Newly Exerted T Cell Pressures on Mutated Epitopes following Transmission Help Maintain Consensus HIV-1 Sequences

Area of Science:

• Immunology
• Virology
• Genetics

Background:

• CD8+ T cells play a dual role in HIV-1 infection, aiding viral control while driving sequence evolution through escape mutations.
• Cytotoxic T lymphocyte (CTL) escape mutations are common, but the role of T cell pressure in reverting HIV-1 to consensus sequences is less understood.

Purpose of the Study:

• To investigate the frequency of transmitted HIV-1 mutations reverting to consensus sequences.
• To determine the association between these reversions and T cell responses to the mutated epitopes.

Main Methods:

• Analysis of 14 HIV-1 transmission pairs (source and recipient).
• Identification and sequencing of mutations in HIV-1 gag regions (p17, p24, p2, p7).
• Assessment of T cell responses to mutated and reverted epitopes using synthesized peptides.

Main Results:

• Transmitted mutations were frequent, with an average of 17% of mutated epitopes reverting to consensus in recipients.
• T cell responses to mutated epitopes were detected in 7 out of 14 recipients experiencing reversion.
• Transmitted non-consensus epitopes were immunogenic in HLA-mismatched recipients.

Conclusions:

• New T cell pressure following transmission significantly contributes to maintaining consensus HIV-1 sequences.
• Transmitted mutations are often immunogenic, highlighting the dynamic interplay between HIV-1 evolution and host immune response.