Skip to main content
SpringerLink
Log in

Caspase-3-dependent reactivation of latent herpes simplex virus type 1 in sensory neuronal cultures

  • Short Communication
  • Published:
Journal of NeuroVirology Aims and scope Submit manuscript

Abstract

Life-long latent herpes simplex virus type 1 (HSV-1) is harbored in sensory neurons where sporadic reactivation occurs. Reactivation stimuli may involve activation of apoptotic signaling in the neuron. Previous experiments have demonstrated that reactivation of latent HSV-1 in dorsal root ganglion (DRG) neuronal cultures occurred following nerve growth factor (NGF) deprivation. NGF deprivation stimulates apoptotic signaling by activating the proapoptotic proteolytic enzyme, caspase-3. When DRG neuronal cultures harboring latent HSV-1 were treated with a caspase-3-specific inhibitor, NGF deprivation—induced reactivation was significantly reduced. Interestingly, the caspase-3 inhibitor had no effect on productive HSV-1 infection. Furthermore, activation of caspase-3 with either C2-ceramide or a recombinant adenovirus expressing caspase-3 caused significant HSV-1 reactivation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  • Ahmed M, Lock M, Miller CG, Fraser NW (2002). Regions of the herpes simplex virus type 1 latency-associated transcript that protects cells from apoptosis in vitro and protect neuronal cells in vivo. J Virol 76: 717–729.

    Article  PubMed  CAS  Google Scholar 

  • Aubert M, Blaho JA (1999). The herpes simplex virus type 1 regulatory protein ICP2 7 is required for the prevention of apoptosis in infected human cells. J Virol 73: 2803–2813.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Bader C, Crumpacker CS, Schnipper LE, Ransil B, Clark JE (1978). The natural history of recurrent facial-oral infection with herpes simplex virus. J Infect Dis 138: 897–905.

    PubMed  CAS  Google Scholar 

  • Baringer JR, Swoveland P (1973). Recovery of herpes simplex virus from human trigeminal ganglions. N Engl J Med 288: 648–650.

    Article  PubMed  CAS  Google Scholar 

  • Barrett G, Bartlett P (1994). The p75 nerve growth factor receptor mediates survival or death depending on the stages of sensory development. Proc Natl Acad Sci U S A 91: 6501–6505.

    Article  PubMed  CAS  Google Scholar 

  • Boldin MP, Goncharov TM, Goltsev YV, Wallach D (1996). Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/Apo-1- and TNF receptor-induced cell death. Cell 85: 803–815.

    Article  PubMed  CAS  Google Scholar 

  • Brann AB, Tcherpakov M, Williams IM, Futerman AH, Fainzilber M (2002). Nerve growth factor-induced p75 mediated death of cultures hippocampal neurons is age-dependent and transduced through ceramide generated by neutral sphingomylinase. J Biol Chem 277: 9812–9818.

    Article  PubMed  CAS  Google Scholar 

  • Colgin MA, Smith RL, Wilcox CL (2001). Inducible cyclic AMP early repressor produces reactivation of latent herpes simplex virus type 1 in neurons in vitro. J Virol 75: 2912–2920.

    Article  PubMed  CAS  Google Scholar 

  • Cook SD (1992). Herpes simplex virus in the eye. Br J Ophthalmol 76: 365–366.

    Article  PubMed  CAS  Google Scholar 

  • Doerig C, Pizer LI, Wilcox CL (1991). Detection of latency-associated transcripts in neuronal cultures during the latent infection with herpes simplex virus type 1. J Virol 183: 423–426.

    Article  CAS  Google Scholar 

  • Galvan V, Brandimarti R, Munger J, Roizman B (2000). Bcl-2 blocks caspase-dependent pathway of apoptosis activated by herpes simplex virus 1 infection in Hep-2 cells. J Virol 74: 1931–1938.

    Article  PubMed  CAS  Google Scholar 

  • Galvan V, Roizman B (1998). Herpes simplex virus 1 induces and blocks apoptosis at multiple steps during infection and protects cells from exogenous inducers in a cell-type-dependent manner. Proc Natl Acad Sci U S A 95: 3931–3936.

    Article  PubMed  CAS  Google Scholar 

  • Gill JS, Windebank AJ (2000). Ceramide initiates NFκB-mediated caspase activation in neuronal apoptosis. Neurobiol Dis 7: 448–461.

    Article  PubMed  CAS  Google Scholar 

  • Hamburger V, Levi-Montalcini R (1949). Proliferation, differentiation and degeneration in the spinal ganglia of the chick embryo under normal and experimental conditions. J Exp Zool 111: 457–502.

    Article  PubMed  CAS  Google Scholar 

  • Inman M, Perng GC, Henderson G, Ghiasi H, Nesburn AB, Wechsler SL, Jones C (2001). Region of herpes simplex virus type 1 latency-associated transcript sufficient for wild-type spontaneous reactivation promotes cell survival in tissue culture. J Virol 75: 3636–3646.

    Article  PubMed  CAS  Google Scholar 

  • Itoh N, Yonehara S, Ishii A, Yonehara M, Mizushima S, Sameshima M, Hase A, Seto Y, Negata S (1991). The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell 55: 233–243.

    Article  Google Scholar 

  • Jerome KR, Fox R, Chen Z, Sears AE, Lee HY, Corey L (1999). Herpes simplex virus inhibits apoptosis through the action of two genes Us5 and Us3. J Virol 73: 8950–8957.

