Connections between herpes simplex virus type 1 and Alzheimer’s disease pathogenesis

Current Alzheimer Research

Volumn 13, Issue 9, 2016, Pages 996-1005

  McNamara, James ^a   Ann Murray, Teresa ^b  

^a William Carey University   (United States)

^b LOUISIANA TECH UNIVERSITY   (United States)

Author keywords

Alzheimer s disease; Beta amyloid; Cell cycle reentry; Herpes simplex virus; HSV1; Tau pathology

Indexed keywords

AMYLOID BETA PROTEIN; ARIPIPRAZOLE; DONEPEZIL; OLANZAPINE; TAU PROTEIN;

ALZHEIMER DISEASE; ARTICLE; AUTOPHAGY; BRAIN INFECTION; CELL CYCLE; DEGENERATIVE DISEASE; DISEASE ASSOCIATION; DISEASE COURSE; ENVIRONMENTAL FACTOR; EPIGENETICS; HERPES SIMPLEX; HERPES SIMPLEX VIRUS 1; HERPES SIMPLEX VIRUS 1 INFECTION; HUMAN; INFECTION; INNATE IMMUNITY; MEDICAL RESEARCH; NERVOUS SYSTEM INFLAMMATION; NEUROFIBRILLARY TANGLE; NEUROPATHOLOGY; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; BRAIN; COMPLICATION; HUMAN ALPHAHERPESVIRUS 1; PATHOLOGY; PATHOPHYSIOLOGY; VIROLOGY;

ALZHEIMER DISEASE; BRAIN; HERPES SIMPLEX; HERPESVIRUS 1, HUMAN; HUMANS;

EID: 84981555597     PISSN: 15672050     EISSN: 18755828     Source Type: Journal    
DOI: 10.2174/1567205013666160314150136     Document Type: Article

References (113)

