Relationship between Functional Profile of HIV-1 Specific CD8 T Cells and Epitope Variability with the Selection of Escape Mutants in Acute HIV-1 Infection
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Discussion
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Implication
Cohort study reveals total CD8+ T-cell magnitude and epitope entropy drive viral escape in acute HIV-1, suggesting immune pressure extends beyond multifunctional cytotoxicity.
Key Points
- To evaluate whether CD8+ T-cell multifunctionality and epitope variability drive the selection of viral escape mutants during acute and early HIV-1 infection.
- Studied 7 antiretroviral therapy-naïve individuals longitudinally between 1 and 87 weeks following symptom onset of acute HIV-1 infection.
- Assessed the functionality of HIV-1-specific memory CD8+ T cells via multiparameter flow cytometry using synthetic peptides corresponding to autologous transmitted/founder viral sequences.
- Early CD8+ T-cell responses were primarily oligofunctional, with multifunctionality increasing over time; however, only overall response magnitude, not polyfunctionality, significantly associated with escape mutant selection.
- High frequencies of MIP-1β-producing CD8+ T cells were observed, indicating that non-cytotoxic immune mechanisms contribute to selective pressure during acute infection.
- Epitope entropy, representing population-level sequence diversity and mutational tolerance, correlated significantly with the rate of viral escape mutant emergence.
Cite This Study
Ferrari et al. (2011) studied this question.