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Immunophilins and HIV-1 infection
D Minder1, J Böni, J Schüpbach
1Institute of Biochemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
Archives of Virology
|August 16, 2002
Summary
Exogenous immunophilins do not affect HIV-1 infection. However, cyclophilin A (CypA) plays a role after reverse transcription, likely during capsid formation, impacting viral maturation.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- HIV-1 envelope glycoprotein gp120 V3 loop peptides bind to immunophilins cyclophilin A (CypA), CypB, and FKBP12.
- Immunophilins are investigated for their potential role in HIV-1 infection due to their binding affinity to gp120.
Purpose of the Study:
- To investigate whether immunophilins affect HIV-1 infection.
- To determine the stage at which CypA influences HIV-1 replication.
Main Methods:
- Infection of T cells and PBMCs with HIV-1 strains in the presence of varying immunophilin concentrations.
- P24 antigen ELISA and real-time PCR to measure viral infection.
- Treatment with cyclosporin A (CsA) to block CypA function and assess its impact on infection.
Main Results:
- Exogenously added immunophilins did not influence HIV-1 infection rates.
- Cyclosporin A treatment decreased infectious virus yield, but proviral DNA production was normal in the first round.
- Pre-treatment of HIV-1 inocula with CsA did not inhibit infection, suggesting CypA acts endogenously after reverse transcription.
Conclusions:
- Endogenous cyclophilin A (CypA) is crucial for HIV-1 replication post-reverse transcription and pre-maturation, likely during capsid formation.
- FK520, an FKBP-binding immunosuppressor, showed no effect on HIV-1 infection.