A highly pathogenic simian/human immunodeficiency virus with genetic changes in cynomolgus monkey

Area of Science:

• Virology
• Immunology
• Primate Models

Background:

• Simian/human immunodeficiency virus (SHIV) is a model for human immunodeficiency virus (HIV) research.
• Understanding SHIV pathogenicity is crucial for developing effective HIV therapies.

Purpose of the Study:

• To characterize a highly pathogenic SHIV strain (SHIV-C2/1) in cynomolgus monkeys.
• To investigate the relationship between antibody response and SHIV pathogenicity.

Main Methods:

• Infection of cynomolgus monkeys with SHIV-C2/1, p-SHIV, or SHIV-MN.
• Monitoring of CD4+ lymphocyte counts, viral load, and antibody responses (anti-Gag, anti-Env).
• Genetic sequencing of SHIV env and Nef genes.

Main Results:

• SHIV-C2/1 induced rapid CD4+ depletion, diarrhea, and intense viremia within one week.
• Anti-Gag antibody response was absent in SHIV-C2/1 infected animals, unlike p-SHIV or SHIV-MN infections.
• Conserved genetic changes were identified in Env (C2, V3, gp41) and Nef proteins of pathogenic SHIV-C strains.

Conclusions:

• The SHIV-C2/1-monkey model demonstrates rapid and severe pathogenicity.
• Absence of anti-Gag antibody response may be associated with SHIV pathogenicity.
• In vivo genetic alterations during serum passage contribute to SHIV virulence.