Innate and acquired immunity to herpes simplex virus type 1

Area of Science:

• Immunology
• Virology
• Neuroscience

Background:

• Herpes simplex virus type 1 (HSV-1) can establish latent infections in the trigeminal ganglion (TG) after ocular infection.
• Understanding mechanisms to prevent HSV-1 central nervous system (CNS) invasion is crucial for managing neurological complications.

Purpose of the Study:

• To investigate the protective effects of pre-infection immunization against HSV-1 ocular infection and subsequent nervous system invasion.
• To elucidate the roles of antibody responses and interferons (IFNs) in mediating this protection.

Main Methods:

• Mice were immunized with heat-inactivated HSV-1 or unrelated antigens prior to ocular HSV-1 infection.
• Viral replication, latency-associated transcripts, and immune gene expression (IFN-γ, CD8, IL-12, TNF-α) in the eye and TG were assessed.
• Neutralizing antibodies against IFN-α/β and IFN-γ were used to evaluate their roles in protection.

Main Results:

• Pre-infection immunization significantly reduced latent HSV-1 infection in the TG and prevented spread to the cerebellum.
• This protection correlated with reduced IFN-γ mRNA in the TG and the presence of serum antibodies to HSV-1.
• Treatment with anti-IFN-α/β antibodies increased viral replication and load in the TG, indicating a crucial role for IFN-α/β in limiting neuroinvasion.

Conclusions:

• Exposure to viral antigens shortly before infection is critical in limiting HSV-1 spread to the nervous system.
• Both antibody-mediated immunity and type I interferons (IFN-α/β) are essential for preventing peripheral HSV-1 infection from reaching the CNS.