TRPC1 participates in the HSV-1 infection process by facilitating viral entry

Area of Science:

• Cell biology
• Virology
• Immunology

Background:

• Mammalian transient receptor potential (TRP) channels are key regulators of calcium (Ca2+) signaling.
• These channels influence numerous physiological processes.
• Herpes simplex virus type 1 (HSV-1) is a common human pathogen.

Purpose of the Study:

• To investigate the specific role of TRPC1 in HSV-1 entry and infection.
• To explore the molecular mechanisms underlying TRPC1's involvement in viral entry.
• To evaluate TRPC1 as a potential therapeutic target for HSV-1.

Main Methods:

• Investigated HSV-1 entry and Ca2+ flux in cells with varying TRPC1 expression.
• Utilized protein interaction assays to identify HSV-1 components interacting with TRPC1.
• Employed knockout mouse models (TRPC1-/-) to assess in vivo effects of HSV-1 infection.
• Analyzed clinical buccal biopsy samples from HSV-1 infected patients.

Main Results:

• HSV-1 entry and associated Ca2+ flux were dependent on Orai1, STIM1, and TRPC1.
• Inhibiting Ca2+ entry or reducing TRPC1 levels significantly decreased viral entry and infection.
• HSV-1 glycoprotein D directly interacted with TRPC1, enhancing viral entry.
• TRPC1 knockout mice exhibited reduced ocular abnormalities and morbidity following HSV-1 infection.
• A strong correlation was observed between HSV-1 infection and TRPC1 localization at the plasma membrane in patient samples.

Conclusions:

• TRPC1 plays a critical role in facilitating HSV-1 entry into host cells.
• The interaction between HSV-1 glycoprotein D and TRPC1 is essential for efficient viral entry.
• TRPC1 is a promising therapeutic target for developing novel anti-HSV treatments.