Effect of Apolipoprotein E on the Cerebral Load of Latent Herpes Simplex Virus Type 1 DNA

  1. Burgos, Javier S. 1
  2. Ramirez, Carlos 1
  3. Sastre, Isabel 1
  4. Valdivieso, Fernando 1
  1. 1 Centro de Biología Molecular Severo Ochoa
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    Centro de Biología Molecular Severo Ochoa

    Madrid, España

    ROR https://ror.org/03v9e8t09

Revista:
Journal of Virology

ISSN: 0022-538X,  1098-5514

Año de publicación: 2006

Volumen: 80

Número: 11

Páginas: 5383-5387

Tipo: Artículo

DOI: 10.1128/JVI.00006-06 GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: Journal of Virology

Objetivos de desarrollo sostenible

Resumen

Herpes simplex virus type 1 (HSV-1) is neurotropic and enters a latent state lasting the lifetime of the host. This pathogen has recently been proposed as a risk factor for Alzheimer's disease (AD) in conjunction with apolipoprotein E4 (ApoE4). In a murine acute infection model, we showed that viral neuroinvasiveness depends directly on the overall ApoE dosage and especially on the presence of isoform ApoE4. If an interaction between ApoE and HSV-1 is involved in AD, it may occur during latency rather than during acute infection. Certainly, ApoE plays an important role in late-onset AD, i.e., at a time in life when the majority of people harbor HSV-1 in their nervous system. In the present work, wild-type, APOE knockout, APOE3, and APOE4 transgenic mice were used to analyze the influence of the ApoE profile on the levels of latent virus DNA. The knockout mice had significantly lower concentrations of the virus in the nervous system than the wild-type mice, while the APOE4 mice had very high levels in the brain compared to the APOE3 animals. ApoE4 seems to facilitate HSV-1 latency in the brain much more so than ApoE3. The APOE dosage correlated directly with the HSV-1 DNA concentration in the brain, strengthening the hypothesis that HSV-1, together with ApoE, might be involved in AD.

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Información de financiación

This work was supported by a grant from the Obra Social Caja Madrid to the Asociación de Familiares de Enfermos de Alzheimer and by an institutional grant from the Fundación Areces to the Centro de Biología Molecular Severo Ochoa. We thank F. Mayor for his continuous encouragement and help and L. Carrasco for providing the HSV-1 KOS strain.

