Pathogenic Chikungunya Virus Evades B Cell Responses to Establish Persistence

Area of Science:

• Virology
• Immunology
• Musculoskeletal Diseases

Background:

• Chikungunya virus (CHIKV) and related alphaviruses cause significant musculoskeletal disease epidemics.
• Understanding CHIKV immune clearance failure is crucial for managing persistent infections.

Purpose of the Study:

• To investigate the mechanisms behind CHIKV immune clearance failure.
• To identify viral factors contributing to CHIKV persistence in joint tissues.

Main Methods:

• Comparative infection studies using attenuated (181/25) and pathogenic (AF15561) CHIKV strains in wild-type and B cell-deficient (μMT) mice.
• Mapping of viral mutations affecting clearance and neutralization.
• Assessment of antibody neutralization efficacy against different CHIKV strains and E2 glycoprotein domains.

Main Results:

• Viral persistence in joint tissues was observed with pathogenic CHIKV in wild-type mice and with the attenuated strain in B cell-deficient mice, indicating a role for antibodies in clearance.
• A conserved glycine at E2 glycoprotein position 82 was identified as a key factor impeding clearance and neutralization of multiple CHIKV strains.
• Antibodies targeting E2 domain B showed limited neutralization of pathogenic CHIKV strains, suggesting a mechanism for immune evasion.

Conclusions:

• Virus-specific antibodies are essential for the clearance of Chikungunya virus infection.
• Pathogenic CHIKV strains possess mechanisms, including evasion of E2 domain-B-neutralizing antibodies, to establish viral persistence in joint tissues.
• The E2 glycoprotein's conserved glycine at position 82 is a critical determinant for CHIKV immune evasion and persistence.