Human Herpes Simplex Virus-1 depletes APOBEC3A from nuclei.

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• The APOBEC3 (APOBEC3A) family of DNA-cytosine deaminases plays a vital role in innate immunity by inactivating and mutating various human viruses.
• Understanding the cellular localization and regulation of APOBEC3A during viral infection is critical for comprehending host-pathogen interactions.

Purpose of the Study:

• To investigate the subcellular localization dynamics of APOBEC3A in response to Herpes Simplex Virus-1 (HSV-1) infection.
• To identify viral factors responsible for modulating APOBEC3A localization.

Main Methods:

• Construction of a human cell line inducibly expressing EGFP-tagged APOBEC3A.
• Infection of engineered cells with HSV-1 and monitoring of viral titer and APOBEC3A localization over time.
• Investigating the role of the HSV-1 UL39 gene in APOBEC3A exclusion from the nucleus.

Main Results:

• APOBEC3A was predominantly nuclear in uninfected cells but translocated to the cytoplasm by 12 hours post-HSV-1 infection.
• HSV-1 replication and viral titer were not significantly affected by APOBEC3A expression.
• The HSV-1 UL39 gene product, encoding a subunit of viral ribonucleotide reductase, was sufficient to induce APOBEC3A cytoplasmic relocalization.
• HSV-1 UL39 demonstrated a more potent exclusion of APOBEC3A from the nucleus compared to Epstein Barr virus's BORF2 on APOBEC3B.

Conclusions:

• Herpes Simplex Virus-1 actively manipulates APOBEC3A localization, moving it from the nucleus to the cytoplasm.
• The viral UL39 gene product is a key factor in mediating this nuclear exclusion, representing a viral evasion strategy.
• APOBEC3A's antiviral activity may be hindered by this virus-induced relocalization, impacting host defense mechanisms.