Mechanism of Anti-HIV Activity of Ribosome Inactivating Protein, Saporin.
Ribosome inactivating proteins (RIPs) are a family of proteins produced by plants, bacteria and fungi. RIPs have specific N-glycosidase activity, and they cleave a specific glycosidic bond in a universally conserved stem and loop structure within the large ribosomal RNA of all organisms. Saporin, a cytotoxic RIP from the plant Saponaria officinalis has been earlier shown to manifest its cytotoxicity by a combination of its N-glycosidase and apoptosis inducing activities. Saporin, along with many other RIPs also has strong inhibitory activity towards HIV integrase. In the current study, using two in vitro model systems, it is established that saporin inhibits propagation of HIV-1 in host cells. Saporin also showed a potent anti-HIV-1 integrase activity in vitro. Using three active site mutants of saporin, which respectively lack N-glycosidase, apoptosis inducing or both activities, it is shown that saporin's in vitro anti-HIV-1 integrase activity is independent of its N-glycosidase activity. However, for the anti-HIV activity of saporin, the apoptosis inducing activity is important.
Santosh K
SK
Yadav
National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi-110067, India. janendra@nii.res.in.
Janendra K
JK
Batra
D019380:Anti-HIV Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D004926:Escherichia coli / Q000235:genetics; D016655:HIV Core Protein p24 / Q000378:metabolism; D015658:HIV Infections; D019427:HIV Integrase / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D054789:Ribosome Inactivating Proteins, Type 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D029750:Saponaria / Q000235:genetics; D000076985:Saporins; D018406:Virus Physiological Phenomena / Q000187:drug effects
D019380:Anti-HIV Agents; D016655:HIV Core Protein p24; D011994:Recombinant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; C514799:p24 protein, Human Immunodeficiency Virus Type 1; D019427:HIV Integrase; D000076985:Saporins; C514801:p31 integrase protein, Human immunodeficiency virus 1