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Updated: Dec 24, 2025
11:28
Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus
Published on: October 7, 2011
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Human cytomegalovirus long noncoding RNA4.9 regulates viral DNA replication
Julie Tai-Schmiedel1, Sharon Karniely2, Betty Lau3
1Weizmann Institute of Science, Department of Molecular Genetics, Rehovot, Israel.
Plos Pathogens
|April 16, 2020
Summary
Human cytomegalovirus (HCMV) encodes a long noncoding RNA (lncRNA) called RNA4.9. This RNA is crucial for viral DNA replication and growth, potentially by forming an R-loop at the origin of replication.
Area of Science:
- Virology
- Molecular Biology
- Genetics
Background:
- Human cytomegalovirus (HCMV) possesses a compact genome, yet encodes four long noncoding RNAs (lncRNAs).
- The functions of these HCMV-encoded lncRNAs, despite accumulating during lytic infection, are largely uncharacterized.
Purpose of the Study:
- To investigate the function of HCMV-encoded lncRNA4.9 during viral infection.
- To elucidate the role of lncRNA4.9 in viral DNA replication and replication compartment formation.
Main Methods:
- Depletion of lncRNA4.9 to assess its impact on viral replication.
- Localization studies of lncRNA4.9 within the viral replication compartment.
- CRISPR-Cas9 targeting of the lncRNA4.9 promoter and genetic relocalization of the origin of replication (oriLyt).
Main Results:
- Depletion of lncRNA4.9 significantly restricted HCMV DNA replication and viral growth.
- lncRNA4.9 localizes to the viral nuclear replication compartment and forms an RNA-DNA hybrid (R-loop) at the oriLyt.
- Targeting the RNA4.9 promoter or relocating oriLyt reduced single-stranded DNA-binding protein (ssDBP) levels, indicating coupling to oriLyt activity.
- A similar lncRNA was identified in murine cytomegalovirus (MCMV).
Conclusions:
- HCMV lncRNA4.9 is essential for regulating viral DNA replication and viral growth.
- Viral ssDBP levels are intrinsically linked to oriLyt activity.
- The identified regulatory mechanisms involving lncRNAs and oriLyt activity may be conserved across betaherpesviruses.
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