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Stress and reactivation of latent herpes simplex virus: A fusion of behavioral medicine and molecular biology

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Annals of Behavioral Medicine

Abstract

Since 1978, the study of health and behavior has become a major focus of scientists in psychology, psychiatry, nursing, neu-roscience, and in traditional medical science disciplines. Investigation of psychological or behavioral influences on biological systems has established that biobehavioral processes such as stress play an important role in disease processes. An excellent example of the interactions between stress and health outcomes is the reactivation of latent herpes simplex virus (HSV) leading to recurrent lesions. This article describes what is currently known about HSV latency and reactivation and considers some mechanisms by which stress-induced changes in the host’s immune and nervous systems might allow for either the establishment or reactivation of latent viral infections.

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References

  1. Krantz DS, Grunberg NE, Baum A: Health psychology.Annual Review of Psychology. 1985,36:349–383.

    Article  PubMed  CAS  Google Scholar 

  2. Ader R, Cohen N: The influence of conditioning on immune responses. In Ader R, Felten DL, Cohen N (eds),Psychoneuroim-munology. New York: Academic, 1991, 611–646.

    Google Scholar 

  3. Kiecolt-Glaser JK, Glaser R: Psychological influences on immunity.Psychosomatics. 1986, 27:621–624.

    PubMed  CAS  Google Scholar 

  4. Kiecolt-Glaser JK, Dura JR, Speicher CE, Trask OJ, Glaser R: Spousal caregivers of dementia victims: Longitudinal changes in immunity and health.Psychosomatic Medicine. 1991,55:345–362.

    Google Scholar 

  5. Glaser R, Kiecolt-Glaser JK, Bonneau RH, et al: Stress-induced modulation of the immune response to recombinant hepatitis B vaccine.Psychosomatic Medicine. 1992,54:22–29.

    PubMed  CAS  Google Scholar 

  6. Jabaaij L, Grosheide PM, Heijtink RA, et al: Influence of perceived psychological stress and distress on antibody response to low dose rDNA hepatitis B vaccine.Journal of Psychosomatic Research. 1993, 37:361–369.

    Article  PubMed  CAS  Google Scholar 

  7. Cohen S, Tyrrell DAJ, Smith AP: Psychological stress and susceptibility to the common cold.New England Journal of Medicine. 1991,525:606–612.

    Google Scholar 

  8. Glaser R, Kiecolt-Glaser JK, Speicher CE, Holliday JE: Stress, loneliness, and changes in herpesvirus latency.Journal of Behavioral Medicine. 1985,8:249–260.

    Article  PubMed  CAS  Google Scholar 

  9. Kiecolt-Glaser JK, Fisher LD, Ogrocki P, et al: Marital quality, marital disruption, and immune function.Psychosomatic Medicine. 1987,49:13–34.

    PubMed  CAS  Google Scholar 

  10. McKinnon W, Weisse CS, Reynolds CP, Bowles CA, Baum A: Chronic stress, leukocyte subpopulations, and humoral response to latent viruses.Health Psychology. 1989,8:389–402.

    Article  PubMed  CAS  Google Scholar 

  11. Whitley RJ, Gnann JWJ: The epidemiology and clinical manifestations of herpes simplex virus infections. In Roizman B, Whitley RJ, Lopez C (eds),The Human Herpesviruses. New York: Raven Press, 1993, 69–106.

    Google Scholar 

  12. Cook ML, Stevens JG: Pathogenesis of herpetic neuritis and ganglionitis in mice: Evidence of intra-axonal transport of infection.Infection and Immunity. 1973,7:272–288.

    PubMed  CAS  Google Scholar 

  13. Hill TJ: Herpes simplex virus latency. In Roizman B (ed),The Herpesviruses. New York: Plenum Press, 1985, 175.

    Google Scholar 

  14. Segal AL, Katcher AH, Bringtman VJ, Miller MF: Recurrent herpes labialis, recurrent apthous ulcers, and the menstrual cycles.Journal of Dental Research. 1974,53:797.

    PubMed  CAS  Google Scholar 

  15. Spruance SL: Pathogenesis of herpes simplex labialis: Experimental induction of lesions with UV light.Journal of Clinical Microbiology. 1985,22:366–368.

    PubMed  CAS  Google Scholar 

  16. Carlton CA, Kilbourne ED: Activation of latent herpes simplex virus by trigeminal sensory-root section.New England Journal of Medicine. 1952,246:172.