1. Pozo AS, Frosch MP, Masliah E, Hyman BT. Neuropathological alterations in Alzheimer’s disease. Cold Spring Harb Perspect Med 1(1): a006189 (2011).
2. Minati L, Edgington T, Bruzzone MG, Giccone G. Current concepts in Alzheimer’s disease: A multidisciplinary review. Am J Alzheimers Dis Other Dement 24: 95-121 (2009).
3. Ball MJ, Lukiw WJ, Kammerman EM, Hill JD. Intracerebral propagation of Alzheimer’s Disease: Strengthening evidence of a Herpes Simplex etiology. Alzheimers Dement 9: 169-75 (2013).
4. Itzhaki RF, Wozniak MA, Appelt DM, Balin BJ. Infiltration of the brain by pathogens causes Alzheimer’s disease. Neurobiol Aging 25: 619-27 (2004).
5. Itzhaki RF, Cosby SL, Wozniak MA. Herpes simplex virus type 1 and Alzheimer’s disease: The autophagy connection. J Neurovirol 14: 1-4 (2008).
6. Lin WR, Wozniak MA, Cooper RJ, Wilcock GK, Itzhaki RF. Herpesviruses in brain and Alzheimer’s disease. J Pathol 197: 395-402 (2002).
7. Honjo K, van Reekum R, Verhoeff NPLG. Alzheimer’s disease and infection: Do infectious agents contribute to the progression of Alzheimer’s disease? Alzheimers Dement 5(4): 348-60 (2009).
8. McShea A, Lee HG, Petersen R, Cassadesus G, Vincent I, Linford N, et al. Cell Cycle re-entry mediates Alzheimer’s disease-type changes. Biochim Biophys Acta 1772(4): 467-72 (2007).
9. Liu L, Drouet V, Wu JW, Witter MP, Small SA, C. Clelland, Duff K. Trans synaptic spread of Tau pathology in vivo. PLoS One 7: 313-21 (2012).
10. de Calignon A, Polydoro M, William C, Adamowicz DH, Ashe K, Carlson GA, et al. Propagation of tau pathology in a model of early alzheimer’s disease. Neuron 73: 685-97 (2012).
11. Harris JA, Devidze N, Verret L, Masliah E, Mucke L. Transsynaptic progression of Amyloid beta induced neuronal dysfunction within the entorhinal-hippocampal network. Neuron 68: 428-41 (2010).
12. Duara R, Lowenstein DA, Shen Q, Barker W, Greig MT, Varon D, et al. Regional patterns of atrophy on MRI in Alzheimer’s disease: Neuropsychological features in the ADNI cohort. Adv Alzheimers Dis 2: 135-47 (2013).
13. Foss B, Diamond MI. Prion like mechanisms in neurodegenerative diseases. Nat Rev Neurosci 11: 155-9 (2010).
14. Alzheimer’s disease standard prescriptions. Alzheimer’s Association, http://www.alz.org/alzheimers_disease_standard_prescriptions.asp. Accessed 10 July 2014. (2014).
15. Ittner LM and Gotz J. Amyloid-beta and tau: A toxic pas de deux in Alzheimer’s disease. Nat Rev Neurosci 12: 67-73 (2011).
16. Wakabayashi K, Tanji K, Odagiri S, Miki Y, Mori F, Takahashi H. The Lewy body in Parkinson’s disease and related neurodegenerative disorders. Mol Neurobiol 47: 495-508 (2013).
17. Higashi S, Iseki E, Yamamoto R, Minegishi M, Hino H, Fujisawa K, et al. Concurrence of TDP-43, tau, and alpha-synuclein pathology in brains of AD and dementia with Lewy bodies. Brain Res 1184: 284-94 (2007).
18. Robinson SR, Dobson C, Lyons J. Challenges and directions for the pathogen hypothesis of Alzheimer’s disease. Neurobiol Aging 25(5): 629-637 (2004).
19. Corsellis JAN. The transmissibility of dementia. Br Med Bull 42(1): 111-4 (1986).
20. Karasneh GA, Shukla D. Herpes simplex virus infects most cell types in vitro: Clues to its success. Virol J 8: 481-90 (2011).
21. Smith J, Robinson NJ. Age-specific prevalence of infection with Herpes Simplex virus types 2 and 1: A global review. J Infect Dis 186: 3-28 (2002).
22. Piacentini R, di Chiara G, Li Puma DD, Ripoli C, Palamara AT, and Grassi C. HSV1 and Alzheimer’s disease: More than a hypothesis. Front Pharmacol 5: 1-8 (2014).
23. Panegyres PK. The amyloid precursor protein gene: A neuropeptide with diverse functions in the central nervous system. Neuropeptides 31: 523-35 (1997).
24. Santana S, Recuero M, Bullido MJ, Valdivieso F, Aldudo J. Herpes simplex virus type 1 induces the accumulation of intracellular β-amyloid in autophagic compartments and the inhibition of the nonamyloidogenic pathway in human neuroblastoma cells. Neurobiol Aging 33: 43019-33 (2012).
