Distinct pathogenic sequela in rhesus macaques infected with CCR5 or CXCR4 utilizing SHIVs

Area of Science:

• Virology
• Immunology
• Pathogenesis Research

Background:

• Simian-human immunodeficiency virus (SHIV) infection in macaques serves as a crucial in vivo model for studying human immunodeficiency virus type 1 (HIV-1) pathogenesis.
• Understanding the role of the HIV-1 envelope protein and viral co-receptor usage is vital for developing effective vaccines and therapeutics.

Purpose of the Study:

• To compare the pathogenic outcomes of infection with CCR5 (R5)-specific SHIVSF162P and CXCR4 (X4)-specific SHIVSF33A.2 in macaques.
• To elucidate the influence of viral co-receptor tropism on CD4+ T cell depletion in both intestinal and peripheral compartments.

Main Methods:

• Infection of macaques with two distinct SHIV strains: SHIVSF162P (R5-tropic) and SHIVSF33A.2 (X4-tropic).
• Monitoring viral replication levels and assessing CD4+ T cell populations in both intestinal and peripheral tissues.
• Comparative analysis of pathogenic outcomes based on co-receptor utilization.

Main Results:

• Both R5 and X4 SHIV infections demonstrated comparable viral replication levels.
• SHIVSF162P (R5) infection led to significant intestinal CD4+ T cell loss, followed by peripheral depletion.
• SHIVSF33A.2 (X4) infection caused profound peripheral CD4+ T cell loss without a similar intestinal impact.

Conclusions:

• Co-receptor utilization (CCR5 vs. CXCR4) critically influences HIV-1 pathogenesis and CD4+ T cell tropism.
• This SHIV macaque model effectively recapitulates distinct pathogenic profiles relevant to HIV-1 envelope protein function.
• The findings support the utility of this model for preclinical evaluation of HIV-1 vaccines and therapies targeting the envelope protein.