Marek's Disease Virus Disables the ATR-Chk1 Pathway by Activating STAT3

Journal of Virology
Xue LianYingjuan Qian

Abstract

Oncogenic virus replication often leads to genomic instability, causing DNA damage and inducing the DNA damage response (DDR) pathway. The DDR pathway is a cellular pathway that senses DNA damage and regulates the cell cycle to maintain genomic stability. Therefore, the DDR pathway is critical for the viral lifecycle and tumorigenesis. Marek's disease virus (MDV), an alphaherpesvirus that causes lymphoma in chickens, has been shown to induce DNA damage in infected cells. However, the interaction between MDV and the host DDR is unclear. In this study, we observed that MDV infection causes DNA strand breakage in chicken fibroblast (CEF) cells along with an increase in the DNA damage markers p53 and p21. Interestingly, we showed that phosphorylation of STAT3 was increased during MDV infection, concomitantly with a decrease of Chk1 phosphorylation. In addition, we found that MDV infection was enhanced by VE-821, an ATR-specific inhibitor, but attenuated by hydroxyurea, an ATR activator. Moreover, inhibition of STAT3 phosphorylation by Stattic eliminates the ability of MDV to inhibit Chk1 phosphorylation. Finally, we showed that MDV replication was decreased by Stattic treatment. Taken together, these results suggest that MDV disabl...Continue Reading

References

Apr 15, 1997·Proceedings of the National Academy of Sciences of the United States of America·K TakedaS Akira
Oct 24, 2000·Journal of Virology·D J McGeochA C Ralph
Sep 26, 2001·The Journal of Biological Chemistry·S BurmaD J Chen
Nov 27, 2001·Science·D CortezS J Elledge
Sep 5, 2002·Nature Reviews. Molecular Cell Biology·David E Levy, J E Darnell
Jan 27, 2004·The Journal of Biological Chemistry·Irene M WardJunjie Chen
Jul 29, 2004·DNA Repair·Sandeep Burma, David J Chen
Mar 1, 2005·Oncogene·Daniel J DauerEric B Haura
Sep 29, 2005·Journal of Virology·Jean DahlThomas L Benjamin
Sep 30, 2005·Avian Pathology : Journal of the W.V.P.A·R L WitterK A Schat
Dec 23, 2006·Nature Reviews. Immunology·Hua YuDrew Pardoll
Jul 3, 2008·Nature Reviews. Molecular Cell Biology·Karlene A Cimprich, David Cortez
Jan 1, 1975·Avian Pathology : Journal of the W.V.P.A·V V Bulow, P M Biggs
Jan 15, 2009·The Journal of Pathology·Shikha BosePaul G Murray
Aug 4, 2009·Veterinary Immunology and Immunopathology·Hikmet KelesYilmaz Dundar
Oct 24, 2009·Nature Reviews. Cancer·Hua YuRichard Jove
Jun 23, 2010·Proceedings of the National Academy of Sciences of the United States of America·Andrew N BlackfordAndrew S Turnell
Jun 29, 2010·FEBS Letters·Frederick A Derheimer, Michael B Kastan
Aug 10, 2010·Annual Review of Microbiology·Matthew D WeitzmanMira S Chaurushiya
Sep 2, 2010·International Journal of Experimental Pathology·Seán P BarryAnastasis Stephanou
Sep 20, 2011·Future Virology·Pavel A Nikitin, Micah A Luftig
Jan 14, 2012·British Journal of Cancer·P A Nikitin, M A Luftig
Jul 4, 2012·Antioxidants & Redox Signaling·Qi MaEnrique A Mesri
Aug 3, 2012·The Journal of General Virology·Andrew S Turnell, Roger J Grand
Aug 23, 2012·PLoS Pathogens·April J SchumacherSandra K Weller
Oct 26, 2012·Journal of Virology·Kareem N MohniSandra K Weller
Mar 19, 2014·Proceedings of the National Academy of Sciences of the United States of America·Siva KogantiSumita Bhaduri-McIntosh
Jun 27, 2014·Journal of Virology·Richard O Adeyemi, David J Pintel
May 27, 2015·Viruses·Robert Hollingworth, Roger J Grand
Jun 10, 2015·Viruses·Robert HollingworthRoger J Grand
Jul 28, 2016·Frontiers in Microbiology·Xiaofan Li, Sumita Bhaduri-McIntosh
Nov 30, 2016·Veterinary Research·Nitish BoodhooShahriar Behboudi

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