The molecular basis of herpes simplex virus latency

FEMS Microbiology Reviews

Volumn 36, Issue 3, 2012, Pages 684-705

  Nicoll, Michael P ^a   Proença, João T ^a   Efstathiou, Stacey ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

Chromatin; Epigenetics; Herpesvirus; MiRNA; Neurotropism; Pathogenesis; Reactivation

Indexed keywords

CASPASE 3; CYCLIC AMP; DOUBLE STRANDED DNA; GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; HISTONE; HOST CELL FACTOR C1; INTERFERON; MESSENGER RNA; MICRORNA; OCTAMER TRANSCRIPTION FACTOR 1; PHOSPHATIDYLINOSITOL 3 KINASE; POLY(ADENOSINE DIPHOSPHATE RIBOSE); PROTEIN KINASE C; PROTEIN VP16; VIRUS DNA; VIRUS PROTEIN;

ADAPTIVE IMMUNITY; ANTIBODY DETECTION; BACULOVIRUS; CD8+ T LYMPHOCYTE; CELL SURVIVAL; CHROMATIN; CYTOPLASM; DNA REPAIR; DNA REPLICATION; EPIGENETICS; EPITHELIUM CELL; GANGLION; GENE CONTROL; GENE EXPRESSION; GENE SILENCING; HERPES SIMPLEX; HERPES SIMPLEX VIRUS 1; HERPES SIMPLEX VIRUS 2; HUMAN; HYPERTHERMIA; IMMUNE EVASION; IN SITU HYBRIDIZATION; LATENT VIRUS INFECTION; MAJOR HISTOCOMPATIBILITY COMPLEX; MOLECULAR DIAGNOSIS; NICK END LABELING; NONHUMAN; PATHOGENESIS; PROGENY; PROTEIN LOCALIZATION; RABBIT; RECURRENT DISEASE; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; REVIEW; SENSORY NERVE CELL; TRANSCRIPTION REGULATION; VIRUS CELL INTERACTION; VIRUS DETECTION; VIRUS GENOME; VIRUS LATENCY; VIRUS MUTANT; VIRUS REPLICATION; VIRUS STRAIN; VIRUS SURVIVAL; VIRUS TRANSCRIPTION; VIRUS VIRULENCE;

GENE EXPRESSION REGULATION, VIRAL; HERPESVIRUS 1, HUMAN; HOST-PATHOGEN INTERACTIONS; HUMANS; NEURONS; TRANSCRIPTION, GENETIC; VIRUS ACTIVATION; VIRUS LATENCY;

HERPESVIRIDAE; HUMAN HERPESVIRUS 1; SIMPLEXVIRUS;

EID: 84859427551     PISSN: 01686445     EISSN: 15746976     Source Type: Journal    
DOI: 10.1111/j.1574-6976.2011.00320.x     Document Type: Review

References (208)

1. Ahmed M, Lock M, Miller CG & Fraser NW (2002) Regions of the herpes simplex virus type 1 latency-associated transcript that protect cells from apoptosis in vitro and protect neuronal cells in vivo. J Virol 76: 717-729.
2. Amelio AL, Giordani NV, Kubat NJ, O'neil JE & Bloom DC (2006) Deacetylation of the herpes simplex virus type 1 latency-associated transcript (LAT) enhancer and a decrease in LAT abundance precede an increase in ICP0 transcriptional permissiveness at early times postexplant. J Virol 80: 2063-2068.
3. Arthur J, Efstathiou S & Simmons A (1993) Intranuclear foci containing low abundance herpes simplex virus latency-associated transcripts visualized by non-isotopic in situ hybridization. J Gen Virol 74(Pt 7): 1363-1370.
4. Arthur JL, Scarpini CG, Connor V, Lachmann RH, Tolkovsky AM & Efstathiou S (2001) Herpes simplex virus type 1 promoter activity during latency establishment, maintenance, and reactivation in primary dorsal root neurons in vitro. J Virol 75: 3885-3895.
5. Bertke AS, Swanson SM, Chen J, Imai Y, Kinchington PR & Margolis TP (2011) A5-positive primary sensory neurons are nonpermissive for productive infection with herpes simplex virus 1 in vitro. J Virol 85: 6669-6677.
6. Bloom DC, Giordani NV & Kwiatkowski DL (2010) Epigenetic regulation of latent HSV-1 gene expression. Biochim Biophys Acta 1799: 246-256.
7. Boehmer PE & Nimonkar AV (2003) Herpes virus replication. IUBMB Life 55: 13-22.
8. Boissiere SL, Hughes T & O'Hare P (1999) HCF-dependent nuclear import of VP16. EMBO J 18: 480-489.
9. Boss IW, Plaisance KB & Renne R (2009) Role of virus-encoded microRNAs in herpesvirus biology. Trends Microbiol 17: 544-553.