    Google Scholar 

  17. Pazin GJ, Ho M, Jannetta PJ: Herpes simplex reactivation after trigeminal nerve root decompression.Journal of Infectious Diseases. 1978,138:405.

    PubMed  CAS  Google Scholar 

  18. Nahmias AJ, Roizman B: Infection with herpes simplex viruses 1 and 2: II.New England Journal of Medicine. 1973,289.719–725.

    PubMed  CAS  Google Scholar 

  19. Jemmott J, Locke S: Psychosocial factors, immunologic mediation, and human susceptibility to infectious diseases.Psychological Bulletin. 1984,95:78–108.

    Article  PubMed  Google Scholar 

  20. Katcher AH, Brightman V, Luborsky L, Ship I: Prediction of the incidence of recurrent herpes labialis and systemic illness from psychological measurements.Journal of Dental Research. 1973,52:49–58.

    PubMed  CAS  Google Scholar 

  21. Luborsky L, Mintz J, Brightman V, Katcher AH: Herpes simplex virus and moods: A longitudinal study.Journal of Psychosomatic Research. 1976,2:543–548.

    Article  Google Scholar 

  22. Greenfield NS, Roessler R, Crosley AP: Ego strength and length of recovery from infectious mononucleosis.Journal of Nervous and Mental Disease. 1959,725:125–128.

    Google Scholar 

  23. Kasl SV, Evans AS, Neiderman JC: Psychosocial risk factors in the development of infectious mononucleosis.Psychosomatic Medicine. 1979,47:445–466.

    Google Scholar 

  24. KieflT E, Liebowitz D: Epstein-Barr virus and its replication. In Fields BN, Knipe DM, Chanock RM, et al (eds),Virology. New York. Raven Press, 1990, 1889–1920.

    Google Scholar 

  25. Roizman B, Sears AE: Herpes simplex viruses and their replication. In Roizman B, Whitley RJ, Lopez C (eds),The Human Herpesviruses. New York: Raven Press, 1993, 11–68.

    Google Scholar 

  26. Jenkins FJ, Martin J: Role of the herpes simplex virus 1 internal repeat sequences in pathogenicity.Intervirology. 1990,57:128–138.

    Google Scholar 

  27. Wilcox C, Johnson EJ: Characterization of nerve growth factor-dependent herpes simplex virus latency in neuronsin vitro.Journal of Virology. 1988,62:393–399.

    PubMed  CAS  Google Scholar 

  28. Wilcox CL, Smith RL, Freed CR, Johnson Jr. EM: Nerve growth factor-dependence of herpes simplex virus latency in peripheral sympathetic and sensory neuronsin vitro.Journal ofNeuroscience. 1990,70:1268–1275.

    Google Scholar 

  29. Greene LA, Shooter EM: The nerve growth factor: Biochemistry, synthesis, and mechanism of action.Annual Review of Neurosci-ence. 1980,5:353–102.

    Article  Google Scholar 

  30. Thoenen H, Barde Y-A: Physiology of nerve growth factor.Physiology Reviews. 1980,60:1284–1335.

    CAS  Google Scholar 

  31. Korsching S, Thoenen H: Nerve growth factor in sympathetic ganglia and corresponding target organs of the rat: Correlation with density of sympathetic innervation.Proceedings of the National Academy of Sciences of the United States of America. 1983,80: 3513–3516.

    Article  PubMed  CAS  Google Scholar 

  32. Heumann R: Regulation of the synthesis of nerve growth factor.Journal of Experimental Biology. 1987,132:133–150.

    PubMed  CAS  Google Scholar 

  33. Volonte C, Rukenstein A, Loeb DM, Greene LA: Differential inhibition of nerve growth factor responses by purine analogues: Correlation with inhibition of a nerve growth factor-activated protein kinase.Journal of Cell Biology. 1989,109:2395–2403.

    Article  PubMed  CAS  Google Scholar 

  34. Thorpe LW, Stach RW, Hashim D, Marchetti D, Perez-Polo JR: Receptors for NGF on rat spleen mononuclear cells.Journal of Neuroscience Research. 1987,17:128–134.

    Article  PubMed  CAS  Google Scholar 

  35. Otten U, Ehrhard P, Peck R: Nerve growth factor induces growth and differentiation of human B lymphocytes.Proceedings of the National Academy of Sciences of the United States of America. 1989,86:10059–10063.

    Article  PubMed  CAS  Google Scholar 

  36. Chao MV, Bothwell MA, Ross AH, et al: Gene transfer and molecular cloning of the human NGF receptor.Science. 1986,232: 518–521.

