Adeno-associated virus type 2 modulates the host DNA damage response induced by herpes simplex virus 1 during coinfection
- PMID: 22013059
- PMCID: PMC3255894
- DOI: 10.1128/JVI.05694-11
Adeno-associated virus type 2 modulates the host DNA damage response induced by herpes simplex virus 1 during coinfection
Abstract
Adeno-associated virus type 2 (AAV2) is a human parvovirus that relies on a helper virus for efficient replication. Herpes simplex virus 1 (HSV-1) supplies helper functions and changes the environment of the cell to promote AAV2 replication. In this study, we examined the accumulation of cellular replication and repair proteins at viral replication compartments (RCs) and the influence of replicating AAV2 on HSV-1-induced DNA damage responses (DDR). We observed that the ATM kinase was activated in cells coinfected with AAV2 and HSV-1. We also found that phosphorylated ATR kinase and its cofactor ATR-interacting protein were recruited into AAV2 RCs, but ATR signaling was not activated. DNA-PKcs, another main kinase in the DDR, was degraded during HSV-1 infection in an ICP0-dependent manner, and this degradation was markedly delayed during AAV2 coinfection. Furthermore, we detected phosphorylation of DNA-PKcs during AAV2 but not HSV-1 replication. The AAV2-mediated delay in DNA-PKcs degradation affected signaling through downstream substrates. Overall, our results demonstrate that coinfection with HSV-1 and AAV2 provokes a cellular DDR which is distinct from that induced by HSV-1 alone.
Figures







Similar articles
-
Adeno-associated virus replication induces a DNA damage response coordinated by DNA-dependent protein kinase.J Virol. 2009 Jun;83(12):6269-78. doi: 10.1128/JVI.00318-09. Epub 2009 Apr 1. J Virol. 2009. PMID: 19339345 Free PMC article.
-
Enhanced phosphorylation of transcription factor sp1 in response to herpes simplex virus type 1 infection is dependent on the ataxia telangiectasia-mutated protein.J Virol. 2007 Sep;81(18):9653-64. doi: 10.1128/JVI.00568-07. Epub 2007 Jul 3. J Virol. 2007. PMID: 17609267 Free PMC article.
-
Impact of the MRN Complex on Adeno-Associated Virus Integration and Replication during Coinfection with Herpes Simplex Virus 1.J Virol. 2015 Jul;89(13):6824-34. doi: 10.1128/JVI.00171-15. Epub 2015 Apr 22. J Virol. 2015. PMID: 25903339 Free PMC article.
-
The Interplay between Adeno-Associated Virus and its Helper Viruses.Viruses. 2020 Jun 19;12(6):662. doi: 10.3390/v12060662. Viruses. 2020. PMID: 32575422 Free PMC article. Review.
-
Us3 Protein Kinase Encoded by HSV: The Precise Function and Mechanism on Viral Life Cycle.Adv Exp Med Biol. 2018;1045:45-62. doi: 10.1007/978-981-10-7230-7_3. Adv Exp Med Biol. 2018. PMID: 29896662 Review.
Cited by
-
Design stars: how small DNA viruses remodel the host nucleus.Future Virol. 2012 May 1;7(5):445-459. doi: 10.2217/FVL.12.38. Future Virol. 2012. PMID: 22754587 Free PMC article.
-
Viral and Cellular Components of AAV2 Replication Compartments.Open Virol J. 2013 Oct 31;7:98-120. doi: 10.2174/1874357901307010098. eCollection 2013. Open Virol J. 2013. PMID: 24222808 Free PMC article.
-
Recent Advances in Molecular Biology of Human Bocavirus 1 and Its Applications.Front Microbiol. 2021 Jun 16;12:696604. doi: 10.3389/fmicb.2021.696604. eCollection 2021. Front Microbiol. 2021. PMID: 34220786 Free PMC article. Review.
-
For better or worse: crosstalk of parvovirus and host DNA damage response.Front Immunol. 2024 Feb 23;15:1324531. doi: 10.3389/fimmu.2024.1324531. eCollection 2024. Front Immunol. 2024. PMID: 38464523 Free PMC article. Review.
-
Efficient herpes simplex virus 1 replication requires cellular ATR pathway proteins.J Virol. 2013 Jan;87(1):531-42. doi: 10.1128/JVI.02504-12. Epub 2012 Oct 24. J Virol. 2013. PMID: 23097436 Free PMC article.
References
-
- Ahn JY, Schwarz JK, Piwnica-Worms H, Canman CE. 2000. Threonine 68 phosphorylation by ataxia telangiectasia mutated is required for efficient activation of Chk2 in response to ionizing radiation. Cancer Res. 60:5934–5936 - PubMed
-
- Anantha RW, Vassin VM, Borowiec JA. 2007. Sequential and synergistic modification of human RPA stimulates chromosomal DNA repair. J. Biol. Chem. 282:35910–35923 - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Molecular Biology Databases
Research Materials
Miscellaneous