PML Body Component Sp100A Restricts Wild-Type Herpes Simplex Virus 1 Infection

Area of Science:

• Virology
• Immunology
• Cell Biology

Background:

• Sp100 (speckled protein 100 kDa) is a nuclear protein involved in immunity.
• Sp100 isoforms regulate cellular and viral genes.
• Herpes simplex virus 1 (HSV-1) protein ICP0 targets Sp100, complicating studies of Sp100's role in natural infection.

Purpose of the Study:

• To investigate the antiviral activity of Sp100 isoforms against wild-type HSV-1.
• To elucidate the molecular behavior and localization of Sp100 during HSV-1 infection.
• To explore the role of extracellular Sp100 in antiviral defense.

Main Methods:

• Infection of various cell lines (HEp-2, Sp100-/-, PML-/-) with wild-type HSV-1.
• Analysis of Sp100 localization (nuclear vs. cytoplasmic) and levels during infection.
• Detection of Sp100 in extracellular vesicles (EVs) and its association with EVs.
• Correlation of Sp100A levels with EV secretion and antiviral potency.

Main Results:

• Sp100 isoform A (Sp100A) inhibited wild-type HSV-1 propagation.
• Nuclear Sp100 decreased during infection due to ICP0, while cytoplasmic Sp100 remained stable.
• Sp100 was secreted and associated with EVs, not virions.
• EV-associated Sp100A restricted HSV-1 in recipient cells.

Conclusions:

• Sp100A exhibits potent, independent antiviral activity against wild-type HSV-1.
• Cytoplasmic Sp100 is secreted via EVs, representing a novel antiviral mechanism.
• Extracellular Sp100, particularly Sp100A within EVs, contributes to host defense against HSV-1 through intercellular communication.