25. Ill-Raga G, Palomer E, Wozniak MA, Ramos-Fernandez E, Itzhaki RF, Munoz FJ. Activation of PKR causes amyloid accumulation via de-repression of BACE1 expression. PLoS One 6: 21456-65 (2011).
26. Serrano-Pozo A, Mielke ML, Gomex-Isla T,. Betensky RA, Growdon JH, Frosch MP, et al. Reactive glia not only associates with plaques but also parallels tangles in Alzheimer’s Disease. Am J Pathol 179: 1373-84 (2011).
27. Lynch MA. Long-term potentiation and memory. Physiol Rev 84: 87-136 (2004).
28. Walsh DM, Klyubin I, Fadeeva JV, Rowan MJ, Selkoe DJ. Amyloid-β oligomers: Their production, toxicity and therapeutic inhibition. Biochem Soc Trans 30(4): 552-7 (2002).
29. Li C, Zhao R, Gao K, Wei Z, Yin MY, Lau LT, et al. Astrocytes: Implications for neuroinflammatory pathogenesis of Alzheimer’s disease. Curr Alzheimer Res 8: 67-80 (2011).
30. Enquist LW, Husak PJ, Banfield BW, Smith GA. Infection and spread of alphaherpesviruses in the nervous system. Adv Virus Res 51: 237-47 (1998).
31. Haines DE. Fundamental Neuroscience for Basic and Clinical Applications 4th ed. Philadelphia: Elsevier (2012).
32. Becker Y. HSV-1 brain infection by the olfactory nerve route and virus latency and reactivation may cause learning and behavioral deficiencies and violence in children and adults: A point of view. Virus Genes 10: 217-26 (1995).
33. Mori I, Nishiyama Y, Yokochi T, Kimura Y. Olfactory transmission of neurotropic viruses. J Neurovirol 11(2): 129-37 (2005).
34. Barnett EM, Cassell MD, Perlman S. Two neurotropic viruses, herpes simplex virus type 1 and mouse hepatitis virus, spread along different neural pathways from the olfactory bulb. Neuroscience 57: 1007-25 (1993).
35. Curanovic D, Enquist L. Directional transneuronal spread of alpha herpesvirus infection. Future Virol 4(6): 591-610 (2009).
36. De Chiara G, Marcocci ME, Sgarbanti R, Civitelli L, Ripoli C, Piacentini R, et al. Infectious agents and neurodegeneration. Mol Neurobiol 46(3): 614-38 (2012).
37. Radtke K, Kieneke D, Wolfstein A, Michael K, Steffen W, Scholz T, et al. Plus-and minus-end directed microtubule motors bind simultaneously to herpes simplex virus capsids using different inner tegument structures. PLoS Pathog 6(7): 991-1010 (2010).
38. Douglas MW, Diefenbach, RJ, Homa FL, Miranda-Saksena M, Rixon FJ, Vittone V, et al. Herpes simplex virus type 1 capsid protein VP26 interacts with dynein light chains RP3 and Tctex1 and plays a role in retrograde cellular transport. J Biol Chem 279: 28522-30 (2004).
39. Diefenbach RJ, Miranda-Saksena M, Douglas MW, Cunningham AL. Transport and egress of herpes simplex virus in neurons. Rev Med Virol 18: 35-51 (2008).
40. De Regge N, Nauwynck HJ, Greenen K, Krummenacher C, Cohen GH, Eisenberg RJ, et al. alpha-Herpesvirus glycoprotein D interaction with sensory neurons triggers formation of varicosities that serve as virus exit sites. J Cell Biol 174: 267-75 (2006).
41. Saksena MM, Wakisaka H, Tijono B, Boadle RA, Rixon F, Takahashi H, et al. Herpes simplex virus type 1 accumulation, envelopment and exit in growth cones, varicosities in mid distal regions of axons. J Virol 80: 3592-606 (2006).
42. Wang F, Tang W, McGraw H, Bennett J, Enquist L, Friedman HM. Herpes simplex virus type 1 Glycoprotein E is required for axonal localization of capsid, tegument and membrane glycoproteins. J Virol 79: 13362-72 (2005).
43. Wozniak MA, Mee AP, and Izthaki RF. Herpes simplex virus type 1 DNA is located within Alzheimer’s disease amyloid plaques. J Pathol 217(1): 131-8 (2009).
44. Carter CJ. Alzheimer’s disease plaques and tangles: Cemeteries of a pyrrhic victory of the immune defense network against herpes simplex infection at the expense of complement and inflammationmediated neuronal destruction. Neurochem Int 58(3): 301-20 (2011).
45. Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hyman B, et al. The Alzheimer’s disease-associated amyloid β-protein is an antimicrobial peptide. PLoS One 5(3): 9505-14 (2010).
