Actinohivin, a novel anti-HIV protein from an actinomycete that inhibits syncytium formation: Isolation, characterization, and biological activities

Blocking human immunodeficiency virus (HIV) entry into target cells is an i mportant goal of HIV and acquired immune deficiency syndrome (AIDS) therapi es. We have searched for anti-HIV substances from microorganisms using a sy ncytium formation assay system constructed with HeLa/CD4/Lac-Z and HeLa/T-e nv/Tat cells, We discovered a novel anti-HIV protein that inhibits syncytiu m formation, designated as actinohivin, from a cultured broth of a soil iso late, actinomycete strain K97-0003. ESI mass spectrometry of actinohivin is olated from the culture filtrate showed an ion with molecular mass of 12,52 0.3 De. The amino acid sequence was determined by N-terminal Edman degradat ion of the intact protein and peptide fragments formed by endoproteinase di gestions. Actinohivin consists of a 114-amino-acid chain that exhibits inte rnal sequence triplication. Actinohivin inhibited both T-cell and macrophag e tropic syncytium formation, with IC50 values of 60 and 700 nM, respective ly, and the cytopathic effect of HIV-1(IIIB) in MT-4 cells, with IC50 value of 230 nM, (C) 2001 Academic Press.