Posttranslational modifications within the HIV-1 envelope glycoprotein which restrict virus assembly and CD4-dependent infection.
Alterations in two highly conserved N-linked glycosylation sites within the gp120 envelope glycoprotein of human immunodeficiency virus type I (HIV-1) implicated in the phenotype of a noncytopathic HIV-1 variant were introduced independently and in combination into a cytopathic, infectious HIV-1 clone by site-specific mutagenesis. Neither mutation affected the synthesis of HIV-1 envelope glycoproteins. However, one of the mutations restricted the ability of HIV-1 envelope to localize on the cell membrane and thus markedly impaired virus assembly. The HIV-1 assembly defect could be overcome in trans if site-specific mutants were packaged in HeLa cells constitutively producing wild-type HIV-1 envelope glycoprotein. In addition to inefficient virus assembly, this mutation impaired the ability of the virus to infect CD4+ T cells, but did not affect CD4-independent infection of muscle cells. These results suggest additional functions of posttranslational modification in virus replication (i.e., envelope glycoprotein transport). Given that such modifications can restrict CD4-mediated uptake without affecting CD4-independent uptake, variations in posttranslational env processing between different HIV-1 genotypes may affect virus tropism in vivo.
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-5120.
S
S
Haggerty
M P
MP
Dempsey
M I
MI
Bukrinsky
L
L
Guo
M
M
Stevenson
D000595:Amino Acid Sequence; D001483:Base Sequence; D001692:Biological Transport; D015704:CD4 Antigens / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004279:DNA, Viral; D015686:Gene Products, env / Q000378:metabolism*; D006031:Glycosylation; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D006679:HIV Seropositivity / Q000382:microbiology; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011499:Protein Processing, Post-Translational; D014779:Virus Replication
D015704:CD4 Antigens; D004279:DNA, Viral; D015686:Gene Products, env; D015699:HIV Envelope Protein gp120