Mutational analysis of the fusion peptide of the human immunodeficiency virus type 1: Identification of critical glycine residues

被引:87
作者
Delahunty, MD
Rhee, I
Freed, EO
Bonifacino, JS
机构
[1] NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892
[2] NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892
基金
美国国家卫生研究院;
关键词
D O I
10.1006/viro.1996.0169
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The ability of human immunodeficiency virus type 1 (HIV-1) to fuse its membrane with the membrane of the target cell is a function of a similar to 23-amino-acid amino-terminal segment of the gp41 subunit of the envelope glycoprotein complex, known as the fusion peptide. The sequence of the fusion peptide is highly conserved among different variants of HIV-1 and is also very similar to that of HIV-2 and SIV. The fusion peptide is very hydrophobic and has a high content of glycine and alanine residues. Representation of the fusion peptide of HIV-1 as an alpha-helix predicts that most glycine residues would be found on one face of the alpha-helix. To assess the importance of the glycine residues for the fusogenic activity of the envelope glycoprotein complex, we mutagenized each glycine residue in the fusion peptide individually to a valine residue. The mutant envelope constructs were tested for their ability to induce syncytia (cell/cell fusion) and to mediate infection (virus/cell fusion) of CD4-positive cells. The results of our analyses show that two glycine residues (G(10) and G(13)) located within the sequence FLGFLG in the middle of the fusion peptide are critical for syncytium formation and for the establishment of a productive infection, whereas other glycine residues (G(3), G(5), and G(20)) are more permissive to substitutions. Mutation of each of the two phenylalanines (F-8 and F-11) of the FLGFLG sequence to valine also decreased fusion, although to a lesser extent than mutation of G(10) and G(13), These observations demonstrate that G(10) and G(13) are critical elements of the fusion peptide and suggest that, in addition to hydrophobicity, the exact amino acid composition and structure of the fusion peptide are critical for function. (C) 1996 Academic Press, Inc.
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页码:94 / 102
页数:9
相关论文
共 47 条
[31]   THE T4 GENE ENCODES THE AIDS VIRUS RECEPTOR AND IS EXPRESSED IN THE IMMUNE-SYSTEM AND THE BRAIN [J].
MADDON, PJ ;
DALGLEISH, AG ;
MCDOUGAL, JS ;
CLAPHAM, PR ;
WEISS, RA ;
AXEL, R .
CELL, 1986, 47 (03) :333-348
[32]   FUSOGENIC ACTIVITY OF SIV (SIMIAN IMMUNODEFICIENCY VIRUS) PEPTIDES LOCATED IN THE GP32 NH2 TERMINAL DOMAIN [J].
MARTIN, I ;
DEFRISEQUERTAIN, F ;
MANDIEAU, V ;
NIELSEN, NM ;
SAERMARK, T ;
BURNY, A ;
BRASSEUR, R ;
RUYSSCHAERT, JM ;
VANDENBRANDEN, M .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1991, 175 (03) :872-879
[33]   ENDOPROTEOLYTIC CLEAVAGE OF GP160 IS REQUIRED FOR THE ACTIVATION OF HUMAN IMMUNODEFICIENCY VIRUS [J].
MCCUNE, JM ;
RABIN, LB ;
FEINBERG, MB ;
LIEBERMAN, M ;
KOSEK, JC ;
REYES, GR ;
WEISSMAN, IL .
CELL, 1988, 53 (01) :55-67
[34]  
MYERS G, 1988, HUMAN RETROVIRUSES A, P68
[35]   INTERACTION OF THE HIV-1 FUSION PEPTIDE WITH PHOSPHOLIPID-VESICLES - DIFFERENT STRUCTURAL REQUIREMENTS FOR FUSION AND LEAKAGE [J].
NIEVA, JL ;
NIR, S ;
MUGA, A ;
GONI, FM ;
WILSCHUT, J .
BIOCHEMISTRY, 1994, 33 (11) :3201-3209
[36]   DISSOCIATION BETWEEN SYNCYTIA FORMATION AND HIV SPREADING - SUPPRESSION OF SYNCYTIA FORMATION DOES NOT NECESSARILY REFLECT INHIBITION OF HIV-INFECTION [J].
PANTALEO, G ;
POLI, G ;
BUTINI, L ;
FOX, C ;
DAYTON, AI ;
FAUCI, AS .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1991, 21 (07) :1771-1774
[37]   PHOSPHOLIPID INTERACTIONS OF SYNTHETIC PEPTIDES REPRESENTING THE N-TERMINUS OF HIV GP41 [J].
RAFALSKI, M ;
LEAR, JD ;
DEGRADO, WF .
BIOCHEMISTRY, 1990, 29 (34) :7917-7922
[38]   ANTIBODIES THAT INHIBIT FUSION OF HUMAN IMMUNODEFICIENCY VIRUS-INFECTED CELLS BIND A 24-AMINO ACID SEQUENCE OF THE VIRAL ENVELOPE, GP120 [J].
RUSCHE, JR ;
JAVAHERIAN, K ;
MCDANAL, C ;
PETRO, J ;
LYNN, DL ;
GRIMAILA, R ;
LANGLOIS, A ;
GALLO, RC ;
ARTHUR, LO ;
FISCHINGER, PJ ;
BOLOGNESI, DP ;
PUTNEY, SD ;
MATTHEWS, TJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (09) :3198-3202
[39]   SHEDDING AND INTERSPECIES TYPE SERO-REACTIVITY OF THE ENVELOPE GLYCOPOLYPEPTIDE GP120 OF THE HUMAN-IMMUNODEFICIENCY-VIRUS [J].
SCHNEIDER, J ;
KAADEN, O ;
COPELAND, TD ;
OROSZLAN, S ;
HUNSMANN, G .
JOURNAL OF GENERAL VIROLOGY, 1986, 67 :2533-2538
[40]   ROLE OF THE HTLV-III/LAV ENVELOPE IN SYNCYTIUM FORMATION AND CYTOPATHICITY [J].
SODROSKI, J ;
GOH, WC ;
ROSEN, C ;
CAMPBELL, K ;
HASELTINE, WA .
NATURE, 1986, 322 (6078) :470-474