    PubMed  CAS  Google Scholar 

  • Kaplan DR, Hempstead BL, Martin-Zanca D, Chao MV, Parada LF (1991). The trk proto-oncogene product: a signal transducing receptor for nerve growth factor. Science 252: 554–554.

    Article  PubMed  CAS  Google Scholar 

  • Kaplan DR, Miller FD (2000). Neurotrophin signal transduction in the nervous system. Curr Opin Neurobiol 10: 381–391.

    Article  PubMed  CAS  Google Scholar 

  • Kuida K, Zheng TS, Na S, Kuan C, Yang D, Karasuyama H, Rakic P, Flavell RA (1996). Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice. Nature 384: 368–372.

    Article  PubMed  CAS  Google Scholar 

  • Kumar S, Colussi PA (1999). Prodomains-adaptors-oligomerization: the persuit of caspase activation in apoptosis. Trends Biol Sci 24: 1–4.

    Article  CAS  Google Scholar 

  • Martin-Zanca DS, Hughes SH, Barbacid M (1986). A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequence. Nature 319: 743–748.

    Article  PubMed  CAS  Google Scholar 

  • Munger J, Chee AV, Roizman B (2001). The US3 protein kinase blocks apoptosis induced by the dl120 mutant of herpes simplex virus type 1 at a pre-mitochondrial stage. J Virol 75: 5491–5497.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Rabizadeh S, Oh J, Zhong LT, Yang J, Bifler CM, Butcher LL, Bredesen DE (1993). Induction of apoptosis by low-affinity NGF receptor. Science 261: 345–348.

    Article  PubMed  CAS  Google Scholar 

  • Smith C, Farrah T, Goodwin R (1994a). The TNF receptor superfamily of cellular and viral proteins: activation, costimulation, and death. Cell 76: 959–962.

    Article  PubMed  CAS  Google Scholar 

  • Smith RL, Escudero JM, Wilcox CL (1994b). Regulation of the herpes simplex virus latency-associated transcripts during establishment of latency in sensory neurons in vitro. Virology 202: 49–60.

    Article  PubMed  CAS  Google Scholar 

  • Smith RL, Pizer LI, Johnson EM Jr, Wilcox CL (1992). Activation of second-messenger pathways reactivates latent herpes simplex virus in neuronal cultures. Virology 188: 311–318.

    Article  PubMed  CAS  Google Scholar 

  • Smith RL, Traul DL, Schaack J, Clayton GH, Staley KJ, Wilcox CL (2000). Characterization of promoter function and cell-type-specific expression from viral vectors in the nervous system. J Virol 74: 11254–11261.

    Article  PubMed  CAS  Google Scholar 

  • Smith RL, Wilcox CL (1996). In: Protocols for gene transfer in neuroscience: towards gene therapy of neurological disorders. Lowenstein PR, Enquist LW (eds). West Sussex: John Wiley & Sons, pp 221–231.

    Google Scholar 

  • Stevens JG (1989). Human herpes virus: a consideration of the latent state. Microbiol Rev 53: 318–332.

    PubMed  CAS  Google Scholar 

  • Volgelbaum MA, Tong JX, Rich KM (1998). Developmental regulation of apoptosis in dorsal root ganglion neurons. J Neurosci 18: 8928–8935.

    Google Scholar 

  • Wagner EK, Bloom DC (1997). Experimental investigation of herpes simplex virus latency. Clin Microbiol Rev 10: 419–443.

    PubMed  CAS  Google Scholar 

  • Wilcox CL, Johnson EM Jr (1987). Nerve growth factor deprivation results in the reactivation of latent herpes simplex virus in latency neurons in vitro. J Virol 61: 2311–2315.

    PubMed  CAS  Google Scholar 

  • Wilcox CL, Johnson EM Jr (1988). Characterization of nerve growth factor-dependent herpes simplex virus latency in neurons in vitro. J Virol 62: 393–399.

    PubMed  CAS  Google Scholar 

  • Wilcox CL, Smith RL, Freed CR, Johnson EM Jr (1990). Nerve growth factor-dependence of herpes simplex virus latency in peripheral sympathetic and sensory neurons in vitro. J Neurosci 10: 1268–1275.

    PubMed  CAS  Google Scholar 

  • Zhou G, Roizman B (2000). Wild-type herpes simplex virus 1 blocks programmed cell death and release of cytochrome c but not the translocation of mitochondrial apoptosis-inducing factor to the nuclei of human embryonic lung fibroblasts. J Virol 74: 9048–9053.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Microbiology, Colorado State University, Fort Collins, Colorado, USA

    Elizabeth A. Hunsperger & Christine L. Wilcox

  2. Centers for Disease Control and Prevention (CDC), Foothills Campus, PO Box 2087, 80522, Ft. Collins, CO, USA

    Elizabeth A. Hunsperger

Authors
  1. Elizabeth A. Hunsperger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christine L. Wilcox
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elizabeth A. Hunsperger.

Additional information

This research was supported by the National Research Service Award predoctoral fellowship awarded to EAH (F3111059) and the Public Health Service grant NS29042 awarded to CLW.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hunsperger, E.A., Wilcox, C.L. Caspase-3-dependent reactivation of latent herpes simplex virus type 1 in sensory neuronal cultures. Journal of NeuroVirology 9, 390–398 (2003). https://doi.org/10.1080/13550280390201678

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1080/13550280390201678

Keywords

Search

Navigation