Redox-Triggered Infection by Disulfide-Shackled Human Immunodeficiency Virus Type 1 Pseudovirions
| Autor: | Dennis R. Burton, Cheryl Wiley, Charmagne Cayanan, Norbert Schülke, James M. Binley, William C. Olson |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Receptors
CCR5 viruses Immunology Mutant HIV Infections HIV Antibodies HIV Envelope Protein gp120 Biology Gp41 Membrane Fusion Microbiology Virus Cell Line Neutralization Tests Viral entry Virology Humans Disulfides Reporter gene Virion virus diseases Lipid bilayer fusion HIV Envelope Protein gp41 Transmembrane protein Virus-Cell Interactions Dithiothreitol Reducing Agents Insect Science HIV-1 biology.protein Antibody Oxidation-Reduction |
| Zdroj: | Journal of Virology. 77:5678-5684 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.77.10.5678-5684.2003 |
| Popis: | We previously described a human immunodeficiency virus type 1 (HIV-1) envelope mutant that introduces a disulfide bridge between the gp120 surface proteins and gp41 transmembrane proteins (J. M. Binley, R. W. Sanders, B. Clas, N. Schuelke, A. Master, Y. Guo, F. Kajumo, D. J. Anselma, P. J. Maddon, W. C. Olson, and J. P. Moore, J. Virol . 74: 627-643, 2000). Here we produced pseudovirions bearing the mutant envelope and a reporter gene to examine the mutant’s infectious properties. These pseudovirions attach to cells expressing CD4 and coreceptor but infect only when triggered with reducing agent, implying that gp120-gp41 dissociation is necessary for infection. Further studies suggested that virus entry was arrested after CD4 and coreceptor engagement. By measuring the activities of various entry inhibitors against the arrested intermediate, we found that gp120-targeting inhibitors typically act prior to virus attachment, whereas gp41 inhibitors are able to act postattachment. Unexpectedly, a significant fraction of antibodies in HIV-1-positive sera neutralized virus postattachment, suggesting that downstream fusion events and structures figure prominently in the host immune response. Overall, this disulfide-shackled virus is a unique tool with potential utility in vaccine design, drug discovery, and elucidation of the HIV-1 entry process. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|