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Apoptosis induction after herpes simplex virus infection differs according to cell type in vivo

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Abstract

We compared apoptosis induction in mice following three routes of infection. After intravenous infection, wild-type herpes simplex virus (HSV) types 1 and 2 and US3Δ mutants infected the adrenal gland and caused apoptosis. Corneal infection with wild-type virus resulted in apoptosis in a fraction of infected epithelium cells. Interestingly, many uninfected cells were apoptotic in the retina. Although neurons in the trigeminal ganglion were heavily infected, no apoptotic neurons were observed. Intracranial infection with wild-type virus resulted in HSV-infected cells inside the brain; however, most of the infected neurons escaped apoptosis. In contrast, infection with US3Δ and γ134.5Δ mutants caused apoptosis in infected neurons. Cleaved caspase-8 and p53 were detected in apoptotic cells in the adrenal gland and the brain; however, phospho-JNK was detected only in apoptotic cells of the brain. These results suggest that the activation of apoptotic signaling proteins differs depending on the host cell type and modulates the induction of apoptosis in HSV-infected cells.

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References

  1. Aita K, Irie H, Koyama AH, Fukuda A, Yoshida T, Shiga J (2001) Acute adrenal infection by HSV-1: role of apoptosis in viral replication. Arch Virol 146:2009–2020

    Article  CAS  PubMed  Google Scholar 

  2. Asano S, Honda T, Goshima F, Watanabe D, Miyake Y, Sugiura Y, Nishiyama Y (1999) US3 protein kinase of herpes simplex virus type 2 plays a role in protecting corneal epithelial cells from apoptosis in infected mice. J Gen Virol 80(Pt 1):51–56

    CAS  PubMed  Google Scholar 

  3. Asano S, Honda T, Goshima F, Nishiyama Y, Sugiura Y (2000) US3 protein kinase of herpes simplex virus protects primary afferent neurons from virus-induced apoptosis in ICR mice. Neurosci Lett 294:105–108

    Article  CAS  PubMed  Google Scholar 

  4. Aubert M, O’Toole J, Blaho JA (1999) Induction and prevention of apoptosis in human HEp-2 cells by herpes simplex virus type 1. J Virol 73:10359–10370

    CAS  PubMed  Google Scholar 

  5. Aurelian L (2005) HSV-induced apoptosis in herpes encephalitis. Curr Top Microbiol Immunol 289:79–111

    Article  CAS  PubMed  Google Scholar 

  6. Benetti L, Munger J, Roizman B (2003) The herpes simplex virus 1 US3 protein kinase blocks caspase-dependent double cleavage and activation of the proapoptotic protein BAD. J Virol 77:6567–6573

    Article  CAS  PubMed  Google Scholar 

  7. Benetti L, Roizman B (2004) Herpes simplex virus protein kinase US3 activates and functionally overlaps protein kinase A to block apoptosis. Proc Natl Acad Sci USA 101:9411–9416

    Article  CAS  PubMed  Google Scholar 

  8. Bigger JE, Tanigawa M, Zhang M, Atherton SS (2000) Murine cytomegalovirus infection causes apoptosis of uninfected retinal cells. Invest Ophthalmol Vis Sci 41:2248–2254

    CAS  PubMed  Google Scholar 

  9. Branco FJ, Fraser NW (2005) Herpes simplex virus type 1 latency-associated transcript expression protects trigeminal ganglion neurons from apoptosis. J Virol 79:9019–9025

    Article  CAS  PubMed  Google Scholar 

  10. Chou J, Kern ER, Whitley RJ, Roizman B (1990) Mapping of herpes simplex virus-1 neurovirulence to gamma 134.5, a gene nonessential for growth in culture. Science 250:1262–1266

    Article  CAS  PubMed  Google Scholar 

  11. Clem RJ, Fechheimer M, Miller LK (1991) Prevention of apoptosis by a baculovirus gene during infection of insect cells. Science 254:1388–1390

    Article  CAS  PubMed  Google Scholar 

  12. DeBiasi RL, Kleinschmidt-DeMasters BK, Richardson-Burns S, Tyler KL (2002) Central nervous system apoptosis in human herpes simplex virus and cytomegalovirus encephalitis. J Infect Dis 186:1547–1557

    Article  PubMed  Google Scholar 

  13. Diao L, Zhang B, Xuan C, Sun S, Yang K, Tang Y, Qiao W, Chen Q, Geng Y, Wang C (2005) Activation of c-Jun N-terminal kinase (JNK) pathway by HSV-1 immediate early protein ICP0. Exp Cell Res 308:196–210

    Article  CAS  PubMed  Google Scholar 

  14. Frame MC, Purves FC, McGeoch DJ, Marsden HS, Leader DP (1987) Identification of the herpes simplex virus protein kinase as the product of viral gene US3. J Gen Virol 68(Pt 10):2699–2704

