Complement Opsonization Promotes Herpes Simplex Virus 2 Infection of Human Dendritic Cells

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Herpes simplex virus 2 (HSV-2) is a prevalent global sexually transmitted infection.
• HSV-2 virions in genital fluids are coated with complement proteins and antibodies, influencing immune responses.
• Dendritic cells (DCs) are key immune cells that activate antiviral responses against HSV-2.

Purpose of the Study:

• To investigate the impact of complement and antibody opsonization on HSV-2 infection of immature dendritic cells (DCs).
• To examine how opsonization affects DCs' inflammatory and antiviral response capabilities.
• To understand HSV-2 pathogenesis under in vivo-like conditions.

Main Methods:

• Immature DCs were infected with HSV-2 opsonized with complement alone or with complement and antibodies.
• Analysis of DC infection, new infectious viral particle production, and inflammatory/antiviral cytokine secretion.
• Investigation of the roles of complement cascade activation, complement receptor 3, and endocytosis in DC infection.

Main Results:

• Complement opsonization of HSV-2 significantly enhanced DC infection and the production of infectious viral particles.
• This enhancement was dependent on complement cascade activation and functional complement receptor 3.
• The presence of both complement and HSV-specific antibodies largely abolished HSV-2 infection of DCs.

Conclusions:

• Opsonization conditions in vivo, involving complement and antibodies, critically shape HSV-2 infection dynamics in DCs.
• Complement enhances HSV-2 infectivity in DCs, while antibodies counteract this effect.
• Studying HSV-2 under physiological conditions is crucial for understanding its pathogenesis and immune evasion strategies.