Virologica Sinica

, Volume 30, Issue 2, pp 122–129 | Cite as

Polyomavirus interaction with the DNA damage response

  • Joshua L. Justice
  • Brandy Verhalen
  • Mengxi Jiang
Review

Abstract

Viruses are obligate intracellular parasites that subvert cellular metabolism and pathways to mediate their own replication—normally at the expense of the host cell. Polyomaviruses are a group of small DNA viruses, which have long been studied as a model for eukaryotic DNA replication. Polyomaviruses manipulate host replication proteins, as well as proteins involved in DNA maintenance and repair, to serve as essential cofactors for productive infection. Moreover, evidence suggests that polyomavirus infection poses a unique genotoxic threat to the host cell. In response to any source of DNA damage, cells must initiate an effective DNA damage response (DDR) to maintain genomic integrity, wherein two protein kinases, ataxia telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR), are major regulators of DNA damage recognition and repair. Recent investigation suggests that these essential DDR proteins are required for productive polyomavirus infection. This review will focus on polyomaviruses and their interaction with ATM- and ATR-mediated DNA damage responses and the effect of this interaction on host genomic stability.

Keywords

polyomavirus DNA damage response genomic instability mitotic stress 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abend JR, Low JA, Imperiale MJ. 2010. Global effects of BKV infection on gene expression in human primary kidney epithelial cells. Virology, 397: 73–79.CrossRefPubMedCentralPubMedGoogle Scholar
  2. An P, Saenz Robles MT, Pipas JM. 2012. Large T antigens of polyomaviruses: Amazing molecular machines. Annu Rev Microbiol, 66: 213–236.CrossRefPubMedGoogle Scholar
  3. Andrabi S, Hwang JH, Choe JK, Roberts TM, Schaffhausen BS. 2011. Comparisons between murine polyomavirus and Simian virus 40 show significant differences in small t antigen function. J Virol, 85: 10649–10658.CrossRefPubMedCentralPubMedGoogle Scholar
  4. Banerjee P, DeJesus R, Gjoerup O, Schaffhausen BS. 2013. Viral interference with DNA repair by targeting of the single-stranded DNA binding protein rpa. PLoS Pathog, 9: e1003725.CrossRefPubMedCentralPubMedGoogle Scholar
  5. Boichuk S, Hu L, Hein J, Gjoerup OV. 2010. Multiple DNA damage signaling and repair pathways deregulated by Simian virus 40 large T antigen. J Virol, 84: 8007–8020.CrossRefPubMedCentralPubMedGoogle Scholar
  6. Bracken AP, Ciro M, Cocito A, Helin K. 2004. E2F target genes: Unraveling the biology. Trends Biochem Sci, 29: 409–417.CrossRefPubMedGoogle Scholar
  7. Cegielska A, Moarefi I, Fanning E, Virshup DM. 1994. T-antigen kinase inhibits simian virus 40 DNA replication by phospho-rylation of intact T antigen on serines 120 and 123. J Virol, 68: 269–275.PubMedCentralPubMedGoogle Scholar
  8. Chaurushiya MS, Weitzman MD. 2009. Viral manipulation of DNA repair and cell cycle checkpoints. DNA Repair (Amst), 8: 1166–1176.CrossRefGoogle Scholar
  9. Ciccia A, Elledge SJ. 2010. The DNA damage response: Making it safe to play with knives. Mol Cell, 40: 179–204.CrossRefPubMedCentralPubMedGoogle Scholar
