multiflorum; C039582:MMC protein, Momordica charantia; D019427:HIV Integrase; D054303:HIV Reverse Transcriptase; D009699:N-Glycosyl Hydrolases; D054788:Ribosome Inactivating Proteins; D000076985:Saporins; D016333:HIV Protease