10. Boutell C, Sadis S & Everett RD (2002) Herpes simplex virus type 1 immediate-early protein ICP0 and is isolated RING finger domain act as ubiquitin E3 ligases in vitro. J Virol 76: 841-850.
11. Branco FJ & Fraser NW (2005) Herpes simplex virus type 1 latency-associated transcript expression protects trigeminal ganglion neurons from apoptosis. J Virol 79: 9019-9025.
12. Burton EA, Hong C-S & Glorioso JC (2003) The stable 2.0-kilobase intron of the herpes simplex virus type 1 latency-associated transcript does not function as an antisense repressor of ICP0 in nonneuronal cells. J Virol 77: 3516-3530.
13. Cai W & Schaffer PA (1992) Herpes simplex virus type 1 ICP0 regulates expression of immediate-early, early, and late genes in productively infected cells. J Virol 66: 2904-2915.
14. Cai W, Astor TL, Liptak LM, Cho C, Coen DM & Schaffer PA (1993) The herpes simplex virus type 1 regulatory protein ICP0 enhances virus replication during acute infection and reactivation from latency. J Virol 67: 7501-7512.
15. Camarena V, Kobayashi M, Kim JY, Roehm P, Perez R, Gardner J, Wilson AC, Mohhr I & Chao MV (2010) Nature and duration of growth factor signaling through receptor tyrosine kinases regulates HSV-1 latency in neurons. Cell Host Microbe 8: 320-330.
16. Carpenter D, Hsiang C, Brown DJ, Jin L, Osorio N, BenMohamed L, Jones C & Wechsler SL (2007) Stable cell lines expressing high levels of the herpes simplex virus type 1 LAT are refractory to caspase 3 activation and DNA laddering following cold shock induced apoptosis. Virology 369: 12-18.
17. Carter KL & Roizman B (1996) Alternatively spliced mRNAs predicted to yield frame-shift proteins and stable intron 1 RNAs of the herpes simplex virus 1 regulatory gene alpha 0 accumulate in the cytoplasm of infected cells. P Natl Acad Sci USA 93: 12535-12540.
18. Chen SH, Kramer MF, Schaffer PA & Coen DM (1997) A viral function represses accumulation of transcripts from productive-cycle genes in mouse ganglia latently infected with herpes simplex virus. J Virol 71: 5878-5884.
19. Chen XP, Mata M, Kelley M, Glorioso JC & Fink DJ (2002) The relationship of herpes simplex virus latency associated transcript expression to genome copy number: a quantitative study using laser capture microdissection. J Neurovirol 8: 204-210.
20. Chiocca EA, Choi BB, Cai WZ, DeLuca NA, Schaffer PA, DiFiglia M, Breakefield XO & Martuza RL (1990) Transfer and expression of the lacZ gene in rat brain neurons mediated by herpes simplex virus mutants. New Biol 2: 739-746.
21. Ciacci-Zanella J, Stone M, Henderson G & Jones C (1999) The latency-related gene of bovine herpesvirus 1 inhibits programmed cell death. J Virol 73: 9734-9740.
22. Cliffe AR, Garber DA & Knipe DM (2009) Transcription of the herpes simplex virus latency-associated transcript promotes the formation of facultative heterochromatin on lytic promoters. J Virol 83: 8182-8190.
23. Coleman HM, Connor V, Cheng ZS, Grey F, Preston CM & Efstathiou S (2008) Histone modifications associated with herpes simplex virus type 1 genomes during quiescence and following ICP0-mediated de-repression. J Gen Virol 89: 68-77.
24. 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.
25. Cuchet D, Sykes A, Nicolas A, Orr A, Murray I, Sirma H, Heeren J, Bartelt A & Everett RD (2011) PML isoforms I and II participate in PML-dependent restriction of HSV-1 replication. J Cell Sci 124: 280-291.
26. Cui C, Griffiths A, Li G, Silva LM, Kramer MF, Gaasterland T, Wang XJ & Coen DM (2006) Prediction and identification of herpes simplex virus 1-encoded microRNAs. J Virol 80: 5499-5508.
27. Danaher RJ, Jacob RJ & Miller CS (1999) Establishment of a quiescent herpes simplex virus type 1 infection in neurally-differentiated PC12 cells. J Neurovirol 5: 258-267.
28. Dasgupta G & Benmohamed L (2011) Of mice and not humans: how reliable are animal models for evaluation of herpes CD8(+)-T cell-epitopes-based immunotherapeutic vaccine candidates? Vaccine 29: 5824-5836.
