Identification of the fusion peptide of primate immunodeficiency viruses.
Membrane fusion induced by the envelope glycoproteins of human and simian immunodeficiency viruses (HIV and SIVmac) is a necessary step for the infection of CD4 cells and for the formation of syncytia after infection. Identification of the region in these molecules that mediates the fusion events is important for understanding and possibly interfering with HIV/SIVmac infection and pathogenesis. Amino acid substitutions were made in the 15 NH2-terminal residues of the SIVmac gp32 transmembrane glycoprotein, and the mutants were expressed in recombinant vaccinia viruses, which were then used to infect CD4-expressing T cell lines. Mutations that increased the overall hydrophobicity of the gp32 NH2-terminus increased the ability of the viral envelope to induce syncytia formation, whereas introduction of polar or charged amino acids in the same region abolished the fusogenic function of the viral envelope. Hydrophobicity in the NH2-terminal region of gp32 may therefore be an important correlate of viral virulence in vivo and could perhaps be exploited to generate a more effective animal model for the study of acquired immunodeficiency syndrome.
Bosch
M L
ML
Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, MD 20892.
Earl
P L
PL
Fargnoli
K
K
Picciafuoco
S
S
Giombini
F
F
Wong-Staal
F
F
Franchini
G
G
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D004279:DNA, Viral / Q000235:genetics; D015686:Gene Products, env; D006678:HIV / Q000032:analysis*; D015488:HIV Antigens / Q000378:metabolism; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D006801:Humans; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D009154:Mutation; D012191:Retroviridae Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D015682:Retroviridae Proteins, Oncogenic; D015301:Retroviruses, Simian / Q000032:analysis*; D013329:Structure-Activity Relationship; D006377:T-Lymphocytes, Helper-Inducer / Q000382:microbiology; D014162:Transfection; D014616:Vaccinia virus / Q000235:genetics; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D014760:Viral Fusion Proteins
D004279:DNA, Viral; D015686:Gene Products, env; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D008562:Membrane Glycoproteins; D012191:Retroviridae Proteins; D015682:Retroviridae Proteins, Oncogenic; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; C059580:transmembrane protein, Simian immunodeficiency virus