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Changes in HIV-1 Capsid Stability Induced by Common Cytotoxic-T-Lymphocyte-Driven Viral Sequence Mutations.
P Schommers1,2,3, G Martrus1, U Matschl1
1Department of Virus Immunology, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
Journal of Virology
|June 10, 2016
Summary
Cytotoxic T-lymphocyte (CTL) escape mutations in HIV-1 p24 Gag, driven by protective HLA alleles, impact capsid stability. These mutations may explain persistent viral control despite immune escape.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Individuals with protective HLA class I alleles show better HIV-1 control, linked to cytotoxic T-lymphocyte (CTL) responses.
- CTL escape mutations in HIV-1 p24 Gag are associated with reduced viral replication capacity.
- The exact mechanisms behind reduced viral fitness due to these mutations are not fully understood.
Purpose of the Study:
- To investigate the impact of specific CTL-associated p24 Gag mutations on HIV-1 capsid stability.
- To explore the relationship between capsid stability, viral infectivity, and immune escape.
Main Methods:
- Assessed HIV-1 capsid stability using a cyclosporine (CsA) washout assay.
- Analyzed the effects of specific CTL escape mutations (T242N, R264K) and compensatory mutations (L268M, S173A) in p24 Gag.
- Correlated capsid stability with viral infectivity.
Main Results:
- HLA-B57- and HLA-B27-associated CTL escape mutations (T242N, R264K) delayed HIV-1 capsid uncoating, indicating altered stability.
- Compensatory mutations (L268M, S173A) restored capsid uncoating kinetics.
- Increased capsid stability correlated with reduced viral infectivity.
Conclusions:
- CTL-driven escape mutations in HIV-1 p24 Gag significantly impact capsid stability.
- Altered capsid stability, influenced by immune escape mutations, may contribute to persistent control of viral replication.
- These findings provide a mechanism for reduced viral fitness associated with CTL escape variants.
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