29. Deatly AM, Spivack JG, Lavi E, O'Boyle DR & Fraser NW (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.
30. Decman V, Kinchington PR, Harvey SA & Hendricks RL (2005) Gamma interferon can block herpes simplex virus type 1 reactivation from latency, even in the presence of late gene expression. J Virol 79: 10339-10347.
31. Deshmane SL & Fraser NW (1989) During latency, herpes simplex virus type 1 DNA is associated with nucleosomes in a chromatin structure. J Virol 63: 943-947.
32. Devi-Rao GB, Goodart SA, Hecht LM, Rochford R, Rice MK & Wagner EK (1991) Relationship between polyadenylated and nonpolyadenylated herpes simplex virus type 1 latency-associated transcripts. J Virol 65: 2179-2190.
33. Dobson AT, Margolis TP, Sedarati F, Stevens JG & Feldman LT (1990) A latent, nonpathogenic HSV-1-derived vector stably expresses beta-galactosidase in mouse neurons. Neuron 5: 353-360.
34. Dressler GR, Rock DL & Fraser NW (1987) Latent herpes simplex virus type 1 DNA is not extensively methylated in vivo. J Gen Virol 68: 1761-1765.
35. Du T, Zhou G, Khan S, Gu H & Roizman B (2010) Disruption of HDAC/CoREST/REST repressor by dnREST reduces genome silencing and increases virulence of herpes simplex virus. P Natl Acad Sci USA 107: 15904-15909.
36. Ecob-Prince MS, Preston CM, Rixon FJ, Hassan K & Kennedy PG (1993) Neurons containing latency-associated transcripts are numerous and widespread in dorsal root ganglia following footpad inoculation of mice with herpes simplex virus type 1 mutant in1814. J Gen Virol 74(Pt 6): 985-994.
37. Efstathiou S & Preston CM (2005) Towards an understanding of the molecular basis of herpes simplex virus latency. Virus Res 111: 108-119.
38. Efstathiou S, Minson AC, Field HJ, Anderson JR & Wildy P (1986) Detection of herpes simplex virus-specific DNA sequences in latently infected mice and in humans. J Virol 57: 446-455.
39. Everett RD (1984) Trans activation of transcription by herpes virus products: requirement for two HSV-1 immediate-early polypeptides for maximum activity. EMBO J 3: 3135-3141.
40. Everett RD (2000) ICP0, a regulator of herpes simplex virus during lytic and latent infection. Bioessays 22: 761-770.
41. Everett RD (2010) Depletion of CoREST does not improve the replication of ICP0 null mutant herpes simplex virus type 1. J Virol 84: 3695-3698.
42. Everett RD, Cross A & Orr A (1993) A truncated form of herpes simplex virus type 1 immediate-early protein Vmw110 is expressed in a cell type dependent manner. Virology 197: 751-756.
43. Everett RD, Boutell C & Orr A (2004) Phenotype of a herpes simplex virus type 1 mutant that fails to express immediate-early regulatory protein ICP0. J Virol 78: 1763-1774.
44. Everett RD, Rechter S, Papior P, Tavalai N, Stamminger T & Orr A (2006) PML contributes to a cellular mechanism of repression of herpes simplex virus type 1 infection that is inactivated by ICP0. J Virol 80: 7995-8005.
45. Farrell MJ, Dobson AT & Feldman LT (1991) Herpes simplex virus latency-associated transcript is a stable intron. P Natl Acad Sci USA 88: 790-794.
46. Feldman LT, Ellison AR, Voytek CC, Yang L, Krause P & Margolis TP (2002) Spontaneous molecular reactivation of herpes simplex virus type 1 latency in mice. P Natl Acad Sci USA 99: 978-983.
47. Ferenczy MW, Ranayhossaini DJ & Deluca NA (2011) Activities of ICP0 involved in the reversal of silencing of quiescent herpes simplex virus 1. J Virol 85: 4993-5002.
48. Freeman ML, Sheridan BS, Bonneau RH & Hendricks RL (2007) Psychological stress compromises CD8+ T cell control of latent herpes simplex virus type 1 infections. J Immunol 179: 322-328.
49. Früh K, Ahn K, Djaballah H, Sempé P, van Endert PM, Tampé R, Peterson PA & Yang Y (1995) A viral inhibitor of peptide transporters for antigen presentation. Nature 375: 415-418.
50. Garber DA, Beverley SM & Coen DM (1993) Demonstration of circularization of herpes simplex virus DNA following infection using pulsed field gel electrophoresis. Virology 197: 459-462.
51. Garber DA, Schaffer PA & Knipe DM (1997) A LAT-associated function reduces productive-cycle gene expression during acute infection of murine sensory neurons with herpes simplex virus type 1. J Virol 71: 5885-5893.
52. Gebhardt BM & Halford WP (2005) Evidence that spontaneous reactivation of herpes virus does not occur in mice. Virol J 2: 67.