Financiadores

  • Obra Social Caja Madrid Spain
  • Fundación Areces Spain

Referencias bibliográficas

  • 1. Ball, M. J.1986. Herpesvirus in the hippocampus as a cause of Alzheimer's disease. Arch. Neurol.43:313.
  • 2. Ball, M. J.1982. Limbic predilection in Alzheimer dementia: is reactivated herpesvirus involved? Can. J. Neurol. Sci.9:303-306.
  • 3. Baringer, J. R., and P. Pisani.1994. Herpes simplex virus genomes in human nervous system tissue analyzed by polymerase chain reaction. Ann. Neurol.36:823-829.
  • 4. Bretsky, P., J. M. Guralnik, L. Launer, M. Albert, and T. E. Seeman.2003. The role of APOE-epsilon4 in longitudinal cognitive decline: MacArthur Studies of Successful Aging. Neurology60:1077-1081.
  • 5. Burgos, J. S., C. Ramirez, F. Guzman-Sanchez, J. M. Alfaro, I. Sastre, and F. Valdivieso.2006. Hematogenous vertical transmission of herpes simplex virus type 1 in mice. J. Virol.80:2823-2831.
  • 6. Burgos, J. S., C. Ramirez, I. Sastre, J. M. Alfaro, and F. Valdivieso.2005. Herpes simplex virus type 1 infection via the bloodstream with apolipoprotein E dependence in the gonads is influenced by gender. J. Virol.79:1605-1612.
  • 7. Burgos, J. S., C. Ramirez, I. Sastre, M. J. Bullido, and F. Valdivieso.2003. ApoE4 is more efficient than E3 in brain access by herpes simplex virus type 1. Neuroreport14:1825-1827.
  • 8. Burgos, J. S., C. Ramirez, I. Sastre, M. J. Bullido, and F. Valdivieso.2002. Involvement of apolipoprotein E in the hematogenous route of herpes simplex virus type 1 to the central nervous system. J. Virol.76:12394-12398.
  • 9. Burgos, J. S., C. Ramirez, R. Tenorio, I. Sastre, and M. J. Bullido.2002. Influence of reagents formulation on real-time PCR parameters. Mol. Cell. Probes16:257-260.
  • 10. Corder, E. H., A. M. Saunders, W. J. Strittmatter, D. E. Schmechel, P. C. Gaskell, G. W. Small, A. D. Roses, J. L. Haines, and M. A. Pericak-Vance.1993. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science261:921-923.
  • 11. Deatly, A. M., J. G. Spivack, E. Lavi, D. R. O'Boyle II, and N. W. Fraser.1988. Latent herpes simplex virus type 1 transcripts in peripheral and central nervous system tissues of mice map to similar regions of the viral genome. J. Virol.62:749-756.
  • 12. DeMattos, R. B., L. K. Curtiss, and D. L. Williams.1998. A minimally lipidated form of cell-derived apolipoprotein E exhibits isoform-specific stimulation of neurite outgrowth in the absence of exogenous lipids or lipoproteins. J. Biol. Chem.273:4206-4212.
  • 13. Farrer, L. A., L. A. Cupples, J. L. Haines, B. Hyman, W. A. Kukull, R. Mayeux, R. H. Myers, M. A. Pericak-Vance, N. Risch, C. M. van Duijn, et al.1997. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. JAMA278:1349-1356.
  • 14. Fraser, N. W., W. C. Lawrence, Z. Wroblewska, D. H. Gilden, and H. Koprowski.1981. Herpes simplex type 1 DNA in human brain tissue. Proc. Natl. Acad. Sci. USA78:6461-6465.
  • 15. Fraser, N. W., and T. Valyi-Nagy.1993. Viral, neuronal and immune factors which may influence herpes simplex virus (HSV) latency and reactivation. Microb. Pathog.15:83-91.
  • 16. Fukumoto, H., M. Tennis, J. J. Locascio, B. T. Hyman, J. H. Growdon, and M. C. Irizarry.2003. Age but not diagnosis is the main predictor of plasma amyloid beta-protein levels. Arch. Neurol.60:958-964.
  • 17. Gerdes, L. U.2003. The common polymorphism of apolipoprotein E: geographical aspects and new pathophysiological relations. Clin. Chem. Lab. Med.41:628-631.
