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Complementation of human immunodeficiency virus glycoprotein mutations in trans.
Y Morikawa1, J P Moore, E Fenouillet
1NERC Institute of Virology, Oxford, U.K.
The Journal of General Virology
|August 1, 1992
Summary
Researchers created hybrid glycoproteins to understand human immunodeficiency virus (HIV) CD4 binding. Complementation of mutant pairs revealed specific interactive sequences, offering a new target for disrupting HIV gp120 function.
Area of Science:
- Virology
- Structural Biology
- Immunology
Background:
- Human immunodeficiency virus type 1 (HIV-1) gp120 and HIV-2 gp105 glycoproteins bind the cellular receptor CD4.
- gp120 exhibits 10- to 20-fold higher affinity for CD4 than gp105, despite functional similarity.
Purpose of the Study:
- To investigate the structural requirements for CD4 binding in HIV-1 gp120 and HIV-2 gp105.
- To identify specific sequences crucial for receptor interaction and potential therapeutic targets.
Main Methods:
- Construction of hybrid glycoproteins by exchanging sequences between gp120 and gp105.
- Testing CD4 binding ability of mutant glycoproteins and their co-expressed pairs.
- Analysis of complementation data to determine interactive sequences.
Main Results:
- Hybrid glycoproteins with exchanged V1/V2 or V3 loops retained CD4 binding.
- Most other domain exchange mutants failed to bind CD4, indicating sequence-specific, long-range interactions.
- In vitro mixing did not restore CD4 binding, but co-expression led to complementation via heteromeric structures.
Conclusions:
- Specific interactive sequences within HIV glycoproteins are essential for CD4 receptor binding.
- These identified sequences represent a novel target for developing therapeutics to disrupt HIV gp120 function.