53. Giordani NV, Neumann DM, Kwiatkowski DL, Bhattacharjee PS, McAnany PK, Hill JM & Bloom DC (2008) During herpes simplex virus type 1 infection of rabbits, the ability to express the latency-associated transcript increases latent-phase transcription of lytic genes. J Virol 82: 6056-6060.
54. Gu H & Roizman B (2007) Herpes simplex virus-infected cell protein 0 blocks the silencing of viral DNA by dissociating histone deacetylases from the CoREST-REST complex. P Natl Acad Sci USA 104: 17134-17139.
55. Gu H & Roizman B (2009) The two functions of herpes simplex virus 1 ICP0, inhibition of silencing by the CoREST/REST/HDAC complex and degradation of PML, are executed in tandem. J Virol 83: 181-187.
56. Gu H, Liang Y, Mandel G & Roizman B (2005) Components of the REST/CoREST/histone deacetylase repressor complex are disrupted, modified, and translocated in HSV-1-infected cells. P Natl Acad Sci USA 102: 7571-7576.
57. Gussow AM, Giordani NV, Tran RK, Imai Y, Kwiatkowski DL, Rall GF, Margolis TP & Bloom DC (2006) Tissue-specific splicing of the herpes simplex virus type 1 latency-associated transcript (LAT) intron in LAT transgenic mice. J Virol 80: 9414-9423.
58. Hagglund R & Roizman B (2004) Role of ICP0 in the strategy of conquest of the host cell by herpes simplex virus 1. J Virol 78: 2169-2178.
59. Hagmann M, Georgiev O, Schaffner W & Douville P (1995) Transcription factors interacting with herpes simplex virus alpha gene promoters in sensory neurons. Nucleic Acids Res 23: 4978-4985.
60. Halford WP & Schaffer PA (2001) ICP0 is required for efficient reactivation of herpes simplex virus type 1 from neuronal latency. J Virol 75: 3240-3249.
61. Halford WP, Gebhardt BM & Carr DJ (1996) Mechanisms of herpes simplex virus type 1 reactivation. J Virol 70: 5051-5060.
62. Halford WP, Kemp CD, Isler JA, Davido DJ & Schaffer PA (2001) ICP0, ICP4, or VP16 expressed from adenovirus vectors induces reactivation of latent herpes simplex virus type 1 in primary cultures of latently infected trigeminal ganglion cells. J Virol 75: 6143-6153.
63. Hamza MA, Higgins DM, Feldman LT & Ruyechan WT (2007) The latency-associated transcript of herpes simplex virus type 1 promotes survival and stimulates axonal regeneration in sympathetic and trigeminal neurons. J Neurovirol 13: 56-66.
64. Harris RA, Everett RD, Zhu XX, Silverstein S & Preston CM (1989) Herpes simplex virus type 1 immediate-early protein Vmw110 reactivates latent herpes simplex virus type 2 in an in vitro latency system. J Virol 63: 3513-3515.
65. Held K, Junker A, Dornmair K, Meinl E, Sinicina I, Brandt T, Theil D & Derfuss T (2011) Expression of herpes simplex virus 1-encoded microRNAs in human trigeminal ganglia and their relation to local T-cell infiltrates. J Virol 85: 9680-9685.
66. Henderson G, Perng GC, Nesburn AB, Wechsler SL & Jones C (2004) The latency-related gene encoded by bovine herpesvirus 1 can suppress caspase 3 and caspase 9 cleavage during productive infection. J Neurovirol 10: 64-70.
67. Henderson G, Jaber T, Carpenter D, Wechsler SL & Jones C (2009) Identification of herpes simplex virus type 1 proteins encoded within the first 1.5 kb of the latency-associated transcript. J Neurovirol 15: 439-448.
68. Herrera FJ & Triezenberg SJ (2004) VP16-dependent association of chromatin-modifying coactivators and underrepresentation of histones at immediate-early gene promoters during herpes simplex virus infection. J Virol 78: 9689-9696.
69. Hill TJ, Field HJ & Blyth WA (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.
70. Hill TJ, Harbour DA & Blyth WA (1980) Isolation of herpes simplex virus from the skin of clinically normal mice during latent infection. J Gen Virol 47: 205-207.
71. Hill A, Jugovic P, York I, Russ G, Bennink J, Yewdell J, Ploegh H & Johnson D (1995) Herpes simplex virus turns off the TAP to evade host immunity. Nature 375: 411-415.
72. Honess RW & Roizman B (1974) Regulation of herpesvirus macromolecular synthesis. I. Cascade regulation of the synthesis of three groups of viral proteins. J Virol 14: 8-19.
