Complement Suppresses the Initial Type 1 Interferon Response to Ocular Herpes Simplex Virus Type 1 Infection in Mice

Area of Science:

• Immunology
• Virology
• Ophthalmology

Background:

• The complement system (CS) is crucial for pathogen defense and clearing cellular debris.
• Previous studies showed C3KO mice had reduced survival and higher viral loads after ocular HSV-1 infection.

Purpose of the Study:

• To investigate the impact of complement deficiency on early viral replication and inflammation in the cornea following HSV-1 infection.
• To determine if complement deficiency affects myeloid cell populations and cytokine/chemokine profiles in the cornea.

Main Methods:

• Comparison of infectious virus levels and HSV-1 lytic gene expression in C3KO and WT mice at early time points post-infection (12 and 24 h pi).
• Flow cytometry analysis of myeloid cell populations (macrophages, neutrophils) in the cornea.
• Cytokine and chemokine analysis in corneal tissue using multiplex assays.
• Gene expression analysis of type I interferons (IFN-α1, IFN-β) and downstream effectors (tetherin, RNase L).

Main Results:

• C3KO mice exhibited significantly less infectious virus and reduced HSV-1 lytic gene expression in the cornea at 24 h pi.
• No significant differences were observed in corneal myeloid cell populations between WT and C3KO mice at 24 h pi.
• CCL3 (MIP-1α) levels were significantly higher in WT mice at 12 h pi, while C3KO mice showed increased expression of type I IFN genes and downstream antiviral effectors.

Conclusions:

• Early complement activation appears to interfere with the induction of the type I interferon response during ocular HSV-1 infection.
• Complement deficiency leads to enhanced early type I interferon signaling, contributing to resistance against HSV-1 in the cornea.
• These findings highlight a complex interplay between the complement system and innate antiviral immunity in the early stages of ocular viral infections.