P53 and HTERT Determine Sensitivity to Viral Apoptosis

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2007 Sep 15

PMID 17855516

Citations 13

Authors

Marie L Nguyen

Rachel M Kraft

Martine Aubert

Edward Goodwin

Daniel DiMaio

John A Blaho

Affiliations

Soon will be listed here.

Abstract

Apoptosis is a potent host defense against microbes. Most viruses have adapted strategies to counteract this response. Herpes simplex virus (HSV) produces a balance between pro- and antiapoptotic processes during infection. When antiapoptotic signals become limiting, infected cells die through HSV-dependent apoptosis (HDAP). Oncogenic pathways were previously implicated in HDAP susceptibility. Here, we exploited our ability to selectively express all, one, or no oncogenes in the well-defined HeLa cell system to dissect the requirements for HDAP. Human papillomavirus E6 and E7 oncogene expression was inhibited by the E2 viral repressor. Sole expression of E6 mediated HDAP sensitization. Next, two known cellular targets of E6 were independently modulated. This demonstrated that E6 sensitizes HeLa cells to HDAP through hTERT and p53. Given the universality of the apoptotic antiviral response, p53 and telomerase regulation will likely be important for counteracting host defenses in many other viral infections.

Citing Articles

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References

Scheffner M, Werness B, Huibregtse J, Levine A, Howley P . The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell. 1990; 63(6):1129-36. DOI: 10.1016/0092-8674(90)90409-8. View

Huibregtse J, Scheffner M, Howley P . A cellular protein mediates association of p53 with the E6 oncoprotein of human papillomavirus types 16 or 18. EMBO J. 1991; 10(13):4129-35. PMC: 453163. DOI: 10.1002/j.1460-2075.1991.tb04990.x. View

Hwang E, Riese 2nd D, Settleman J, Nilson L, Honig J, Flynn S . Inhibition of cervical carcinoma cell line proliferation by the introduction of a bovine papillomavirus regulatory gene. J Virol. 1993; 67(7):3720-9. PMC: 237735. DOI: 10.1128/JVI.67.7.3720-3729.1993. View

Scheffner M, Huibregtse J, Vierstra R, Howley P . The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell. 1993; 75(3):495-505. DOI: 10.1016/0092-8674(93)90384-3. View

Sung Y, Choi Y, Cheong C, Lee H . The pleiotropy of telomerase against cell death. Mol Cells. 2005; 19(3):303-9. View

Clemens M . Epstein-Barr virus: inhibition of apoptosis as a mechanism of cell transformation. Int J Biochem Cell Biol. 2005; 38(2):164-9. DOI: 10.1016/j.biocel.2005.09.014. View

Taylor J, Barry M . Near death experiences: poxvirus regulation of apoptotic death. Virology. 2005; 344(1):139-50. DOI: 10.1016/j.virol.2005.09.032. View

Sabri F, Granath F, Hjalmarsson A, Aurelius E, Skoldenberg B . Modulation of sFas indicates apoptosis in human herpes simplex encephalitis. J Neuroimmunol. 2005; 171(1-2):171-6. DOI: 10.1016/j.jneuroim.2005.10.003. View

DeFilippis R, Goodwin E, Wu L, DiMaio D . Endogenous human papillomavirus E6 and E7 proteins differentially regulate proliferation, senescence, and apoptosis in HeLa cervical carcinoma cells. J Virol. 2002; 77(2):1551-63. PMC: 140828. DOI: 10.1128/jvi.77.2.1551-1563.2003. View

10.

Perkins D, Gyure K, Pereira E, Aurelian L . Herpes simplex virus type 1-induced encephalitis has an apoptotic component associated with activation of c-Jun N-terminal kinase. J Neurovirol. 2003; 9(1):101-11. DOI: 10.1080/13550280390173427. View

11.

Miles D, Athmanathan S, Thakur A, Willcox M . A novel apoptotic interaction between HSV-1 and human corneal epithelial cells. Curr Eye Res. 2003; 26(3-4):165-74. DOI: 10.1076/ceyr.26.3.165.14899. View

12.

Aubert M, Blaho J . Viral oncoapoptosis of human tumor cells. Gene Ther. 2003; 10(17):1437-45. DOI: 10.1038/sj.gt.3302004. View

13.

Koyama A, Adachi A, Irie H . Physiological significance of apoptosis during animal virus infection. Int Rev Immunol. 2003; 22(5-6):341-59. DOI: 10.1080/08830180305210. View

14.

Boutell C, Everett R . The herpes simplex virus type 1 (HSV-1) regulatory protein ICP0 interacts with and Ubiquitinates p53. J Biol Chem. 2003; 278(38):36596-602. DOI: 10.1074/jbc.M300776200. View

15.

Horner S, DeFilippis R, Manuelidis L, DiMaio D . Repression of the human papillomavirus E6 gene initiates p53-dependent, telomerase-independent senescence and apoptosis in HeLa cervical carcinoma cells. J Virol. 2004; 78(8):4063-73. PMC: 374296. DOI: 10.1128/jvi.78.8.4063-4073.2004. View

16.

Psyrri A, DeFilippis R, Edwards A, Yates K, Manuelidis L, DiMaio D . Role of the retinoblastoma pathway in senescence triggered by repression of the human papillomavirus E7 protein in cervical carcinoma cells. Cancer Res. 2004; 64(9):3079-86. DOI: 10.1158/0008-5472.can-03-3739. View

17.

Boutell C, Everett R . Herpes simplex virus type 1 infection induces the stabilization of p53 in a USP7- and ATM-independent manner. J Virol. 2004; 78(15):8068-77. PMC: 446092. DOI: 10.1128/JVI.78.15.8068-8077.2004. View

18.

Munger K, Baldwin A, Edwards K, Hayakawa H, Nguyen C, Owens M . Mechanisms of human papillomavirus-induced oncogenesis. J Virol. 2004; 78(21):11451-60. PMC: 523272. DOI: 10.1128/JVI.78.21.11451-11460.2004. View

19.

Miles D, Willcox M, Athmanathan S . Ocular and neuronal cell apoptosis during HSV-1 infection: a review. Curr Eye Res. 2004; 29(2-3):79-90. DOI: 10.1080/02713680490504669. View

20.

KERR J, Wyllie A, Currie A . Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972; 26(4):239-57. PMC: 2008650. DOI: 10.1038/bjc.1972.33. View