Herpes simplex virus 1 infected neuronal and skin cells differ in their susceptibility to complement attack

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Herpes simplex virus type 1 (HSV-1) establishes lifelong, typically asymptomatic, latent infections in neurons.
• Reactivation causes skin blistering, while neurons remain largely unaffected, a phenomenon not fully understood.

Purpose of the Study:

• To investigate differences in complement attack control between neuronal and skin cells during HSV-1 infection.
• To determine if cellular complement regulation mechanisms explain neuronal cell survival during HSV-1 infection.

Main Methods:

• In vitro infection of human embryonal skin (HES) cells and neuronal Paju cells with HSV-1.
• Analysis of complement activation and membrane attack complex (MAC) deposition.
• Quantification of complement regulator expression (DAF, CD59) over time.

Main Results:

• Both HES and Paju cells initially resisted MAC deposition after HSV-1 infection.
• Complement regulators DAF and CD59 expression increased in both cell types early in infection.
• Infected HES cells lost complement control by 12 hours, showing decreased regulator expression and increased MAC deposition.
• Neuronal Paju cells maintained complement regulator expression, limiting MAC deposition to 10% at 12 hours.

Conclusions:

• HSV-1 infected neuronal cells exhibit superior defense against complement attack compared to infected skin cells.
• Enhanced complement regulation in neurons may facilitate the persistence of latent HSV-1 infections.
• These findings offer insights into the differential cellular responses to HSV-1 and the mechanisms of viral latency.