73. Hoshino Y, Pesnicak L, Straus SE & Cohen JI (2009) Impairment in reactivation of a latency associated transcript (LAT)-deficient HSV-2 is not solely dependent on the latent viral load or the number of CD8(+) T cells infiltrating the ganglia. Virology 387: 193-199.
74. Huang J, Kent JR, Placek B, Whelan KA, Hollow CM, Zeng PY, Fraser NW & Berger SL (2006) Trimethylation of histone H3 lysine 4 by Set1 in the lytic infection of human herpes simplex virus 1. J Virol 80: 5740-5746.
75. Hunsperger EA & Wilcox CL (2003a) Caspase-3-dependent reactivation of latent herpes simplex virus type 1 in sensory neuronal cultures. J Neurovirol 9: 390-398.
76. Hunsperger EA & Wilcox CL (2003b) Capsaicin-induced reactivation of latent herpes simplex virus type 1 in sensory neurons in culture. J Gen Virol 84: 1071-1078.
77. Imai Y, Apakupakul K, Krause PR, Halford WP & Margolis TP (2009) Investigation of the mechanism by which herpes simplex virus type 1 LAT sequences modulate preferential establishment of latent infection in mouse trigeminal ganglia. J Virol 83: 7873-7882.
78. 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.
79. Jaber T, Henderson G, Li S, Perng G-C, Carpenter D, Wechsler SL & Jones C (2009) Identification of a novel herpes simplex virus type 1 transcript and protein (AL3) expressed during latency. J Gen Virol 90: 2342-2352.
80. Javier RT, Stevens JG, Dissette VB & Wagner EK (1988) A herpes simplex virus transcript abundant in latently infected neurons is dispensable for establishment of the latent state. Virology 166: 254-257.
81. 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.
82. Jin L, Perng GC, Mott KR, Osorio N, Naito J, Brick DJ, Carpenter D, Jones C & Wechsler SL (2005) A herpes simplex virus type 1 mutant expressing a baculovirus inhibitor of apoptosis gene in place of latency-associated transcript has a wild-type reactivation phenotype in the mouse. J Virol 79: 12286-12295.
83. Jin L, Carpenter D, Moerdyk-Schauwecker M, Vanarsdall AL, Osorio N, Hsiang C, Jones C & Wechsler SL (2008) Cellular FLIP can substitute for the herpes simplex virus type 1 latency-associated transcript gene to support a wild-type virus reactivation phenotype in mice. J Neurovirol 14: 389-400.
84. Jurak I, Kramer MF, Mellor JC, van Lint AL, Roth FP, Knipe DM & Coen DM (2010) Numerous conserved and divergent microRNAs expressed by herpes simplex viruses 1 and 2. J Virol 84: 4659-4672.
85. Jurak I, Griffiths A & Coen DM (2011) Mammalian alphaherpesvirus miRNAs. Biochim Biophys Acta 1809: 641-653.
86. Katz JP, Bodin ET & Coen DM (1990) Quantitative polymerase chain reaction analysis of herpes simplex virus DNA in ganglia of mice infected with replication-incompetent mutants. J Virol 64: 4288-4295.
87. Kent JR, Zeng PY, Atanasiu D, Gardner J, Fraser NW & Berger SL (2004) During lytic infection herpes simplex virus type 1 is associated with histones bearing modifications that correlate with active transcription. J Virol 78: 10178-10186.
88. Khanna KM, Lepisto AJ, Decman V & Hendricks RL (2004) Immune control of herpes simplex virus during latency. Curr Opin Immunol 16: 463-469.
89. Knickelbein JE, Khanna KM, Yee MB, Baty CJ, Kinchington PR & Hendricks RL (2008) Noncytotoxic lytic granule-mediated CD8+ T cell inhibition of HSV-1 reactivation from neuronal latency. Science 322: 268-271.
90. Knipe DM & Cliffe A (2008) Chromatin control of herpes simplex virus lytic and latent infection. Nat Rev Microbiol 6: 211-221.
91. Koelle DM & Corey L (2008) Herpes simplex: insights on pathogenesis and possible vaccines. Annu Rev Med 59: 381-395.
92. Koelle DM & Wald A (2000) Herpes simplex virus: the importance of asymptomatic shedding. J Antimicrob Chemother 45(Suppl T3): 1-8.
93. Kolb G & Kristie TM (2008) Association of the cellular coactivator HCF-1 with the Golgi apparatus in sensory neurons. J Virol 82: 9555-9563.
94. Kramer MF, Chen SH, Knipe DM & Coen DM (1998) Accumulation of viral transcripts and DNA during establishment of latency by herpes simplex virus. J Virol 72: 1177-1185.
95. Kramer MF, Jurak I, Pesola JM, Boissel S, Knipe DM & Coen DM (2011) Herpes simplex virus 1 microRNAs expressed abundantly during latent infection are not essential for latency in mouse trigeminal ganglia. Virology 417: 239-247.
