Actinohivin, a novel anti-human immunodeficiency virus protein from an actinomycete, inhibits viral entry to cells by binding high-mannose type sugar chains of gp120.
We searched human immunodeficiency virus (HIV) entry inhibitors and found a novel anti-HIV protein, actinohivin (AH), in a culture filtrate of the newly discovered genus actinomycete Longispora albida gen. nov., sp. nov. This paper deals with the mechanism of action of the anti-HIV activity of AH. AH exhibited potent anti-HIV activities against various strains of HIV-1 and HIV-2. AH bound to the glycoprotein gp120 of various strains of HIV-1 and gp130 of simian immunodeficiency virus (SIV), but did not bind to non-glycosylated gp120 nor to cells having CD4 and coreceptors, suggesting that AH inhibits viral entry to cells by binding to the envelope glycoprotein. The investigation of the effects of various sugars on AH-gp120 binding by ELISA revealed that yeast mannan alone strongly inhibited the binding (IC50 = 3.0 microg/ml). Experiments investigating the binding of AH to other glycoproteins revealed that AH binds to ribonuclease B and thyroglobulin that have a high-mannose type saccharide chain, but not to other glycoproteins having a N-glycoside type saccharide chain. The above results indicate that high-mannose type saccharide chains of gp120 are molecular targets of AH in its anti-HIV activity.
Chiba
Harumi
H
School of Pharmaceutical Sciences, Kitasato University, Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Inokoshi
Junji
J
Nakashima
Hideki
H
Omura
Satoshi
S
Tanaka
Haruo
H
D039903:Actinobacteria / Q000737:chemistry; D019380:Anti-HIV Agents / Q000378:metabolism / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D015726:Giant Cells / Q000187:drug effects; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism; D006678:HIV / Q000187:drug effects / Q000502:physiology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006384:Hemagglutination; D006801:Humans; D008358:Mannose / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism
D019380:Anti-HIV Agents; D001426:Bacterial Proteins; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D006023:Glycoproteins; D015699:HIV Envelope Protein gp120; D019718:Receptors, CXCR4; D011991:Receptors, Virus; D014764:Viral Proteins; C424136:actinohivin protein, actinomycete; D008358:Mannose