    Article  PubMed  CAS  Google Scholar 

  37. Kaplan DR, Hempstead BL, Martin-Zanca D, Chao MV, Parada LF: The trk proto-oncogene product: A signal transducing receptor for nerve growth factor.Science. 1991,252:554–558.

    Article  PubMed  CAS  Google Scholar 

  38. Klein R, Jing S, Nanduri V, O’Rourke E, Barbacid M: The trk proto-oncogene encodes a receptor for nerve growth factor.Cell. 1991,65:189–197.

    Article  PubMed  CAS  Google Scholar 

  39. Schwab ME, Heumann R, Thoenen H: Communication between target organs and nerve cells: Retrograde axonal transport and site of action of nerve growth factor.Cold Spring Harbor Symposia on Quantitative Biology. 1982,46:125–134.

    PubMed  Google Scholar 

  40. Schwab ME, Thoenen H: Retrograde axonal transport. In Lajtha A (ed),Handbook of Neurochemistry (Vol. 5). New York: Plenum Publishing, 1983, 381–404.

    Google Scholar 

  41. Hempstead BL, Martin-Zanca D, Kaplan DR, Parada LF, Chao MV: High-affinity NGF binding requires coexpression of the trk proto-oncogene and the low-affinity NGF receptor.Nature. 1991,350:678–683.

    Article  PubMed  CAS  Google Scholar 

  42. Ibanez CF, Ebendal T, Barbany G, et al: Disruption of the low affinity receptor-binding site in NGF allows neuronal survival and differentiation by binding to the trk gene product.Cell. 1992,69: 329–341.

    Article  PubMed  CAS  Google Scholar 

  43. Wong J, Oblinger MM: NGF rescues substance P expression but not neurofilament or tubulin gene expression in axotomized sensory neurons.Journal of Neuroscience. 1991,17:543–552.

    Google Scholar 

  44. Aloe L, Alleva E, Bohm A, Levi-Montalcini R: Aggressive behavior induces release of nerve growth factor from mouse salivary gland into the bloodstream.Proceedings of the National Academy of Sciences of the United States of America. 1986,83:6184–6187.

    Article  PubMed  CAS  Google Scholar 

  45. Lakshmanan J: Nerve growth factor levels in mouse serum: Variations due to stress.Neurochemical Research. 1987,72:393–397.

    Article  Google Scholar 

  46. Wallace LJ, Partlow LM: α-Adrenergic regulation of secretion of mouse saliva rich in nerve growth factor.Proceedings of the National Academy of Sciences of the United States of America. 1976,75:210–4214.

    Google Scholar 

  47. Taglialatela G, Angelucci L, Ramacci MT, Foreman PJ, Perez-Polo JR:l25I-β-Nerve growth factor binding is reduced in rat brain after stress exposure. 1990,Journal of Neuroscience Research.25: 331–335.

    Article  PubMed  CAS  Google Scholar 

  48. Tocco MD, Contreras ML, Koizumi S, Dickens G, Guroff G: Decreased levels of nerve growth factor receptor on dexametha-sone-treated PC12 cells.Journal of Neuroscience Research. 1988,20:411–119.

    Article  PubMed  CAS  Google Scholar 

  49. Otten U, Baumann JB, Girard J: Stimulation of the pituitary-adrenocortical axis by nerve growth factor.Nature. 1979,252:413–414.

    Article  Google Scholar 

  50. Heumann R, Korsching S, Bandtlow C, Thoenen H: Changes of nerve growth factor synthesis in non-neuronal cells in response to sciatic nerve transection.Journal of Cellular Biology. 1987,704: 1623–1631.

    Article  Google Scholar 

  51. Heumann R, Lindholm D, Bandtlow C, et al: Differential regulation of mRNA encoding nerve growth factor and its receptor in rat sciatic nerve during development, degeneration, and regeneration: Role of macrophages.Proceedings of the National Academy of Sciences of the United States of America. 1987,84:8735–8739.

    Article  PubMed  CAS  Google Scholar 

  52. Lindholm D, Heumann R, Meyer M, Thoenen H: Interleukin-1 regulates synthesis of nerve growth factor in non-neuronal cells of rat sciatic nerve.Nature. 1987,330:658–659.

    Article  PubMed  CAS  Google Scholar 

  53. Lindholm D, Heumann R, Hengerer B, Thoenen H: Interleukin-1 increases stability and transcription of mRNA encoding nerve growth factor in cultured rat fibroblasts.Journal of Biological Chemistry. 1988,263:16348–16351.