  10. Dahl J, You J, Benjamin TL. 2005. Induction and utilization of an ATM signaling pathway by polyomavirus. J Virol, 79: 13007–13017.CrossRefPubMedCentralPubMedGoogle Scholar
  11. DeCaprio JA, Garcea RL. 2013. A cornucopia of human polyoma-viruses. Nat Rev Microbiol, 11: 264–276.CrossRefPubMedCentralPubMedGoogle Scholar
  12. Demetriou SK, Ona-Vu K, Sullivan EM, Dong TK, Hsu SW, Oh DH. 2012. Defective DNA repair and cell cycle arrest in cells expressing merkel cell polyomavirus T antigen. Int J Cancer, 131: 1818–1827.CrossRefPubMedCentralPubMedGoogle Scholar
  13. Dey D, Dahl J, Cho S, Benjamin TL. 2002. Induction and bypass of p53 during productive infection by polyomavirus. Journal of Virology, 76: 9526–9532.CrossRefPubMedCentralPubMedGoogle Scholar
  14. Dyson N, Bernards R, Friend SH, Gooding LR, Hassell JA, Major EO, Pipas JM, Vandyke T, Harlow E. 1990. Large T antigens of many polyomaviruses are able to form complexes with the retinoblastoma protein. J Virol, 64: 1353–1356.PubMedCentralPubMedGoogle Scholar
  15. Erickson KD, Bouchet-Marquis C, Heiser K, Szomolanyi-Tsuda E, Mishra R, Lamothe B, Hoenger A, Garcea RL. 2012. Virion assembly factories in the nucleus of polyomavirus-infected cells. PLoS Pathog, 8: e1002630.CrossRefPubMedCentralPubMedGoogle Scholar
  16. Feng H, Shuda M, Chang Y, Moore PS. 2008. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science, 319: 1096–1100.CrossRefPubMedCentralPubMedGoogle Scholar
  17. Garcea RL, Imperiale MJ. 2003. Simian virus 40 infection of humans. J Virol, 77: 5039–5045.CrossRefPubMedCentralPubMedGoogle Scholar
  18. Gjoerup O, Chang Y. 2010. Update on human polyomaviruses and cancer. Adv Cancer Res, 106: 1–51.CrossRefPubMedGoogle Scholar
  19. Hein J, Boichuk S, Wu J, Cheng Y, Freire R, Jat PS, Roberts TM, Gjoerup OV. 2009. Simian virus 40 large T antigen disrupts genome integrity and activates a DNA damage response via Bub1 binding. J Virol, 83: 117–127.CrossRefPubMedCentralPubMedGoogle Scholar
  20. Hoeijmakers JH. 2009. DNA damage, aging, and cancer. N Engl J Med, 361: 1475–1485.CrossRefPubMedGoogle Scholar
  21. Hu L, Filippakis H, Huang H, Yen TJ, Gjoerup OV. 2013. Replication stress and mitotic dysfunction in cells expressing simian virus 40 large T antigen. J Virol, 87: 13179–13192.CrossRefPubMedCentralPubMedGoogle Scholar
  22. Jiang M, Zhao L, Gamez M, Imperiale MJ. 2012. Roles of ATM and ATR-mediated DNA damage responses during lytic BK polyomavirus infection. PLoS Pathog, 8: e1002898.CrossRefPubMedCentralPubMedGoogle Scholar
  23. Kassem A, Schopflin A, Diaz C, Weyers W, Stickeler E, Werner M, Zur Hausen A. 2008. Frequent detection of merkel cell polyomavirus in human merkel cell carcinomas and identification of a unique deletion in the VP1 gene. Cancer Res, 68: 5009–5013.CrossRefPubMedGoogle Scholar
  24. Li J, Diaz J, Wang X, Tsang SH, You J. 2014. Phosphorylation of merkel cell polyomavirus large T antigen at serine 816 by atm kinase induces apoptosis in host cells. J Biol Chem, 290: 1874–1884.CrossRefPubMedGoogle Scholar
