A principal neutralizing domain of human immunodeficiency virus type 1 interacts with proteinase-like molecule(s) at the surface of Molt-4 clone 8 cells.

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A principal neutralizing domain of human immunodeficiency virus type 1 interacts with proteinase-like molecule(s) at the surface of Molt-4 clone 8 cells.

Biochim Biophys Acta. 1991 Sep 20;1079(3):279-84. Unique Identifier : AIDSLINE MED/92002146
Murakami T; Hattori T; Takatsuki K; Second Department of Internal Medicine, Kumamoto University; Medical School, Japan.

Abstract: A principal neutralizing domain (PND) of the major envelope glycoprotein (gp120) of the HTLV-III BH10 strain of human immunodeficiency virus type 1 (HIV-1) has significant amino acid similarities to a reactive site of Kunitz-type basic proteinase inhibitors. We therefore thought that the PND may interact with cellular proteinase-like molecule(s) upon HIV-1 infection and measured the cellular proteolytic activities at the surface of intact Molt-4 clone 8 cells, which are highly susceptible to HIV-1 infection. The cells preferentially cleaved succinyl-Leu-Leu-Val-Tyr-4-methylcoumaryl-7-amide, a good substrate of chymotrypsin, and the activity was strongly inhibited by N-tosyl-L-phenylalanyl chloromethyl ketone (IC50 = 11.5 microM) and chymostatin (IC50 = 4.8 microM). A synthetic peptide of 24 residues (amino acids 308-331) that correspond to the PND also inhibited the cellular proteolytic activity in a dose-dependent manner (IC50 = 79.2 microM). The inhibition was still observed at low temperature (IC50 = 42.7 microM) and even after the peptide-treated cells were washed. We therefore think that the peptide interacts with proteinase-like molecule(s) located at the surface of the cells. The synthetic peptides from four other strains of HIV-1 corresponding to the PND similarly inhibited the proteolytic activity. These results may be helpful to clarify the novel mechanism(s) for HIV-1 infection.

Keywords: Amino Acid Sequence Cell Line Cell Membrane/ENZYMOLOGY Comparative Study Human HIV Envelope Protein gp120/*METABOLISM HIV-1/*PHYSIOLOGY Molecular Sequence Data Peptide Peptidohydrolases/*METABOLISM Peptides/CHEMICAL SYNTHESIS Sequence Homology, Nucleic Acid Substrate Specificity Support, Non-U.S. Gov't Trypsin Inhibitor, Kunitz Soybean JOURNAL ARTICLE

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