46. Kammerman EM, Neumann DM, Ball MJ, Lukiw W, Hill JM. Senile plaques in Alzheimer’s diseased brains: Possible association of β-amyloid with herpes simplex virus type-1 (HSV-1) L particles. Med Hypotheses 66(2): 294-9 (2006).
47. Wozniak MA, Itzhaki RF, Shipley SJ, Dobson CB. Herpes simplex virus infection causes cellular β-amyloid accumulation and secretase upregulation. Neurosci Lett 429(2-3): 95-100 (2007).
48. De Chiara G, Marcocci ME, Civitelli L, Argnani R, Grassi C, Palamara AT. APP processing induced by herpes simplex virus type 1 (HSV-1) yields several APP fragments in human and rat neuronal cells. PLoS One 5: 13989-14002 (2010).
49. Maloney MT, Minamide LS, Kinley AW, Boyle JA, Bamburg JR. β-secretase-cleaved amyloid precursor protein accumulates at actin inclusions induced in neurons by stress or Aβ: Feedforward mechanism for Alzheimer disease. J Neurosci 25: 11313-21 (2005).
50. Gotz J, Ittner LM, Kins S. Do axonal defects in tau and amyloid precursor protein transgenic animals model axonopothy in Alzheimer’s disease. J Neurochem 98: 993-1006 (2006).
51. Duka V, Lee JH, Credle J, Wills J, Oaks A, Smolinsky C, et al. Identification of the sites of Tau hyperphosphorylation and activation of Tau kinases in synucleinopathies and Alzheimer’s diseases. PLoS One 8(9): e75025 (2013).
52. Bandyopadhyay B, Li G, Yin H, Kuret J. Tau aggregation and toxicity in a cell culture model of tauopathy. J Biol Chem 282: 16454-64 (2007).
53. Gong CX, Grundke-Iqbal I, Iqbal K. Targeting tau protein in Alzheimer’s disease. Drugs Aging 27(5): 351-65 (2010).
54. Metcalfe MJ, Figueiredo-Pereira M.E. Relationship between tau pathology and neuroinflammation in Alzheimer’s disease. Mt Sinai J Med 77(1): 50-8 (2010).
55. Grundke-Iqbal I, Iqbal K, Tung YC, Quinlan M, Wisniewski HM, Binder LI. Abnormal phosphorylation of the microtubuleassociated protein tau in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci USA 83(13): 4913-7 (1986).
56. Stokin GB, Lillo C, Falzone TL, Brusch RG, Rockenstein E, Mount SL, et al. Axonopathy and transport deficits early in the pathogenesis of Alzheimer’s disease. Science 307(5713): 1282-8 (2005).
57. Hensley K, Floyd RA, Geddes J, Markesbery WR, Johnson GVW, Bing G. p38 kinase is activated in Alzheimer’s disease brain. J Neurochem 72: 2053-8 (1999).
58. Zhu XM, Rottkamp CA, Boux H, Takeda A, Perry G, Smith MA. Activation of p38 Kinase Links Tau Phosphorylation, Oxidative Stress, and Cell Cycle_Related Events in Alzheimer Disease. J Neuropathol Exp Neurol 59(10): 880-8 (2000).
59. Lafon M, Megret F, Lafage M, Prehaud C. The innate immune facet of brain: Human neurons express TLR-3 and sense viral infections. J Mol Neurosci 29(3): 185-94 (2006).
60. Salminen A, Ojala J, Kauppinen A, Kaarniranta K, Suuronen T. Inflammation in Alzheimer’s disease: Amyloid β oligomers trigger innate immunity defence via pattern recognition receptors. Prog Neurobiol 87(3): 181-94 (2009).
61. Wozniak MA, Frost AL, Itzhaki RF. Alzheimer’s disease specific tau phosphorylation is induced by Herpes Simplex Virus Type 1. J Alzheimers Dis 16(2): 341-50 (2009).
62. Hernandez F, Lucas JJ, Avila J. GSK3 and tau: Two convergance points in Alzheimer’s disease. J Alzheimers Dis 33: s141-4 (2013).
63. Bose A, Mouton-Liger F, Paquet C, Mazot P, Vigny M, Gray F, et al. Modulation of tau phosphorylation by the kinase PKR: Implications in Alzheimer’s disease. Brain Pathol 21(2): 189-200 (2011).
64. Bullido MJ, Martinez-Garcia A, Tenorio R, Sastre I, Muñoz DG, Frank A, et al. Double srtranded RNA activated EIF2α kinase (EIF2AK2, PKR) is associated with Alzheimer’s disease. Neurobiol Aging 29(8): 1160-6 (2008).
65. Préhaud C, Mégret F, Lafage M, Lafon M. Virus infection switches TLR-3 positive human neurons to become strong producers of beta interferon. J Virol 79(20): 12893-904 (2005).
66. Paquet C, Mouton-Liger F, Meurs EF, Mazot P, Bouras C, Pradier L, et al. The PKR activator PACT is induced by Aβ: Invovlement in Alzheimer’s Disease. Brain Pathol 22(2): 219-29 (2012).
