ABSTRACT
Transmembrane envelope protein (TM) residues 100, 105, and 128 of human immunodeficiency virus type 1 (HIV-1) strain HXB2 are potential sites for asparagine-linked oligosaccharide additions which are conserved among HIV-1 isolates, and all other lentivirus TM proteins. Site-specific mutants of each of the asparagine residues did not eliminate the ability of the virus to infect and replicate in CD4+ cells, but infectivity was reduced with all of these mutants, and syncytia induction was attenuated with two of these mutants. Studies of envelope expression of the mutant with the most severe defect demonstrated no significant effects on envelope protein synthesis, conformation, processing, multimerization, or release into the culture medium, suggesting that N-linked oligosaccharides are important in the specific fusion activity of TM.
Subject(s)
HIV Envelope Protein gp41/physiology , HIV-1/physiology , Asparagine/genetics , Asparagine/metabolism , Cell Fusion/physiology , Cell Line , Glycosylation , HIV Envelope Protein gp41/genetics , HIV Envelope Protein gp41/metabolism , HIV-1/genetics , Kinetics , Mutagenesis, Site-Directed , Precipitin Tests , Virus Replication/genetics , Virus Replication/physiologyABSTRACT
The transmembrane (TM) protein of human immunodeficiency virus type 1 has been demonstrated to be involved in viral infectivity and syncytium formation. Two highly conserved cysteine residues in the extracellular region of the TM protein are shown to be essential for processing the 160-kDa envelope precursor into the active 120- and 41-kDa mature forms.
