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07:06
Prediction of HIV-1 Coreceptor Usage (Tropism) by Sequence Analysis using a Genotypic Approach
Published on: December 1, 2011
Vpr is preferentially targeted by CTL during HIV-1 infection
M Altfeld1, M M Addo, R L Eldridge
1Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|August 18, 2001
Summary
Cytotoxic T lymphocyte (CTL) responses frequently target HIV-1 Vpr and Vif proteins during natural infection. These findings are crucial for understanding HIV immunity and designing effective vaccines.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- HIV-1 accessory proteins Vpr, Vpu, and Vif are vital for viral replication.
- Their cytoplasmic production implies processing for cytotoxic T lymphocyte (CTL) recognition.
- The specific CTL epitopes and targeting extent in natural HIV-1 infection are not well-defined.
Purpose of the Study:
- To analyze CTL responses against HIV-1 Vpr, Vpu, and Vif proteins in infected individuals.
- To identify precise CTL epitopes within these accessory proteins.
- To evaluate the contribution of these proteins to the overall HIV-1-specific CD8(+) T cell response.
Main Methods:
- Analysis of CTL responses in 60 HIV-1-infected individuals and 10 controls.
- Use of overlapping peptides spanning Vpr, Vpu, and Vif.
- Measurement of IFN-gamma production via ELISPOT and intracellular cytokine staining.
- Confirmation of HLA class I restriction and cytotoxic activity using CD8(+) T cell lines.
Main Results:
- CD8(+) T cell responses were detected against Vpr (45%), Vpu (2%), and Vif (33%) of infected individuals.
- Multiple CTL epitopes were identified in functionally significant regions of Vpr and Vif.
- Vpr and p17 were the most targeted proteins per unit length by CD8(+) T cells.
Conclusions:
- HIV-1 Vif and Vpr are frequently targeted by CTLs during natural infection.
- These proteins significantly contribute to the total HIV-1-specific CD8(+) T cell response.
- Findings are important for assessing immune responses and designing HIV vaccines.
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