67. Lerchundi R, Neira R, Valdivia S, Vio K, Concha MI, Zombrano A, et al. Tau cleavage at D421 by caspase 3 is induced in neurons and astrocytes infected with herpes simplex virus type 1. J Alzheimers Dis 23(3): 513-20 (2011).
68. Rissman RA, Poon WW, Blurton-Jones M, Oddo S, Torp R, Vitek MP, et al. Caspase cleavage of tau is an early event in Alzheimer disease tangle pathology. J Clin Invest 114(1): 121-30 (2004).
69. Kramer T, Enquist LW. Alphaherpesvirus infection disrupts mitochondrial transport in neurons. Cell Host Microbe 11(5): 504-14 (2012).
70. 2+-mediated APP phosphorylation and Aβ accumulation in rat cortical neurons. Neurobiol Aging 32(12): 13-26 (2011).
71. Saffran HA, Pare JM, Corcoran JA, Weller SK, Smiley JR. Herpes simplex virus eliminates host mitochondrial DNA. EMBO Rep 8(2): 188-93 (2007).
72. Rhein V, Song X, Wiesner A, Ittner LM, Baysang G, Meier F, et al. Amyloid-β and tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimer’s disease mice. Proc Natl Acad Sci USA 106: 20057-62 (2009).
73. Yang Y, Mufson EJ, Herrup K. Neuronal cell death is preceded by cell cycle events at all stages of Alzheimer’s disease. J Neurosci 23(7): 2557-63 (2003).
74. Schang LM. Cyclin dependent kinases as cellular targets for antiviral drugs. J Antimicrob Chemother 50(6): 779-92 (2002).
75. Kuny CV, Chinchilla K, Culbertson MR, Kalejta RF. Cyclindependent kinase-like function is shared by the beta-and gammasubset of the conserved herpesvirus protein kinases. PLoS Pathog 6(9): 1092-108 (2010).
76. Kim DB, DeLuca NA. Phosphorylation of transcription factor Sp1 during herpes simplex virus type 1 infection. J Virol 76: 6473-9 (2002).
77. Jacob T, Van den Broeke C, Favoreel HW. Viral serine/threonine protein kinases. J Virol 85: 1158-73 (2011).
78. Flemington EK. Herpesvirus lytic replication and the cell cycle: Arresting new developments. J Virol 75: 4475-81 (2001).
79. Jordan R, Schang L, Schaffer PA. Transactivation of herpes simplex virus type 1 immediate-early gene expression by virionassociated factors is blocked by an inhibitor of cyclin dependent protein kinases. J Virol 73: 8843-7 (1999).
80. Advani S, Weichselbaum RR, Roizman B. cdc2 Cyclin dependent kinase binds and phosphorylates Herpes simplex virus 1 UL42 DNA processivity factor. J Virol 75: 10326-33 (2001).
81. Rubio-Perez JM and Morillas-Ruiz JM. A review: Inflammatory processes in Alzheimer’s disease, role of cytokines. ScientificWorld J 756357: 1-15 (2012).
82. Aloisi F. Immune function of microglia. Glia 36(2): 165-79 (2001).
83. Liu L, Chan C. The role of the inflammasome in Alzheimer’s disease. Ageing Res Rev 15: 6-15 (2014).
84. Gandy S, Heppner FL. Microglia as dynamic and essential components of the amyloid hypothesis. Neuron 78(4): 575-7 (2013).
85. Landreth GE, Reed-Geaghan EG. TLRs in Alzheimer’s Disease. Curr Top Microbiol Immunol 336: 137-53 (2009).
86. Paludan SR, Bowie AG, KA Horan, Fitzgerald KA. Recognition of herpesviruses by the innate immune system. Nat Rev Immunol 11(2): 143-54 (2011).
87. Viejo-Borbolla A, Martinez-Martín N, Nel HJ, Rueda P, Blanco S, Arenzana-Seisdedos F, et al. Enhancement of chemokine function as an immunomodulatory strategy employed by human herpesviruses. PLoS Pathog 8(2): 1002497 (2012).
88. Maussang D, Vischer HF, Leurs R, Smit MJ. Herpesvirus-encoded G protein-coupled receptors as modulators of cellular function. Mol Pharmacol 76(4): 692-701 (2009).
89. Xia MQ, Bacskai BJ, Knowles RB, Qin SX, Hyman BT. Expression of the chemokine receptor CXCR3 on neurons and the elevated expression of its ligand IP-10 in reactive astrocytes: In vitro ERK1/2 activation and role in Alzheimer’s disease. J Neuroimmunol 108(1-2): 227-35 (2000).
90. Zhu Z, Castellani RJ, Takeda A, Nunomura A, Atwood CS, Perry G, et al. Differential activation of neuronal ERK, JNK/SAPK and p38 in Alzheimer disease: The ‘two hit’ hypothesis. Mech Ageing Dev 123(1): 39-46 (2001).