96. Kristie TM (2007) Early events pre-initiation of alphaherpes viral gene expression. Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis (Arvin A, Campadelli-Fiume G, Mocarski E, Moore PS, Roizman B, Whitley R & Yamanishi K, eds). Cambridge University Press, Cambridge.
97. Kristie TM & Roizman B (1988) Differentiation and DNA contact points of host proteins binding at the cis site for virion-mediated induction of alpha genes of herpes simplex virus 1. J Virol 62: 1145-1157.
98. Kristie TM, Vogel JL & Sears AE (1999) Nuclear localization of the C1 factor (host cell factor) in sensory neurons correlates with reactivation of herpes simplex virus from latency. P Natl Acad Sci USA 96: 1229-1233.
99. Krummenacher C, Zabolotny JM & Fraser NW (1997) Selection of a nonconsensus branch point is influenced by an RNA stem-loop structure and is important to confer stability to the herpes simplex virus 2-kilobase latency-associated transcript. J Virol 71: 5849-5860.
100. Kubat NJ, Amelio AL, Giordani NV & Bloom DC (2004a) The herpes simplex virus type 1 latency-associated transcript (LAT) enhancer/rcr is hyperacetylated during latency independently of LAT transcription. J Virol 78: 12508-12518.
101. Kubat NJ, Tran RK, McAnany P & Bloom DC (2004b) Specific histone tail modification and not DNA methylation is a determinant of herpes simplex virus type 1 latent gene expression. J Virol 78: 1139-1149.
102. Kutluay SB & Triezenberg SJ (2009) Role of chromatin during herpesvirus infections. Biochim Biophys Acta 1790: 456-466.
103. Kwiatkowski DL, Thompson HW & Bloom DC (2009) The polycomb group protein Bmi1 binds to the herpes simplex virus 1 latent genome and maintains repressive histone marks during latency. J Virol 83: 8173-8181.
104. Kwon BS, Gangarosa LP, Burch KD, deBack J & Hill JM (1981) Induction of ocular herpes simplex virus shedding by iontophoresis of epinephrine into rabbit cornea. Invest Ophthalmol Vis Sci 21: 442-449.
105. Lacasse JJ & Schang LM (2010) During lytic infections, herpes simplex virus type 1 DNA is in complexes with the properties of unstable nucleosomes. J Virol 84: 1920-1933.
106. Lachmann RH, Sadarangani M, Atkinson HR & Efstathiou S (1999) An analysis of herpes simplex virus gene expression during latency establishment and reactivation. J Gen Virol 80(Pt 5): 1271-1282.
107. Lakin ND, Palmer R, Lillycrop KA, Howard MK, Burke LC, Thomas NS & Latchman DS (1995) Down regulation of the octamer binding protein Oct-1 during growth arrest and differentiation of a neuronal cell line. Brain Res Mol Brain Res 28: 47-54.
108. Latchman DS (1999) Regulation of DNA virus transcription by cellular POU family transcription factors. Rev Med Virol 9: 31-38.
109. Lee MG, Wynder C, Cooch N & Shiekhattar R (2005) An essential role for CoREST in nucleosomal histone 3 lysine 4 demethylation. Nature 437: 432-435.
110. Leib DA, Bogard CL, Kosz-Vnenchak M, Hicks KA, Coen DM, Knipe DM & Schaffer PA (1989) A deletion mutant of the latency-associated transcript of herpes simplex virus type 1 reactivates from the latent state with reduced frequency. J Virol 63: 2893-2900.
111. Leopardi R, Van Sant C & Roizman B (1997) The herpes simplex virus 1 protein kinase US3 is required for protection from apoptosis induced by the virus. P Natl Acad Sci USA 94: 7891-7896.
112. Liang Y, Vogel JL, Narayanan A, Peng H & Kristie TM (2009) Inhibition of the histone demethylase LSD1 blocks alpha-herpesvirus lytic replication and reactivation from latency. Nat Med 15: 1312-1317.
113. Lillycrop KA, Dent CL, Wheatley SC, Beech MN, Ninkina NN, Wood JN & Latchman DS (1991) The octamer-binding protein Oct-2 represses HSV immediate-early genes in cell lines derived from latently infectable sensory neurons. Neuron 7: 381-390.
114. Liu T, Tang Q & Hendricks RL (1996) Inflammatory infiltration of the trigeminal ganglion after herpes simplex virus type 1 corneal infection. J Virol 70: 264-271.
115. Lomonte P, Thomas J, Texier P, Caron C, Khochbin S & Epstein AL (2004) Functional interaction between class II histone deacetylases and ICP0 of herpes simplex virus type 1. J Virol 78: 6744-6757.
