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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
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Complex roles for proliferating cell nuclear antigen in restricting human cytomegalovirus replication
Pierce Longmire1,2,3, Olivia Daigle4,5, Sebastian Zeltzer3
1Graduate Program in Molecular Medicine, University of Arizona, Tucson, Arizona, USA.
Biorxiv : the Preprint Server for Biology
|January 20, 2025
Summary
Human cytomegalovirus (HCMV) infection recruits proliferating cell nuclear antigen (PCNA) and translesion synthesis (TLS) polymerases. PCNA restricts HCMV replication, with distinct roles in viral genome stability and diversity.
Area of Science:
- Virology
- Molecular Biology
- DNA Repair
Background:
- DNA viruses hijack host DNA repair pathways for replication.
- Human cytomegalovirus (HCMV) utilizes host factors like proliferating cell nuclear antigen (PCNA) and translesion synthesis (TLS) polymerases for viral DNA (vDNA) synthesis.
- The precise role of PCNA in HCMV infection is not fully understood.
Purpose of the Study:
- To investigate the role of PCNA and its modifications in HCMV replication and viral genome integrity.
- To elucidate the distinct functions of PCNA and TLS polymerases in viral DNA synthesis.
Main Methods:
- Monitoring PCNA modification levels (monoubiquitination and SUMOylation) during HCMV infection.
- Assessing the impact of PCNA modification at lysine 164 (K164) on viral replication.
- Analyzing viral genome integrity and diversity (SNVs, novel junctions, rearrangements) in the presence and absence of PCNA modification.
Main Results:
- Monoubiquitinated PCNA (mUb-PCNA) levels increase during HCMV infection.
- Modification at K164 is crucial for PCNA-mediated restriction of viral replication.
- PCNA promotes single nucleotide variants (SNVs) in vDNA, independent of K164 modification, but is not required for preventing large-scale rearrangements.
Conclusions:
- PCNA acts as a multifaceted restriction factor against HCMV infection.
- PCNA exhibits separable functions in regulating viral genome stability and diversity.
- These findings suggest novel roles for TLS polymerases beyond canonical translesion synthesis in host biology and viral infections.
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