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Updated: Sep 2, 2025
18:10
Isolation of Fidelity Variants of RNA Viruses and Characterization of Virus Mutation Frequency
Published on: June 16, 2011
29.7K
Host translesion polymerases are required for viral genome integrity
Sebastian Zeltzer1, Pierce Longmire2,3, Marek Svoboda4
1BIO5 Institute, University of Arizona, Tucson, AZ 85721.
Summary
Human cytomegalovirus (HCMV) infection relies on host translesion synthesis (TLS) DNA polymerases. While some TLS polymerases restrict viral genome synthesis, others like polymerase ζ are essential for replication and stability.
Area of Science:
- Molecular Biology
- Virology
- Genetics
Background:
- Human cells possess numerous DNA polymerases for genome maintenance.
- DNA viruses, like herpesviridae, encode fewer polymerases, suggesting reliance on host factors.
- Translesion synthesis (TLS) polymerases are crucial for DNA repair and bypassing lesions.
Purpose of the Study:
- To investigate the role of host Y-family TLS DNA polymerases in human cytomegalovirus (HCMV) replication.
- To determine how TLS polymerases influence viral genome synthesis and stability.
Main Methods:
- Depletion of specific Y-family TLS polymerases in human cells.
- Assessing the impact on HCMV genome synthesis and replication efficiency.
- Analyzing viral genome rearrangements using sequencing.
Main Results:
- Most Y-family TLS polymerases inhibited HCMV genome synthesis and replication.
- Polymerase ζ complex was required for optimal HCMV genome synthesis and replication.
- TLS polymerases suppressed viral genome rearrangements, especially at GC-rich and repeat regions.
- Host TLS polymerases also impacted herpes simplex virus type 1 replication.
Conclusions:
- Host TLS polymerases play a dual role in HCMV infection, with some restricting and others promoting replication.
- TLS polymerases are critical for maintaining viral genome stability by suppressing rearrangements.
- These findings suggest a broader role for host DNA polymerases in the replication of DNA viruses.
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