    Article  CAS  PubMed  Google Scholar 

  15. Green DR, Knight RA, Melino G, Finazzi-Agro A, Orrenius S (2004) Ten years of publication in cell death. Cell Death Differ 11:2–3

    Article  CAS  PubMed  Google Scholar 

  16. Hargett D, McLean T, Bachenheimer SL (2005) Herpes simplex virus ICP27 activation of stress kinases JNK and p38. J Virol 79:8348–8360

    Article  CAS  PubMed  Google Scholar 

  17. Hata S, Koyama AH, Shiota H, Adachi A, Goshima F, Nishiyama Y (1999) Antiapoptotic activity of herpes simplex virus type 2: the role of US3 protein kinase gene. Microbes Infect 1:601–607

    Article  CAS  PubMed  Google Scholar 

  18. He B, Gross M, Roizman B (1998) The gamma134.5 protein of herpes simplex virus 1 has the structural and functional attributes of a protein phosphatase 1 regulatory subunit and is present in a high molecular weight complex with the enzyme in infected cells. J Biol Chem 273:20737–20743

    Article  CAS  PubMed  Google Scholar 

  19. Irie H, Kiyoshi A, Koyama AH (2004) A role for apoptosis induced by acute herpes simplex virus infection in mice. Int Rev Immunol 23:173–185

    Article  CAS  PubMed  Google Scholar 

  20. Koyama AH, Adachi A (1997) Induction of apoptosis by herpes simplex virus type 1. J Gen Virol 78(Pt 11):2909–2912

    CAS  PubMed  Google Scholar 

  21. Koyama AH, Akari H, Adachi A, Goshima F, Nishiyama Y (1998) Induction of apoptosis in HEp-2 cells by infection with herpes simplex virus type 2. Arch Virol 143:2435–2441

    Article  CAS  PubMed  Google Scholar 

  22. Koyama AH, Irie H, Fukumori T, Hata S, Iida S, Akari H, Adachi A (1998) Role of virus-induced apoptosis in a host defense mechanism against virus infection. J Med Invest 45:37–45

    CAS  PubMed  Google Scholar 

  23. Leopardi R, Roizman B (1996) The herpes simplex virus major regulatory protein ICP4 blocks apoptosis induced by the virus or by hyperthermia. Proc Natl Acad Sci USA 93:9583–9587

    Article  CAS  PubMed  Google Scholar 

  24. Liu J, Lin A (2005) Role of JNK activation in apoptosis: a double-edged sword. Cell Res 15:36–42

    Article  PubMed  Google Scholar 

  25. Mori I, Goshima F, Koshizuka T, Koide N, Sugiyama T, Yoshida T, Yokochi T, Kimura Y, Nishiyama Y (2003) The US3 protein kinase of herpes simplex virus attenuates the activation of the c-Jun N-terminal protein kinase signal transduction pathway in infected piriform cortex neurons of C57BL/6 mice. Neurosci Lett 351:201–205

    Article  CAS  PubMed  Google Scholar 

  26. Mori I, Goshima F, Watanabe D, Ito H, Koide N, Yoshida T, Liu B, Kimura Y, Yokochi T, Nishiyama Y (2006) Herpes simplex virus US3 protein kinase regulates virus-induced apoptosis in olfactory and vomeronasal chemosensory neurons in vivo. Microbes Infect 8:1806–1812

    Article  CAS  PubMed  Google Scholar 

  27. Murata T, Goshima F, Daikoku T, Takakuwa H, Nishiyama Y (2000) Expression of herpes simplex virus type 2 US3 affects the Cdc42/Rac pathway and attenuates c-Jun N-terminal kinase activation. Genes Cells 5:1017–1027

    Article  CAS  PubMed  Google Scholar 

  28. Murata T, Goshima F, Yamauchi Y, Koshizuka T, Takakuwa H, Nishiyama Y (2002) Herpes simplex virus type 2 US3 blocks apoptosis induced by sorbitol treatment. Microbes Infect 4:707–712

    Article  CAS  PubMed  Google Scholar 

  29. Nguyen ML, Kraft RM, Blaho JA (2005) African green monkey kidney Vero cells require de novo protein synthesis for efficient herpes simplex virus 1-dependent apoptosis. Virology 336:274–290

    Article  CAS  PubMed  Google Scholar 

  30. Nguyen ML, Blaho JA (2007) Apoptosis during herpes simplex virus infection. Adv Virus Res 69:67–97

    Article  CAS  PubMed  Google Scholar 

  31. Nishiyama Y, Yamada Y, Kurachi R, Daikoku T (1992) Construction of a US3 lacZ insertion mutant of herpes simplex virus type 2 and characterization of its phenotype in vitro and in vivo. Virology 190:256–268

