Endoproteolytic cleavage of gp160 is required for the activation of human immunodeficiency virus

McCune, Joseph M.; Rabin, Linda; Feinberg, Mark B.; Lieberman, Miriam; Kosek, Jon C.; Reyes, Gregory R.; Weissman, Irving L.

doi:10.1016/0092-8674(88)90487-4

Cited by 593 publications

(422 citation statements)

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“…Env proprotein is organized as a trimer, and envelope structures are derived from a gp160 kDa precursor, gp160, which is cleaved into a gp120 external surface envelope species and gp41, a transmembrane glycoprotein. 16 The virion gp120, located at the virus surface, interacts with lymphocyte CD4 receptor to initiate the entry of HIV-1 into CD4-postive cells. 31 .…”

Section: Inhibition Of Hiv-1 Replication By a 1 Atmentioning

confidence: 99%

“…They are synthesized as inactive 160 kDa precursors, 15 and activated by endoproteolytic cleavage at the carboxyl terminus of the basic consensus sequence Arg-X-Lys/ Arg-Arg. 16,17 This sequence is recognized by the kexin/ subtilisin-like serine proteases. 18 The cellular serine protease, furin, was the first of this group that was shown to catalyze proteolytic maturation of both HIV-1 and influenza virus envelope glycoproteins.…”

Section: Introductionmentioning

confidence: 99%

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HIV-1 proprotein processing as a target for gene therapy

2003

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Section: Inhibition Of Hiv-1 Replication By a 1 Atmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

HIV-1 proprotein processing as a target for gene therapy

2003

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“…The viral surface is characteristically made up of knobs containing trimers or tetramers of the envelope glycoprotein (Gelderblom et al, 1988;Ozel et al, 1988;Pinter et a/., 1989;Weiss et al, 1990;Earl et al, 1992). The envelope glycoprotein is cleaved inside the cell from a 160 kDa precursor into a gp120 external surface (SU) envelope glycoprotein and a gp41 transmembrane (TM) protein (McCune et al, 1988). The virion gp120 located on the virus surface contains the binding site for the cellular receptor(s).…”

Section: The Human Immunodeficiency Virus Typementioning

confidence: 99%

Review

1996

Biological Chemistry Hoppe-Seyler

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Proteolytic enzymes have many physiological functions in plants, bacteria, viruses, protozoa and mammals. They play a role in processes such as food digestion, complement activation or blood coagulation. The action of proteolytic enzymes is biologically controlled by proteinase inhibitors and increasing attention is being paid to the physiological significance of these natural inhibitors in pathological processes. The reason for this growing interest is that uncontrolled proteolysis can lead to irreversible damage e.g. in chronic inflammation or tumor metastasis. This review focusses on the possible role of the cystatins, natural and specific inhibitors of the cysteine proteinases, in pathological processes. Key words: Cystatins / Cysteine proteinases / Inflammation / Inhibitors / Pathological processes. Cysteine ProteinasesCysteine Proteinases, synonymous with thiol proteinases, are small proteins with molecular masses varying from 23 to 24 kDa and with two catalytic residues, Cys25 and His159, which are involved in the hydrolytic reaction. Cysteine proteinases catalyze the hydrolysis of various polypeptide substrates and are most active under reducing and mildly acidic conditions (pH 5 -6.5). They have been detected in and isolated from a large number of biological sources including plants, bacteria, animals and humans. Bacterial cysteine proteinases are produced by Clostridium histolyticum, named clostripain, by hemolytic group A streptococci and by the pathogenic anaerobic Porphyromonas gingivalis, a bacterium associated with periodontitis. Bacterial cysteine proteinases probably play a role in the penetration of normal tissues by the bacteria and in the food digestion. Viral cysteine proteinases from picornaviruses, e.g. the poliovirus and rhinovirus type I, are involved in proteolytic cleavage of precursor proteins for virus replication and for the production of new virus particles. A virus-coded cysteine proteinase is involved in this process (Kay and Dunn, 1990; Körant et a/., 1985;. HIV-I also needs proteolytic processing by cysteine proteinases to regulate the expression of viral proteins (Guy ef a/., 1991). Protozoal cysteine proteinases are produced by a number of protozoan parasites to facilitate host invasion, metabolize host proteins, to degrade the host immune molecules or to use them for intracellular replication. Cysteine proteinases are produced by e.g. Trypanosoma cruzi, the causative agent of American trypanosomiasis or by Leishmania species, causing one of the six major parasitic diseases. Furthermore, human malarial parasites produce a broad scala of proteinases including cysteine proteinase which are involved in erythrocyte invasion and rupture (McKerrow, 1993). Mammalian cysteine proteinases are present in the lysosomes of cells. Lysosomes contain different cysteine proteinases, the most important being the cathepsins B, H, L and S Kirschke, 1981, Barrett et a/., 1988). These cathepsins have common ancestors and are related to papain. Cathepsin B has been detected in every tissue or cel...

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“…In the case of HIV-1, the viral envelope proprotein gp160 must undergo proteolytic cleavage by cellular serine proteases to liberate its active peptide subfragments, gp120 and gp41. 1 In addition, HIV protease (PR) processes the HIV Gag and Gag-Pol polyproteins to release a large number of mature proteins that are obligatory for HIV viral particle assembly and maturation, and for virion progeny to be infectious. 2 Gene delivery to cultured human lymphocyte cell lines and primary human lymphocyte provides expression of native human a 1 -antitrypsin (a 1 AT), a serine protease inhibitor, 3 that these cells do not normally express.…”

mentioning

confidence: 99%