Neutralization Sensitivity of HIV-1 CRF07_BC From an Untreated Patient With a Focus on Evolution Over Time

Area of Science:

• Virology
• Immunology
• Infectious Diseases

Background:

• HIV-1 envelope (Env) diversity impacts broadly neutralizing antibody (bNAb) efficacy.
• bNAbs offer a promising alternative for HIV-1 prevention and treatment.
• Characterizing viral evolution aids in designing immunogens and therapeutic antibodies.

Purpose of the Study:

• To characterize viral evolution in a long-term non-progressor with HIV-1 CRF07_BC infection.
• To monitor changes in neutralizing activity and sensitivity over time.
• To identify mutations associated with bNAb resistance for improved immunogen design.

Main Methods:

• Sequencing of 59 full-length Env gene fragments from sequential plasma samples (2016-2020).
• Generation of 24 functional Env-pseudotyped viruses.
• Assessment of viral sensitivity to autologous plasma and a panel of bNAbs.

Main Results:

• Potential N-linked glycosylation sites in V1 and V5 increased over time.
• Later-time viruses showed increased resistance to autologous plasma and some bNAbs (10E8, VRC01, 12A21).
• All viruses were resistant to bNAbs 2G12, PGT121, and PGT135; mutations F277W and S465T were associated with increased bNAb resistance.

Conclusions:

• HIV-1 evolution in long-term non-progressors can lead to immune escape from bNAbs.
• Identifying resistance-associated mutations (e.g., S465T) is vital for developing next-generation HIV-1 therapies.
• Understanding viral dynamics informs strategies for effective HIV-1 prevention and treatment.