  25. Li J, Wang X, Diaz J, Tsang SH, Buck CB, You J. 2013. Merkel cell polyomavirus large T antigen disrupts host genomic integrity and inhibits cellular proliferation. J Virol, 87: 9173–9188.CrossRefPubMedCentralPubMedGoogle Scholar
  26. Lilley CE, Chaurushiya MS, Boutell C, Everett RD, Weitzman MD. 2011. The intrinsic antiviral defense to incoming HSV-1 genomes includes specific DNA repair proteins and is counteracted by the viral protein ICP0. PLoS Pathog, 7: e1002084.CrossRefPubMedCentralPubMedGoogle Scholar
  27. Liu Q, Guntuku S, Cui XS, Matsuoka S, Cortez D, Tamai K, Luo G, Carattini-Rivera S, DeMayo F, Bradley A, Donehower LA, Elledge SJ. 2000. Chk1 is an essential kinase that is regulated by atr and required for the G(2)/M DNA damage checkpoint. Genes Dev, 14: 1448–1459.CrossRefPubMedCentralPubMedGoogle Scholar
  28. Luftig MA. 2014. Viruses and the DNA damage response: Activation and antagonism. Annu Rev Virol, 1: 605–625.CrossRefGoogle Scholar
  29. Luo Y, Qiu J. 2013. Parvovirus infection-induced DNA damage response. Future Virol, 8: 245–257.CrossRefPubMedCentralPubMedGoogle Scholar
  30. Moens U, Van Ghelue M, Ehlers B. 2014. Are human polyomaviruses co-factors for cancers induced by other oncoviruses?. Rev Med Virol, 24: 343–360.CrossRefPubMedGoogle Scholar
  31. Mullane KP, Ratnofsky M, Cullere X, Schaffhausen B. 1998. Signaling from polyomavirus middle T and small T defines different roles for protein phosphatase 2A. Mol Cell Biol, 18: 7556–7564.PubMedCentralPubMedGoogle Scholar
  32. Novoa RR, Calderita G, Arranz R, Fontana J, Granzow H, Risco C. 2005. Virus factories: Associations of cell organelles for viral replication and morphogenesis. Biol Cell, 97: 147–172.CrossRefPubMedGoogle Scholar
  33. Okubo E, Lehman JM, Friedrich TD. 2003. Negative regulation of mitotic promoting factor by the checkpoint kinase Chk1 in simian virus 40 lytic infection. J Virol, 77: 1257–1267.CrossRefPubMedCentralPubMedGoogle Scholar
  34. Orba Y, Suzuki T, Makino Y, Kubota K, Tanaka S, Kimura T, Sawa H. 2010. Large T antigen promotes JC virus replication in G2- arrested cells by inducing ATM- and ATR-mediated G2 checkpoint signaling. J Biol Chem, 285: 1544–1554.CrossRefPubMedCentralPubMedGoogle Scholar
  35. Pietruska JR, Kane AB. 2007. SV40 oncoproteins enhance asbestos-induced DNA double-strand breaks and abrogate senescence in murine mesothelial cells. Cancer Res, 67: 3637–3645.CrossRefPubMedGoogle Scholar
  36. Pinto M, Dobson S. 2014. Bk and jc virus: A review. J Infect, 68Suppl 1: S2–8.CrossRefPubMedGoogle Scholar
  37. Pipas JM, Levine AJ. 2001. Role of t antigen interactions with p53 in tumorigenesis. Semin Cancer Biol, 11: 23–30.CrossRefPubMedGoogle Scholar
  38. Pores Fernando AT, Andrabi S, Cizmecioglu O, Zhu C, Livingston DM, Higgins JM, Schaffhausen BS, Roberts TM. 2014. Polyoma small T antigen triggers cell death via mitotic catastrophe. Oncogene. doi: 10.1038/onc.2014.192.Google Scholar
  39. Raghava S, Giorda KM, Romano FB, Heuck AP, Hebert DN. 2011. The SV40 late protein VP4 is a viroporin that forms pores to disrupt membranes for viral release. PLoS Pathog, 7: e1002116.CrossRefPubMedCentralPubMedGoogle Scholar
