Transdominant inhibition of wild-type human immunodeficiency virus type 2 replication by an envelope deletion mutant.
The envelope glycoprotein of human immunodeficiency virus type 2 (HIV-2) is primarily responsible for virus attachment and entry into the target cell population. We constructed an HIV-2 mutant virus containing an in-frame deletion within the putative CD4-binding sequences of the envelope glycoprotein and confirmed that the mutant envelope is unable to bind CD4 and that the mutant virus is noninfectious. To investigate whether this mutant could dominantly interfere with wild-type replication, we coexpressed proviral DNAs of both wild-type and mutant viruses in cells and assayed the production of infectious HIV-2 virions. Interference with virus replication was indeed observed with mutant DNA, and a maximal effect was achieved with 10-fold excess mutant DNA over wild-type DNA in the cotransfection experiments. The transdominant effect on virus replication does not appear to be at the level of wild-type envelope expression or gp120-CD4 interaction. Rather, the interference may be at the level of mixed-oligomer formation during progeny virus assembly and may occur by either destabilizing the multimeric structure of gp120 or forming a defective mixed multimeric gp120 which is unable to complete the receptor binding and/or postbinding events needed for infection.
Steffy
K R
KR
Department of Medicine, University of California San Diego, La Jolla 92093-0665.
Wong-Staal
F
F
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015704:CD4 Antigens / Q000378:metabolism; D002460:Cell Line; D002522:Chlorocebus aethiops; D015967:Gene Expression Regulation, Viral; D015683:Gene Products, gag / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000502:physiology*; D015498:HIV-2 / Q000254:growth & development* / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D017384:Sequence Deletion; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014779:Virus Replication
D015704:CD4 Antigens; D015683:Gene Products, gag; D015699:HIV Envelope Protein gp120; D014759:Viral Envelope Proteins