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

Toshio Murakami, Toshio Hattori, Kiyoshi Takatsuki

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 μM) and chymostatin (IC50 = 4.8 μM). 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 μM). The inhibition was still observed at low temperature (IC50 = 4.7 μM) 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.

Original languageEnglish
Pages (from-to)279-284
Number of pages6
JournalBiochimica et Biophysica Acta (BBA)/Protein Structure and Molecular
Volume1079
Issue number3
DOIs
Publication statusPublished - 1991 Sep 20

Keywords

  • Human immunodeficiency virus type 1
  • Virus neutralizing domain

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology

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