  • 18. Gesser, R. M., T. Valyi-Nagy, S. M. Altschuler, and N. W. Fraser.1994. Oral-oesophageal inoculation of mice with herpes simplex virus type 1 causes latent infection of the vagal sensory ganglia (nodose ganglia). J. Gen. Virol.75:2379-2386.
  • 19. Hardy, J.2003. Alzheimer's disease: genetic evidence points to a single pathogenesis. Ann. Neurol.54:143-144.
  • 20. Hill, T. J., H. J. Field, and W. A. Blyth.1975. Acute and recurrent infection with herpes simplex virus in the mouse: a model for studying latency and recurrent disease. J. Gen. Virol.28:341-353.
  • 21. Itabashi, S., H. Arai, T. Matsui, S. Higuchi, and H. Sasaki.1997. Herpes simplex virus and risk of Alzheimer's disease. Lancet349:1102.
  • 22. Itzhaki, R.2004. Herpes simplex virus type 1, apolipoprotein E and Alzheimer' disease. Herpes11(Suppl. 2):77A-82A.
  • 23. Itzhaki, R. F., C. B. Dobson, and M. A. Wozniak.2004. Herpes simplex virus type 1 and Alzheimer's disease. Ann. Neurol.55:299-300. (Author's Reply, 55:300-301.)
  • 24. Itzhaki, R. F., and W. R. Lin.1998. Herpes simplex virus type I in brain and the type 4 allele of the apolipoprotein E gene are a combined risk factor for Alzheimer's disease. Biochem. Soc. Trans.26:273-277.
  • 25. Itzhaki, R. F., W. R. Lin, D. Shang, G. K. Wilcock, B. Faragher, and G. A. Jamieson.1997. Herpes simplex virus type 1 in brain and risk of Alzheimer's disease. Lancet349:241-244.
  • 26. Jamieson, G. A., N. J. Maitland, G. K. Wilcock, J. Craske, and R. F. Itzhaki.1991. Latent herpes simplex virus type 1 in normal and Alzheimer's disease brains. J. Med. Virol.33:224-227.
  • 27. Jamieson, G. A., N. J. Maitland, G. K. Wilcock, C. M. Yates, and R. F. Itzhaki.1992. Herpes simplex virus type 1 DNA is present in specific regions of brain from aged people with and without senile dementia of the Alzheimer type. J. Pathol.167:365-368.
  • 28. Jarvik, G. P., E. M. Wijsman, W. A. Kukull, G. D. Schellenberg, C. Yu, and E. B. Larson.1995. Interactions of apolipoprotein E genotype, total cholesterol level, age, and sex in prediction of Alzheimer's disease: a case-control study. Neurology45:1092-1096.
  • 29. Johnson, R. P.1998. Viral infections of the nervous system, 2nd ed., p. 133-168. Lippincott Raven, Philadelphia, Pa.
  • 30. Knouff, C., M. E. Hinsdale, H. Mezdour, M. K. Altenburg, M. Watanabe, S. H. Quarfordt, P. M. Sullivan, and N. Maeda.1999. Apo E structure determines VLDL clearance and atherosclerosis risk in mice. J. Clin. Investig.103:1579-1586.
  • 31. Levy-Lahad, E., D. Tsuang, and T. D. Bird.1998. Recent advances in the genetics of Alzheimer's disease. J. Geriatr. Psychiatry Neurol.11:42-54.
  • 32. Mahley, R. W.1988. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science240:622-630.
  • 33. Miller, C. S., R. J. Danaher, and R. J. Jacob.1998. Molecular aspects of herpes simplex virus I latency, reactivation, and recurrence. Crit. Rev. Oral Biol. Med.9:541-562.
  • 34. Mori, I., Y. Kimura, H. Naiki, R. Matsubara, T. Takeuchi, T. Yokochi, and Y. Nishiyama.2004. Reactivation of HSV-1 in the brain of patients with familial Alzheimer's disease. J. Med. Virol.73:605-611.
  • 35. Mufson, E. J., M. D. Ikonomovic, S. D. Styren, S. E. Counts, J. Wuu, S. Leurgans, D. A. Bennett, E. J. Cochran, and S. T. DeKosky.2003. Preservation of brain nerve growth factor in mild cognitive impairment and Alzheimer disease. Arch. Neurol.60:1143-1148.
  • 36. Nahmias, A. J., F. K. Lee, and S. Beckman-Nahmias.1990. Sero-epidemiological and -sociological patterns of herpes simplex virus infection in the world. Scand. J. Infect. Dis. Suppl.69:19-36.