    PubMed  CAS  Google Scholar 

  54. Aloe L: Intraocular herpes simplex virus injection in neonatal rats induces sympathetic nerve cell destruction: Effect of nerve growth factor.International Journal of Developmental Neuroscience. 1987,5:357–366.

    Article  PubMed  CAS  Google Scholar 

  55. Dicou E, Nerriere V, Labropoulou V: Naturally occurring antibodies against nerve growth factor in human and rabbit sera: Comparison between control and herpes simplex virus-infected patients.Journal of Neuroimmunology. 1991,54:153–158.

    Article  Google Scholar 

  56. Roizman B, Furlong D: The replication of herpesviruses. In Fraen-kel-Conrat H, Wagner RR (eds),Comprehensive Virology. New York: Plenum Press, 1974, 229–403.

    Google Scholar 

  57. Leib DA, Coen DM, Bogard CL, et al: Immediate-early regulatory gene mutants define different stages in the establishment and reactivation of herpes simplex virus latency.Journal of Virology. 1989,63:759–768.

    PubMed  CAS  Google Scholar 

  58. Cai W, Schaffer PA: Herpes simplex virus Type 1 ICPO plays a critical role in the de novo synthesis of infectious virus following transfection of viral DNA.Journal of Virology. 1989,63:4579–4589.

    PubMed  CAS  Google Scholar 

  59. Mackem S, Roizman B: Structural sequences of the a gene 4, 0, and 27 promoter-regulatory sequences which confer a regulation on chimeric thymidine kinase genes.Journal of Virology. 1982,44:939–949.

    PubMed  CAS  Google Scholar 

  60. Kristie TM, Roizman B: Separation of sequences defining basal expression from those conferring α gene recognition with the regulatory domains of herpes simplex virus 1 α promoters.Proceedings of the National Academy of Sciences of the United States of America. 1984,81:4065–1069.

    Article  PubMed  CAS  Google Scholar 

  61. Gerster T, Roeder RG: A herpesvirus transactivating protein interacts with transcription factor OTF-1 and other cellular proteins.Proceedings of the National Academy of Sciences of the United States of America. 1988,85:6347–6351.

    Article  PubMed  CAS  Google Scholar 

  62. Kristie TM, Roizman B: Host cell proteins bind to the cis-acting site required for virion-mediated induction of herpes simplex virus 1 α genes.Proceedings of the National Academy of Sciences of the United States of America. 1987,84:71–75.

    Article  PubMed  CAS  Google Scholar 

  63. O’Hare P, Goding CR: Herpes simplex virus regulatory elements and the immunoglobulin octamer domain bind a common factor and are both targets for virion transactivation.Cell. 1988,52: 435–445.

    Article  PubMed  CAS  Google Scholar 

  64. McKnight JLC, Kristie TM, Roizman B: Binding of the virion protein mediating α gene induction in herpes simplex virus-infected cells to its cis site requires cellular proteins.Proceedings of the National Academy of Sciences of the United States of America. 1987,84:7061–7065.

    Article  PubMed  CAS  Google Scholar 

  65. O’Hare P, Goding CR, Haigh A: Direct combinatorial interaction between a herpes simplex virus regulatory protein and a cellular octamer-binding factor mediates specific induction of virus immediate-early gene expression.EMBO Journal. 1988,7:4231–4238.

    PubMed  CAS  Google Scholar 

  66. Preston CM, Frame MC, Campbell MEM: A complex formed between cell components and a herpes simplex virus structural polypeptide binds to a viral immediate-early gene regulatory DNA sequence.Cell. 1988,52:425–434.

    Article  PubMed  CAS  Google Scholar 

  67. Vahlne A, Lycke E: Herpes simplex virus infection ofin vitro cultured neuronal cells (Mouse neuroblastoma C 1300 cells).Journal of General Virology. 1978,59:321–332.

    Article  Google Scholar 

  68. Kemp LM, Latchman DS: Regulated transcription of herpes simplex virus immediate-early genes in neuroblastoma cells.Virology. 1989,171:607–610.

    Article  PubMed  CAS  Google Scholar 

  69. Wheatley SC, Kemp LM, Wood JN, Latchman DS: Cell lines derived from dorsal root ganglion neurons are non-permissive for HSV and express only the latency-associated transcript following infection.Experimental Cell Research. 1990,190:243–246.

    Article  PubMed  CAS  Google Scholar 

  70. Kemp LM, Dent CL, Latchman DS: Octamer motif mediates transcriptional repression of HSV immediate-early genes and octamer-containing cellular promoters in neuronal cells.Neuron. 1990,4: 215–222.

