Association between gp120 envelope V1V2 and V4V5 variable loop profiles in a defined HIV-1 transmission cluster

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• The gp120 Env variable loop sequences of HIV-1 are known to change during infection and influence viral phenotypes.
• Understanding these sequence variations is crucial for developing effective HIV-1 vaccines and treatments.

Purpose of the Study:

• To investigate signature sequence differences in the HIV-1 gp120 Env between acute and chronic infection stages.
• To analyze sequence variations within a transmission cluster of closely related HIV-1 viruses.

Main Methods:

• Sequencing of multiple HIV-1 gp120 Env clones from 11 individuals (6 acute, 5 chronic infection).
• Comparative analysis of predicted amino acid sequences and potential N-linked glycosylation site (PNGS) densities.
• Validation using sequences from the Los Alamos HIV sequence database.

Main Results:

• Acute infection viruses exhibited lower PNGS densities and a higher amino acid length/PNGS ratio compared to chronic infection viruses.
• A negative correlation between V1V2 and V4V5 regions in amino acid length and PNGS numbers was observed during HIV-1 transmission, which was lost post-seroconversion.
• These findings were corroborated by analysis of large sequence datasets categorized by transmission timing.

Conclusions:

• A structural association between gp120 V1V2 and V4V5 regions exists during HIV-1 transmission but is disrupted post-seroconversion.
• These structural insights are important for designing HIV-1 immunogens to elicit protective antibody responses against transmitted viruses.