Interference of the Zika Virus E-Protein With the Membrane Attack Complex of the Complement System

Area of Science:

• Immunology
• Virology

Background:

• The complement system is crucial for clearing infections via mechanisms like opsonization and direct pathogen killing.
• Zika virus (ZIKV) activates the classical complement pathway, necessitating viral strategies to evade immune detection and clearance.

Purpose of the Study:

• To investigate how Zika virus (ZIKV) employs escape mechanisms to limit complement-mediated lysis.
• To identify specific viral components involved in interfering with the complement system's effector functions.

Main Methods:

• Enzyme-linked immunosorbent assay (ELISA) to detect binding of ZIKV E protein to terminal complement components.
• Western blot analysis to assess the impact of ZIKV E protein on C9 polymerization.
• Hemolytic assays using normal human serum (NHS) to evaluate complement-mediated lysis in the presence of ZIKV E protein or viral particles.

Main Results:

• ZIKV E protein binds to terminal complement pathway components (C5b6, C7, C8, C9).
• ZIKV E protein inhibits C9 polymerization, a key step in membrane attack complex (MAC) formation.
• The presence of ZIKV E protein or viral particles significantly reduces the hemolytic activity of NHS, indicating impaired complement-mediated lysis.

Conclusions:

• Zika virus (ZIKV) utilizes its envelope E protein to bind terminal complement proteins.
• This interaction interferes with membrane attack complex (MAC) formation, thereby inhibiting complement-mediated virolysis.
• ZIKV possesses an effective mechanism to evade clearance by the host complement system.