Changes in complement alternative pathway components, factor B and factor H during dengue virus infection in the...

Area of Science:

• Immunology
• Virology
• Complement System

Background:

• The complement alternative pathway (AP) is crucial in immune responses.
• Aberrant levels of factor B (FB) and factor H (FH) are linked to severe dengue in humans.
• Understanding the AP's role in dengue pathogenesis is vital.

Purpose of the Study:

• To investigate changes in FB and FH during dengue virus (DENV) infection in a mouse model.
• To evaluate the AG129 mouse model's utility for studying AP in severe dengue.
• To compare human and mouse AP component gene regulation.

Main Methods:

• Dengue virus infection in AG129 mice (IFN signaling-deficient).
• Quantification of FB and FH levels during viremia and terminal disease.
• Analysis of C3 degradation as a marker of complement activation.
• In silico promoter analysis of FB and FH genes in humans and mice.

Main Results:

• DENV infection altered FB and FH levels in AG129 mice, mirroring human severe dengue.
• Increased FB and decreased FH were observed during viremia, especially in antibody-dependent enhancement (ADE) models.
• Terminal disease showed decreased FB and FH with increased C3 degradation.
• Significant differences in promoter elements for FB and FH were found between humans and mice.

Conclusions:

• The AG129 mouse model demonstrates FB and FH changes associated with severe dengue, similar to humans.
• However, the model does not fully replicate human-specific, IFN-dependent regulation of FB and FH during DENV infection.
• The study highlights the limitations of the mouse model for exploring nuanced AP regulation in human dengue.