91. Hargett D, McLean T, and Bachenheimer SL. Herpes simplex virus ICP27 activation of stress kinases JNK and p38. J Virol 79(13): 8348-60 (2005).
92. McLean TI, Bachenheimer SL. Activation of cJUN N-terminal kinase by herpes simplex virus type 1 enhances viral replication. J Virol 73(10): 8415-26 (1999).
93. Lokensgard JR, Hu S, Sheng W, Van Oijen M, Cox D, Cheeran MC, et al. Robust expression of TNF-α, IL-1β, RANTES, and IP-10 by human microglial cells during nonproductive infection with herps simplex virus. J Neurovirol 7(3): 208-19 (2001).
94. Gouras GK, Tampellini D, Takahashi R, Capetillo-Zerate E. Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease. Acta Neuropathol 119(5): 523-41 (2010).
95. Salminen A, Kaarniranta K, Kauppinen A, Ojala J, Haapasalo A, Soininen H, et al. Impaired autophagy and APP processing in Alzheimer’s disease: The potential role of Beclin 1 interactome. Prog Neurobiol 106-107: 33-54 (2013).
96. Nixon RA, Wegiel J, Kumar A, Yu WH, Peterhoff C, Cataldo A, et al. Extensive involvement of autophagy in Alzheimer disease: An immuno-electron microscopy study. J Neuropathol Exp Neurol 64(2): 113-22 (2005).
97. Szpara ML, Kobiler O, Enquist LW. A common neuronal response to alphaherpesvirus infection. J Neuroimmune Pharmacol 5(3): 418-27 (2010).
98. Itzhaki RF, Cosby SL, Wozniak MA. Herpes simplex virus type 1 and Alzheimer’s disease: The autophagy connection. J Neurovirol 14(1): 1-4 (2008).
99. Orvedahl A, Levine B. Autophagy and viral neurovirulence. Cell Microbiol 10(9): 1747-56 (2008).
100. Yordy B, Iijima N, Huttner A, Leib D, Iwasaki A. A neuron specific role for autophagy in antiviral defnese against herpes simplex virus. Cell Host Microbe 12(3): 334-45 (2012).
101. Orvedahl A, Alexander D, Tallóczy Z,. HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein. Cell Host Microbe 1(1): 23-35 (2007).
102. Jaeger PA, Wyss-Coray T. Beclin 1 complex in autophagy and Alzheimer disease. Arch Neurol 67(10): 1181-4 (2010).
103. Letenneur L, Pérès K, Fleury H, Garrigue I, Barberger-Gateau P, Helmer C, et al. Seropositivity to Herpes Simplex antibodies and the risk of Alzheimer’s disease: A population based cohort study. PLoS One 3(11): 0003637 (2008).
104. Itzhaki RF. Herpes simplex virus type 1 and Alzheimer’s disease: Increasing evidence for a major role of the virus. Front Aging Neurosci 6: 202 (2014).
105. Cattaneo A, Calissano P. Nerve growth factor and Alzheimer’s disease: New facts for an old hypothesis. Mol Neurobiol 46(3): 588-604 (2012).
106. Villa A, Latasa MJ, Pascual A. Nerve growth factor modulates the expression and secretion of β-amyloid precursor protein through different mechanisms in PC12 cells. J Neurochem 77(4): 1077-84 (2001).
107. Lahiri DK, Maloney B. The "LEARn" Latent Early-life Associated Regulation) model integrates environmental risk factors and the developmental basis of Alzheimer’s Disease and proposes remedial steps. Exp Gerontol 45: 291-296 (2010).
108. Wang QY, Zhou C, Hophnson KE, Colgrove RC, Coen DM Knipe DM. Herpesviral latency-associated transcript gene promotes assembly of heterochromatin on viral lytic-gene promoters in latent infection. Proc Natl Acad Sci USA 102(44): 16055-16059 (2005).
109. Lahiri D, Maloney B, Zawia N. The LEARn model: An epigenetic explanation for idiopathic neurobiological diseases. Mol Psychiatry 14: 002-1008 (2009).
110. Spinney L. Alzheimer’s disease: The forgetting gene. Nature 510: 26-28 (2014).
111. Itzhaki R, Lin W. Herpes simplex virus type I in brain and the type 4 allele of apolipoprotein E gene are a combined risk factor for Alzheimer’s Disease. Biochem Soc Transact 26(2): 27-277 (1998).
112. Burgos JS, Ramirez C, Sastre I, Valdivieso F. Apolipoprotein E genotype influences vertical transmission of herpes simplex virus type I in a gender specific manner. Aging Cell 6: 841-2 (2007).
113. Olsen I, Singhrao SK. Can oral infection be a risk factor for Alzheimer’s disease?. J Oral Microbiol 7: 29143 (2015).