Biological characterization of noninfectious HIV-1 particles lacking the envelope protein

• Published in: Virology (New York, N.Y.) Vol. 187; no. 2; pp. 604 - 611
• Main Authors: Reza Sadaie, M., Kalyanaraman, Vaniambadi S., Mukopadhayaya, Robin, Tschachler, Erwin, Gallo, Robert C., Wong-Staal, Flossie
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.04.1992; Elsevier
• Subjects: AIDS/HIV; Animals; Biological and medical sciences; Cercopithecus aethiops; Defective Viruses - growth & development; DNA Mutational Analysis; Fundamental and applied biological sciences. Psychology; Gene Products, env - genetics; Genes, env; HIV Core Protein p24 - metabolism; HIV Infections - microbiology; HIV-1 - genetics; HIV-1 - pathogenicity; Humans; In Vitro Techniques; Macrophages - microbiology; Microbiology; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Tumor Cells, Cultured; Virology; Virus Replication; Virus; Proteins; HIV-1 virus; Virus like particle; Infectivity; Retroviridae; Lentivirinae; Human immunodeficiency virus; Mutation; Defectivity; Virus envelope
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/0042-6822(92)90462-X

To understand the role of the HIV-1 envelope protein in the assembly of virus, we constructed a proviral clone of HIV-1 where the methionine initiator codon of the env gene was substituted with a translational stop codon. Upon DNA transfection into permissive cells in culture, this clone produces virus-like particles similar in size to parental virus but are noninfectious in human T-cells, promonocytic cells, and primary macrophages. This mutant readily recombines with a deletion mutant provirus lacking the entire gag-pol region producing a recombinant virus that is infectious. Substitution of the same initiator methionine codon with valine results in a leaky missense mutant provirus capable of a low level of Env protein synthesis that leads to a productive infection. Thus, the prototype initiation codon AUG is dispensable for virus infectivity. Further, the expression of the envelope protein is not a prerequisite for the assembly of the virus particles in the HIV-1 system. These noninfectious envelope-less particles revert readily to wild-type phenotype upon cotransfection with Env-producing plasmid DNAs.