This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Steffy, K R Articles by Wong-Staal, F Search for Related Content PubMed PubMed Citation Articles by Steffy, K R Articles by Wong-Staal, F

Transdominant inhibition of wild-type human immunodeficiency virus type 2 replication by an envelope deletion mutant.

Department of Medicine, University of California San Diego, La Jolla 92093-0665.

ABSTRACT

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.

This article has been cited by other articles:

• Miklossy, G., Tozser, J., Kadas, J., Ishima, R., Louis, J. M., Bagossi, P. (2008). Novel macromolecular inhibitors of human immunodeficiency virus-1 protease. Protein Eng Des Sel 21: 453-461 [Abstract] [Full Text]  
• Chen, S. S.-L., Lee, S.-F., Chuang, C.-K., Raj, V. S. (1999). trans-Dominant Interference with Human Immunodeficiency Virus Type 1 Replication and Transmission in CD4+ Cells by an Envelope Double Mutant. J. Virol. 73: 8290-8302 [Abstract] [Full Text]  
• Chen, S. S.-L., Lee, S.-F., Hao, H.-J., Chuang, C.-K. (1998). Mutations in the Leucine Zipper-Like Heptad Repeat Sequence of Human Immunodeficiency Virus Type 1 gp41 Dominantly Interfere with Wild-Type Virus Infectivity. J. Virol. 72: 4765-4774 [Abstract] [Full Text]  
• D'Aloja, P., Olivetta, E., Bona, R., Nappi, F., Pedacchia, D., Pugliese, K., Ferrari, G., Verani, P., Federico, M. (1998). gag, vif, and nef Genes Contribute to the Homologous Viral Interference Induced by a Nonproducer Human Immunodeficiency Virus Type 1 (HIV-1) Variant: Identification of Novel HIV-1-Inhibiting Viral Protein Mutants. J. Virol. 72: 4308-4319 [Abstract] [Full Text]  
• Johnston, M., Hoth, D. (1993). Present status and future prospects for HIV therapies. Science 260: 1286-1293 [Abstract]