    Article  PubMed  CAS  Google Scholar 

  71. Lillycrop KA, Dent CL, Wheatley SC, et al: The octamer-binding protein Oct-2 represses HSV immediate-early genes in cell lines derived from latently infectible sensory neurons.Neuron. 1991,7: 381–390.

    Article  PubMed  CAS  Google Scholar 

  72. Liang P, Pardee AB: Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction.Science. 1992,257:967–971.

    Article  PubMed  CAS  Google Scholar 

  73. Wood JN, Lillycrop KA, Dent CL, et al: Regulation of expression of the neuronal POU protein Oct-2 by nerve growth factor.Journal of Biological Chemistry. 1992,267:17787–17791.

    PubMed  CAS  Google Scholar 

  74. Jang KL, Pulverer B, Woodgett JR, Latchman DS: Activation of the cellular transcription factor AP-1 in herpes simplex virus infected cells is dependent on the viral immediate-early protein ICPO.Nucleic Acids Research. 1991,19:4879–4883.

    Article  PubMed  CAS  Google Scholar 

  75. Kontny E, Kvanta A, Fredholm BB: Activation of protein kinase C and elevation of cAMP interact synergistically to raise c-Fos and AP-1 activity in Jurkat cells.European Journal of Pharmacology. 1992,227:333–338.

    Article  PubMed  CAS  Google Scholar 

  76. Rincon M, Tugores A, de Landazuri MO, Lopez-Botet M: Costim-ulation of cAMP and protein kinase C pathways inhibits the CD3-dependent T cell activation and leads to a persistent expression of the AP-1 transcription factor.Cellular Immunology. 1993,149: 343–356.

    Article  PubMed  CAS  Google Scholar 

  77. Serkkola E, Hurme M: Synergism between protein kinase C and cAMP-dependent pathways in the expression of the interleukin-1 beta gene is mediated via the activator protein-1 (AP-1) enhancer activity.European Journal of Biochemistry. 1993,275:243–249.

    Article  Google Scholar 

  78. Wheatley SC, Dent CL, Wood JN, Latchman DS: Elevation of cyclic AMP levels in cell lines derived from latently infectible sensory neurons increases their permissivity for herpes virus infection by activating the viral immediate-early 1 gene promoter.Molecular Brain Research. 1992,12:149–154.

    Article  PubMed  CAS  Google Scholar 

  79. Greene LA, Drexler SA, Connolly JL, Rukenstein A, Green SH: Selective inhibition of responses to nerve growth factor and of microtubule-associated protein phosphorylation by activators of adenylate cyclase.Journal of Cell Biology. 1986,705:1967–1978.

    Article  Google Scholar 

  80. Petkova I, Milkov V: Stress-induced changes in the cyclic nucleotide concentrations and phosphorylase activity in the myocardium.Acta Physiologica et Pharmacologica Bulgarica. 1991,77: 129–134.

    Google Scholar 

  81. Goldman JE, Abramson B: Cyclic AMP-induced shape changes of astrocytes are accompanied by rapid depolymerization of actin.Brain Research. 1990,528:189–196.

    Article  PubMed  CAS  Google Scholar 

  82. Chakraborti S, Batabyal SK: Adrenocortical activity and plasma cAMP levels of humans under high altitude stress.Clinica Chimica Acta. 1989,184:329–331.

    Article  CAS  Google Scholar 

  83. Hadden JW: Cyclic nucleotides in lymphocyte function.Annals of the New York Academy of Sciences. 1975,256:352–364.

    Article  PubMed  CAS  Google Scholar 

  84. Hadden JW, Coffey RG: Cyclic nucleotides in mitogen-induced lymphocyte proliferation.Immunology Today. 1982,5:299–304.

    Article  Google Scholar 

  85. Rabizadeh S, Oh J, Zhong L, et al: Induction of apoptosis by the low-affinity NGF receptor.Science. 1993,261:345–348.

    Article  PubMed  CAS  Google Scholar 

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  1. Division of Behavioral Medicine and Oncology, Pittsburgh Cancer Institute, University of Pittsburgh, 3600 Forbes Avenue, Suite 405, 15213, Pittsburgh, PA

    Frank J. Jenkins & Andrew Baum

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  1. Frank J. Jenkins
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Jenkins, F.J., Baum, A. Stress and reactivation of latent herpes simplex virus: A fusion of behavioral medicine and molecular biology. Ann Behav Med 17, 116–123 (1995). https://doi.org/10.1007/BF02895060

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