  40. Rohaly G, Korf K, Dehde S, Dornreiter I. 2010. Simian virus 40 activates ATR-Delta p53 signaling to override cell cycle and DNA replication control. J Virol, 84: 10727–10747.CrossRefPubMedCentralPubMedGoogle Scholar
  41. Shi Y, Dodson GE, Shaikh S, Rundell K, Tibbetts RS. 2005. Ataxia-telangiectasia-mutated (ATM) is a T-antigen kinase that controls SV40 viral replication in vivo. J Biol Chem, 280: 40195–40200.CrossRefPubMedGoogle Scholar
  42. Sowd GA, Li NY, Fanning E. 2013. Atm and atr activities maintain replication fork integrity during SV40 chromatin replication. PLoS Pathog, 9: e1003283.CrossRefPubMedCentralPubMedGoogle Scholar
  43. Sowd GA, Mody D, Eggold J, Cortez D, Friedman KL, Fanning E. 2014. SV40 utilizes ATM kinase activity to prevent non-homologous end joining of broken viral DNA replication products. PLoS Pathog, 10: e1004536.CrossRefPubMedCentralPubMedGoogle Scholar
  44. Stracker TH, Carson CT, Weitzman MD. 2002. Adenovirus oncoproteins inactivate the Mre11-Rad50-Nbs1 DNA repair complex. Nature, 418: 348–352.CrossRefPubMedGoogle Scholar
  45. Sweet BH, Hilleman MR. 1960. The vacuolating virus, S.V. 40. Proc Soc Exp Biol Med, 105: 420–427.CrossRefPubMedGoogle Scholar
  46. Trojanek J, Croul S, Ho T, Wang JY, Darbinyan A, Nowicki M, Del Valle L, Skorski T, Khalili K, Reiss K. 2006. T-antigen of the human polyomavirus jc attenuates faithful DNA repair by forcing nuclear interaction between IRS-1 and Rad51. J Cell Physiol, 206: 35–46.CrossRefPubMedGoogle Scholar
  47. Tsang SH, Wang X, Li J, Buck CB, You J. 2014. Host DNA damage response factors localize to merkel cell polyomavirus DNA replication sites to support efficient viral DNA replication. J Virol, 88: 3285–3297.CrossRefPubMedCentralPubMedGoogle Scholar
  48. Verhalen B, Justice JL, Imperiale MJ, Jiang M. 2015. Viral DNA replication-dependent DNA damage response activation during bk polyomavirus infection. J Virol, 89: 5032–5039.CrossRefPubMedGoogle Scholar
  49. Wileman T. 2007. Aggresomes and pericentriolar sites of virus assembly: Cellular defense or viral design? Annu Rev Microbiol, 61: 149–167.CrossRefPubMedGoogle Scholar
  50. Wu X, Avni D, Chiba T, Yan F, Zhao Q, Lin Y, Heng H, Livingston D. 2004. SV40 T antigen interacts with nbs1 to disrupt DNA replication control. Genes Dev, 18: 1305–1316.CrossRefPubMedCentralPubMedGoogle Scholar
  51. Yu G, Greninger AL, Isa P, Phan TG, Martinez MA, de la Luz Sanchez M, Contreras JF, Santos-Preciado JI, Parsonnet J, Miller S, DeRisi JL, Delwart E, Arias CF, Chiu CY. 2012. Discovery of a novel polyomavirus in acute diarrheal samples from children. PLoS One, 7: e49449.CrossRefPubMedCentralPubMedGoogle Scholar
  52. Zhao X, Madden-Fuentes RJ, Lou BX, Pipas JM, Gerhardt J, Rigell CJ, Fanning E. 2008. Ataxia telangiectasia-mutated damage-signaling kinase- and proteasome-dependent destruction of Mre11-Rad50-Nbs1 subunits in Simian virus 40-infected primate cells. J Virol, 82: 5316–5328.CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Wuhan Institute of Virology, CAS and Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Joshua L. Justice
    • 1
  • Brandy Verhalen
    • 1
  • Mengxi Jiang
    • 1
  1. 1.Department of MicrobiologyUniversity of Alabama at BirminghamBirminghamUSA

Personalised recommendations