  • 37. Nathoo, N., R. Chetty, J. R. van Dellen, and G. H. Barnett.2003. Genetic vulnerability following traumatic brain injury: the role of apolipoprotein E. Mol. Pathol.56:132-136.
  • 38. Pandav, R., H. H. Dodge, S. T. DeKosky, and M. Ganguli.2003. Blood pressure and cognitive impairment in India and the United States: a cross-national epidemiological study. Arch. Neurol.60:1123-1128.
  • 39. Piedrahita, J. A., S. H. Zhang, J. R. Hagaman, P. M. Oliver, and N. Maeda.1992. Generation of mice carrying a mutant apolipoprotein E gene inactivated by gene targeting in embryonic stem cells. Proc. Natl. Acad. Sci. USA89:4471-4475.
  • 40. Poirier, J., A. Minnich, and J. Davignon.1995. Apolipoprotein E, synaptic plasticity and Alzheimer's disease. Ann. Med.27:663-670.
  • 41. Roberts, J. S., S. A. LaRusse, H. Katzen, P. J. Whitehouse, M. Barber, S. G. Post, N. Relkin, K. Quaid, R. H. Pietrzak, L. A. Cupples, L. A. Farrer, T. Brown, and R. C. Green.2003. Reasons for seeking genetic susceptibility testing among first-degree relatives of people with Alzheimer disease. Alzheimer Dis. Assoc. Disord.17:86-93.
  • 42. Rocchi, A., S. Pellegrini, G. Siciliano, and L. Murri.2003. Causative and susceptibility genes for Alzheimer's disease: a review. Brain Res. Bull.61:1-24.
  • 43. Roses, A. D.1996. Apolipoprotein E alleles as risk factors in Alzheimer's disease. Annu. Rev. Med.47:387-400.
  • 44. Rubinsztein, D. C., and D. F. Easton.1999. Apolipoprotein E genetic variation and Alzheimer's disease. A meta-analysis. Dement. Geriatr. Cogn. Disord.10:199-209.
  • 45. Saunders, A. M., W. J. Strittmatter, D. Schmechel, P. H. George-Hyslop, M. A. Pericak-Vance, S. H. Joo, B. L. Rosi, J. F. Gusella, D. R. Crapper-MacLachlan, M. J. Alberts, et al.1993. Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease. Neurology43:1467-1472.
  • 46. Sawtell, N. M., D. K. Poon, C. S. Tansky, and R. L. Thompson.1998. The latent herpes simplex virus type 1 genome copy number in individual neurons is virus strain specific and correlates with reactivation. J. Virol.72:5343-5350.
  • 47. Sequiera, L. W., L. C. Jennings, L. H. Carrasco, M. A. Lord, A. Curry, and R. N. Sutton.1979. Detection of herpes-simplex viral genome in brain tissue. Lancetii:609-612.
  • 48. Strittmatter, W. J., and A. D. Roses.1995. Apolipoprotein E and Alzheimer disease. Proc. Natl. Acad. Sci. USA92:4725-4727.
  • 49. Sullivan, P. M., H. Mezdour, Y. Aratani, C. Knouff, J. Najib, R. L. Reddick, S. H. Quarfordt, and N. Maeda.1997. Targeted replacement of the mouse apolipoprotein E gene with the common human APOE3 allele enhances diet-induced hypercholesterolemia and atherosclerosis. J. Biol. Chem.272:17972-17980.
  • 50. Vega, G. L., M. F. Weiner, A. M. Lipton, K. Von Bergmann, D. Lutjohann, C. Moore, and D. Svetlik.2003. Reduction in levels of 24S-hydroxycholesterol by statin treatment in patients with Alzheimer disease. Arch. Neurol.60:510-515.
  • 51. Warren, K. G., S. M. Brown, Z. Wroblewska, D. Gilden, H. Koprowski, and J. Subak-Sharpe.1978. Isolation of latent herpes simplex virus from the superior cervical and vagus ganglions of human beings. N. Engl. J. Med.298:1068-1069.
  • 52. Weisgraber, K. H., and R. W. Mahley.1996. Human apolipoprotein E: the Alzheimer's disease connection. FASEB J.10:1485-1494.
  • 53. Whitley, R. J., and B. Roizman.2001. Herpes simplex virus infections. Lancet357:1513-1518.