116. Mador N, Goldenberg D, Cohen O, Panet A & Steiner I (1998) Herpes simplex virus type 1 latency-associated transcripts suppress viral replication and reduce immediate-early gene mRNA levels in a neuronal cell line. J Virol 72: 5067-5075.
117. Maggioncalda J, Mehta A, Su YH, Fraser NW & Block TM (1996) Correlation between herpes simplex virus type 1 rate of reactivation from latent infection and the number of infected neurons in trigeminal ganglia. Virology 225: 72-81.
118. Margolis TP, Dawson CR & LaVail JH (1992) Herpes simplex viral infection of the mouse trigeminal ganglion. Immunohistochemical analysis of cell populations. Invest Ophthalmol Vis Sci 33: 259-267.
119. Margolis TP, Imai Y, Yang L, Vallas V & Krause PR (2007) Herpes simplex virus type 2 (HSV-2) establishes latent infection in a different population of ganglionic neurons than HSV-1: role of latency-associated transcripts. J Virol 81: 1872-1878.
120. Mark KE, Wald A, Magaret AS, Selke S, Olin L, Huang ML & Corey L (2008) Rapidly cleared episodes of herpes simplex virus reactivation in immunocompetent adults. J Infect Dis 198: 1141-1149.
121. Marshall KR, Lachmann RH, Efstathiou S, Rinaldi A & Preston CM (2000) Long-term transgene expression in mice infected with a herpes simplex virus type 1 mutant severely impaired for immediate-early gene expression. J Virol 74: 956-964.
122. McGeoch DJ, Rixon FJ & Davison AJ (2006) Topics in herpesvirus genomics and evolution. Virus Res 117: 90-104.
123. McMahon R & Walsh D (2008) Efficient quiescent infection of normal human diploid fibroblasts with wild-type herpes simplex virus type 1. J Virol 82: 10218-10230.
124. Mehta A, Maggioncalda J, Bagasra O, Thikkavarapu S, Saikumari P, Valyi-Nagy T, Fraser NW & Block TM (1995) In situ DNA PCR and RNA hybridization detection of herpes simplex virus sequences in trigeminal ganglia of latently infected mice. Virology 206: 633-640.
125. Miller CS, Danaher RJ & Jacob RJ (2006) ICP0 is not required for efficient stress-induced reactivation of herpes simplex virus type 1 from cultured quiescently infected neuronal cells. J Virol 80: 3360-3368.
126. Moriya A, Yoshiki A, Kita M, Fushiki S & Imanishi J (1994) Heat shock-induced reactivation of herpes simplex virus type 1 in latently infected mouse trigeminal ganglion cells in dissociated culture. Arch Virol 135: 419-425.
127. Muylaert I, Tang KW & Elias P (2011) Replication and recombination of herpes simplex virus DNA. J Biol Chem 286: 15619-15624.
128. Nevels M, Nitzsche A & Paulus C (2011) How to control an infectious bead string: nucleosome-based regulation and targeting of herpesvirus chromatin. Rev Med Virol 21: 154-180.
129. O'Hare P (1993) The virion transactivator of herpes simplex virus. Semin Virol 4: 145-155.
130. O'Hare P & Hayward GS (1985) Three trans-acting regulatory proteins of herpes simplex virus modulate immediate-early gene expression in a pathway involving positive and negative feedback regulation. J Virol 56: 723-733.
131. O'Neil JE, Loutsch JM, Aguilar JS, Hill JM, Wagner EK & Bloom DC (2004) Wide variations in herpes simplex virus type 1 inoculum dose and latency-associated transcript expression phenotype do not alter the establishment of latency in the rabbit eye model. J Virol 78: 5038-5044.
132. Orr MT, Mathis MA, Lagunoff M, Sacks JA & Wilson CB (2007) CD8 T cell control of HSV reactivation from latency is abrogated by viral inhibition of MHC class I. Cell Host Microbe 2: 172-180.
133. Pebody RG, Andrews N, Brown D et al. (2004) The seroepidemiology of herpes simplex virus type 1 and 2 in Europe. Sex Transm Infect 80: 185-191.
134. Peng W, Vitvitskaia O, Carpenter D, Wechsler SL & Jones C (2008) Identification of two small RNAs within the first 1.5-kb of the herpes simplex virus type 1-encoded latency-associated transcript. J Neurovirol 14: 41-52.
135. Perkins D, Pereira EFR, Gober M, Yarowsky PJ & Aurelian L (2002) The herpes simplex virus type 2 R1 protein kinase (ICP10 PK) blocks apoptosis in hippocampal neurons, involving activation of the MEK/MAPK survival pathway. J Virol 76: 1435-1449.