    Article  CAS  PubMed  Google Scholar 

  32. Nishiyama Y, Murata T (2002) Anti-apoptotic protein kinase of herpes simplex virus. Trends Microbiol 10:105–107

    Article  CAS  PubMed  Google Scholar 

  33. Ogg PD, McDonell PJ, Ryckman BJ, Knudson CM, Roller RJ (2004) The HSV-1 Us3 protein kinase is sufficient to block apoptosis induced by overexpression of a variety of Bcl-2 family members. Virology 319:212–224

    Article  CAS  PubMed  Google Scholar 

  34. Ozaki N, Sugiura Y, Yamamoto M, Yokoya S, Wanaka A, Nishiyama Y (1997) Apoptosis induced in the spinal cord and dorsal root ganglion by infection of herpes simplex virus type 2 in the mouse. Neurosci Lett 228:99–102

    Article  CAS  PubMed  Google Scholar 

  35. Perkins D, Gyure KA, Pereira EF, Aurelian L (2003) Herpes simplex virus type 1-induced encephalitis has an apoptotic component associated with activation of c-Jun N-terminal kinase. J Neurovirol 9:101–111

    CAS  PubMed  Google Scholar 

  36. Perng GC, Jones C, Ciacci-Zanella J, Stone M, Henderson G, Yukht A, Slanina SM, Hofman FM, Ghiasi H, Nesburn AB, Wechsler SL (2000) Virus-induced neuronal apoptosis blocked by the herpes simplex virus latency-associated transcript. Science 287:1500–1503

    Article  CAS  PubMed  Google Scholar 

  37. Prindull G (1995) Apoptosis in the embryo and tumorigenesis. Eur J Cancer 31A:116–123

    Article  CAS  PubMed  Google Scholar 

  38. Sanfilippo CM, Blaho JA (2006) ICP0 gene expression is a herpes simplex virus type 1 apoptotic trigger. J Virol 80:6810–6821

    Article  CAS  PubMed  Google Scholar 

  39. Soliman TM, Sandri-Goldin RM, Silverstein SJ (1997) Shuttling of the herpes simplex virus type 1 regulatory protein ICP27 between the nucleus and cytoplasm mediates the expression of late proteins. J Virol 71:9188–9197

    CAS  PubMed  Google Scholar 

  40. Thompson CB (1995) Apoptosis in the pathogenesis and treatment of disease. Science 267:1456–1462

    Article  CAS  PubMed  Google Scholar 

  41. Watanabe D, Honda T, Nishio K, Tomita Y, Sugiura Y, Nishiyama Y (2000) Corneal infection of herpes simplex virus type 2–induced neuronal apoptosis in the brain stem of mice with expression of tumor suppressor gene (p53) and transcription factors. Acta Neuropathol 100:647–653

    Article  CAS  PubMed  Google Scholar 

  42. Wilson SE, He YG, Weng J, Li Q, McDowall AW, Vital M, Chwang EL (1996) Epithelial injury induces keratocyte apoptosis: hypothesized role for the interleukin-1 system in the modulation of corneal tissue organization and wound healing. Exp Eye Res 62:325–327

    Article  CAS  PubMed  Google Scholar 

  43. Yamamoto M, Kurachi R, Morishima T, Kito J, Nishiyama Y (1996) Immunohistochemical studies on the transneuronal spread of virulent herpes simplex virus type 2 and its US3 protein kinase-deficient mutant after ocular inoculation. Microbiol Immunol 40:289–294

    CAS  PubMed  Google Scholar 

  44. Zhang M, Atherton SS (2002) Apoptosis in the retina during MCMV retinitis in immunosuppressed BALB/c mice. J Clin Virol 25(Suppl 2):S137–S147

    Article  PubMed  Google Scholar 

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Acknowledgments

We thank Ms. Noma for technical support. This work was supported by a Grant-in-Aid for Scientific Research of Priority Areas from the Ministry of Education, Culture, Sports, Sciences, and Technology of Japan.

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Authors and Affiliations

  1. Department of Virology, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8560, Japan

    Shinichi Esaki, Fumi Goshima & Yukihiro Nishiyama

  2. Department of Otolaryngology, Head and Neck Surgery, Nagoya City University Graduate School of Medical Sciences and Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8602, Japan

    Shinichi Esaki, Sachiyo Katsumi & Shingo Murakami

  3. Department of Dermatology, Aichi Medical University, Nagakute, Aichi, 480-1195, Japan

    Daisuke Watanabe

  4. Department of Anatomy and Neuroscience, Kanazawa University Graduate School of Medicine, 13-1, Takara-machi, Kanazawa, 920-8040, Japan

    Noriyuki Ozaki

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  1. Shinichi Esaki
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  2. Fumi Goshima
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Correspondence to Fumi Goshima.

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Esaki, S., Goshima, F., Katsumi, S. et al. Apoptosis induction after herpes simplex virus infection differs according to cell type in vivo. Arch Virol 155, 1235–1245 (2010). https://doi.org/10.1007/s00705-010-0712-2

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  • DOI: https://doi.org/10.1007/s00705-010-0712-2

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