Sp140L Is a Novel Herpesvirus Restriction Factor

Area of Science:

• Virology
• Immunology
• Genetics

Background:

• Herpesviruses, including Epstein-Barr Virus (EBV), must overcome host DNA sensing for infection.
• EBNA-LP, the first latency protein, is crucial for B cell transformation but its immune evasion role is unknown.

Purpose of the Study:

• To elucidate the role of EBNA-LP in evading host antiviral responses.
• To identify host restriction factors targeted by EBNA-LP.

Main Methods:

• Single-cell RNA sequencing of EBNA-LP-Knockout (LPKO) B cells infected with EBV.
• Genetic manipulation of SP100 and SP140L expression.
• Analysis of viral gene transcription and cellular proliferation.

Main Results:

• Speckled proteins, particularly SP100 and primate-specific SP140L, act as restriction factors against EBV.
• Loss of SP100 or SP140L reverses EBV restriction, suppresses interferon-stimulated genes, and restores viral transcription and proliferation.
• SP140L is also targeted by Herpesvirus Saimiri ORF3 protein, suggesting broader antiviral relevance.

Conclusions:

• EBNA-LP counters SP100 and SP140L to facilitate EBV infection.
• SP140L acts as a DNA sensing and transcriptional suppression factor in an IFN-independent innate immune response.
• This mechanism is likely important for infection by other nuclear DNA viruses.