Protective immune responses against West Nile virus are primed by distinct complement activation pathways

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• West Nile virus (WNV) can cause severe central nervous system infections in vertebrates, including humans.
• Previous research indicates the complement system's critical role in controlling WNV infection.

Purpose of the Study:

• To investigate the specific contributions of individual complement activation pathways (classical, lectin, alternative) in protection against WNV disease.
• To understand how these pathways influence viral spread and host immune responses.

Main Methods:

• Utilized genetically modified mice deficient in specific complement components (C1q, C4, factor B, factor D).
• Assessed WNV-induced mortality, viral dissemination, and adaptive immune cell (B and T cell) responses in these deficient models.

Main Results:

• Genetic deficiencies in C1q, C4, factor B, or factor D led to increased WNV-related mortality.
• Absence of alternative pathway activation accelerated WNV dissemination to the CNS and reduced CD8+ T cell responses.
• Lack of classical and lectin pathways impaired both B and T cell responses to WNV.
• C1q deficiency specifically impacted splenic WNV infection but not adaptive immune development.

Conclusions:

• All complement activation pathways collectively limit WNV spread and disease.
• Distinct complement pathways differentially prime adaptive immune responses, influencing WNV control.
• Understanding these pathway-specific roles is vital for developing targeted WNV therapeutics.