Herpes simplex virus interferes with amyloid precursor protein processing

详细信息    查看全文

• 作者：Suzanne J Shipley (1) <br> Edward T Parkin (2) <br> Ruth F Itzhaki (1) <br> Curtis B Dobson (1) <br>
• 刊名：BMC Microbiology
• 出版年：2005
• 出版时间：December 2005
• 年：2005
• 卷：5
• 期：1
• 全文大小：1090KB
• 参考文献：1. Raiha I, Kaprio J, Koskenvuo M, Rajala T, Sourander L: Alzheimer's disease in Finnish twins. / Lancet 1996, 347:573-78. CrossRef <br> 2. Selkoe DJ: Deciphering the genesis and fate of amyloid beta-protein yields novel therapies for Alzheimer disease. / J Clin Invest 2002, 110:1375-381. <br> 3. Itzhaki RF, Lin WR, Shang D, Wilcock GK, Faragher B, Jamieson GA: Herpes simplex virus type 1 in brain and risk of Alzheimer's disease. / Lancet 1997, 349:241-44. CrossRef <br> 4. Lin WR, Graham J, MacGowan SM, Wilcock GK, Itzhaki RF: Alzheimer's disease, herpes virus in brain, apolipoprotein E4 and herpes labialis. / Alzheimer's Reports 1998, 1:173-78. <br> 5. Dobson CB, Wozniak MA, Itzhaki RF: Do infectious agents play a role in dementia? / Trends Microbiol 2003, 11:312-17. CrossRef <br> 6. Holmes C, El-Okl M, Williams AL, Cunningham C, Wilcockson D, Perry VH: Systemic infection, interleukin 1beta, and cognitive decline in Alzheimer's disease. / J Neurol Neurosurg Psychiatry 2003, 74:788-89. CrossRef <br> 7. Strandberg TE, Pitkala KH, Linnavuori KH, Tilvis RS: Impact of viral and bacterial burden on cognitive impairment in elderly persons with cardiovascular diseases. / Stroke 2003, 34:2126-131. CrossRef <br> 8. Jamieson GA, Maitland NJ, Wilcock GK, Yates CM, Itzhaki RF: 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 1992, 167:365-68. CrossRef <br> 9. Dickerson FB, Boronow JJ, Stallings C, Origoni AE, Cole S, Krivogorsky B, Yolken RH: Infection with herpes simplex virus type 1 is associated with cognitive deficits in bipolar disorder. / Biol Psychiatry 2004, 55:588-93. biopsych.2003.10.008">CrossRef <br> 10. Combrinck MI, Perry VH, Cunningham C: Peripheral infection evokes exaggerated sickness behaviour in pre-clinical murine prion disease. / Neuroscience 2002, 112:7-1. CrossRef <br> 11. Cribbs DH, Azizeh BY, Cotman CW, LaFerla FM: Fibril formation and neurotoxicity by a herpes simplex virus glycoprotein B fragment with homology to the Alzheimer's A beta peptide. / Biochemistry 2000, 39:5988-994. bi000029f">CrossRef <br> 12. Roberts GW, Gentleman SM, Lynch A, Graham DI: beta A4 amyloid protein deposition in brain after head trauma. / Lancet 1991, 338:1422-423. CrossRef <br> 13. Popa-Wagner A, Schroder E, Walker LC, Kessler C: beta-Amyloid precursor protein and ss-amyloid peptide immunoreactivity in the rat brain after middle cerebral artery occlusion: effect of age. / Stroke 1998, 29:2196-202. <br> 14. Esiri MM, Biddolph SC, Morris CS: Prevalence of Alzheimer plaques in AIDS. / J Neurol Neurosurg Psychiatry 1998, 65:29-3. CrossRef <br> 15. Kummer C, Wehner S, Quast T, Werner S, Herzog V: Expression and potential function of beta-amyloid precursor proteins during cutaneous wound repair. / Exp Cell Res 2002, 280:222-32. CrossRef <br> 16. Wiley CA, Achim CL, Hammond R, Love S, Masliah E, Radhakrishnan L, Sanders V, Wang G: Damage and repair of DNA in HIV encephalitis. / J Neuropathol Exp Neurol 2000, 59:955-65. <br> 17. Satpute-Krishnan P, DeGiorgis JA, Bearer EL: Fast anterograde transport of herpes simplex virus: role for the amyloid precursor protein of alzheimer's disease. / Aging Cell 2003, 2:305-18. CrossRef <br> 18. Matis J, Kudelova M: Early shutoff of host protein synthesis in cells infected with herpes simplex viruses. / Acta Virol 2001, 45:269-77. <br> 19. Roizman B, Sears A: Herpes simplex viruses and their replication. / Fundamental virology / (Edited by: Fields B, Knipe D and Howley P). Philadelphia, Lippincott-Raven 1995, 1043-107. <br> 20. Lin WR, Wozniak MA, Cooper RJ, Wilcock GK, Itzhaki RF: Herpesviruses in brain and Alzheimer's disease. / J Pathol 2002, 197:395-02. CrossRef <br> 21. Wozniak MA, Shipley SJ, Combrinck M, Wilcock GK, Itzhaki RF: Productive herpes simplex virus in brain of elderly normal subjects and Alzheimer's disease patients. / J Med Virol 2005, 75:300-06. CrossRef <br> 22. Little CS, Hammond CJ, MacIntyre A, Balin BJ, Appelt DM: Chlamydia pneumoniae induces Alzheimer-like amyloid plaques in brains of BALB/c mice. / Neurobiol Aging 2004, 25:419-29. CrossRef <br>
• 作者单位：Suzanne J Shipley (1) <br> Edward T Parkin (2) <br> Ruth F Itzhaki (1) <br> Curtis B Dobson (1) <br><br>1. Faculty of Life Sciences, University of Manchester, Moffat Building, M60 1QD, Manchester, UK <br> 2. School of Biochemistry and Molecular Biology, University of Leeds, LS2 9JT, Leeds, W. Yorks, UK <br>
• ISSN：1471-2180

文摘

Background The early events underlying Alzheimer's disease (AD) remain uncertain, although environmental factors may be involved. Work in this laboratory has shown that the combination of herpes simplex virus type 1 (HSV1) in brain and carriage of the APOE-ε4 allele of the APOE gene strongly increases the risk of developing AD. The development of AD is thought to involve abnormal aggregation or deposition of a 39-3 amino acid protein - β amyloid (Aβ) - within the brain. This is cleaved from the much larger transmembranal protein 'amyloid precursor protein' (APP). Any agent able to interfere directly with Aβ or APP metabolism may therefore have the capacity to contribute towards AD. One recent report showed that certain HSV1 glycoprotein peptides may aggregate like Aβ; a second study described a role for APP in transport of virus in squid axons. However to date the effects of acute herpesvirus infection on metabolism of APP in human neuronal-type cells have not been investigated. In order to find if HSV1 directly affects APP and its degradation, we have examined this protein from human neuroblastoma cells (normal and transfected with APP 695) infected with the virus, using Western blotting. Results We have found that acute HSV1 (and also HSV2) infection rapidly reduces full length APP levels - as might be expected - yet surprisingly markedly increases levels of a novel C-terminal fragment of APP of about 55 kDa. This band was not increased in cells treated with the protein synthesis inhibitor cycloheximide Conclusion Herpes virus infection leads to rapid loss of full length APP from cells, yet also causes increased levels of a novel 55 kDa C-terminal APP fragment. These data suggest that infection can directly alter the processing of a transmembranal protein intimately linked to the aetiology of AD.