136. Perng GC, Ghiasi H, Slanina SM, Nesburn AB & Wechsler SL (1996) The spontaneous reactivation function of the herpes simplex virus type 1 LAT gene resides completely within the first 1.5 kilobases of the 8.3-kilobase primary transcript. J Virol 70: 976-984.
137. Perng GC, Jones C, Ciacci-Zanella J et al. (2000) Virus-induced neuronal apoptosis blocked by the herpes simplex virus latency-associated transcript. Science 287: 1500-1503.
138. Perng GC, Slanina SM, Ghiasi H, Nesburn AB & Wechsler SL (2001) The effect of latency-associated transcript on the herpes simplex virus type 1 latency-reactivation phenotype is mouse strain-dependent. J Gen Virol 82: 1117-1122.
139. Perng GC, Maguen B, Jin L et al. (2002) A gene capable of blocking apoptosis can substitute for the herpes simplex virus type 1 latency-associated transcript gene and restore wild-type reactivation levels. J Virol 76: 1224-1235.
140. Preston CM (2000) Repression of viral transcription during herpes simplex virus latency. J Gen Virol 81: 1-19.
141. Preston CM, Mabbs R & Nicholl MJ (1997) Construction and characterization of herpes simplex virus type 1 mutants with conditional defects in immediate early gene expression. Virology 229: 228-239.
142. Proença JT, Coleman HM, Connor V, Winton DJ & Efstathiou S (2008) A historical analysis of herpes simplex virus promoter activation in vivo reveals distinct populations of latently infected neurones. J Gen Virol 89: 2965-2974.
143. Proença JT, Coleman HM, Nicoll MP, Connor V, Preston CM, Arthur J & Efstathiou S (2011) An investigation of HSV promoter activity compatible with latency establishment reveals VP16 independent activation of HSV immediate early promoters in sensory neurones. J Gen Virol 92: 2575-2585.
144. Ramachandran S, Davoli KA, Yee MB, Hendricks RL & Kinchington PR (2010) Delaying the expression of herpes simplex virus type 1 glycoprotein B (gB) to a true late gene alters neurovirulence and inhibits the gB-CD8+ T-cell response in the trigeminal ganglion. J Virol 84: 8811-8820.
145. Rock DL & Fraser NW (1983) Detection of HSV-1 genome in central nervous system of latently infected mice. Nature 302: 523-525.
146. Rock DL, Nesburn AB, Ghiasi H, Ong J, Lewis TL, Lokensgard JR & Wechsler SL (1987) Detection of latency-related viral RNAs in trigeminal ganglia of rabbits latently infected with herpes simplex virus type 1. J Virol 61: 3820-3826.
147. Rødahl E & Haarr L (1997) Analysis of the 2-kilobase latency-associated transcript expressed in PC12 cells productively infected with herpes simplex virus type 1: evidence for a stable, nonlinear structure. J Virol 71: 1703-1707.
148. Roizman B (2011) The checkpoints of viral gene expression in productive and latent infection: the role of the HDAC/CoREST/LSD1/REST repressor complex. J Virol 85: 7474-7482.
149. Roizman B, Knipe D & Whitley R (2007) Herpes simplex viruses. Fields Virology (Knipe D, Howley P, Griffin DE, Lamb RA, Martin MA, Roizman B & Straus SE, eds), pp. 2501-2601. Lippincott Williams and Wilkins, New York.
150. Samaniego LA, Neiderhiser L & DeLuca NA (1998) Persistence and expression of the herpes simplex virus genome in the absence of immediate-early proteins. J Virol 72: 3307-3320.
151. Sawtell NM (1997) Comprehensive quantification of herpes simplex virus latency at the single-cell level. J Virol 71: 5423-5431.
152. Sawtell NM & Thompson RL (1992) Rapid in vivo reactivation of herpes simplex virus in latently infected murine ganglionic neurons after transient hyperthermia. J Virol 66: 2150-2156.
153. Sawtell NM, Poon DK, Tansky CS & Thompson RL (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.
154. Schiffer JT & Corey L (2009) New concepts in understanding genital herpes. Curr Infect Dis Rep 11: 457-464.
155. Sedarati F, Izumi KM, Wagner EK & Stevens JG (1989) Herpes simplex virus type 1 latency-associated transcription plays no role in establishment or maintenance of a latent infection in murine sensory neurons. J Virol 63: 4455-4458.
156. Sedarati F, Margolis TP & Stevens JG (1993) Latent infection can be established with drastically restricted transcription and replication of the HSV-1 genome. Virology 192: 687-691.
157. Shen W, Sa e Silva M, Jaber T, Vitvitskaia O, Li S, Henderson G & Jones C (2009) Two small RNAs encoded within the first 1.5 kilobases of the herpes simplex virus type 1 latency-associated transcript can inhibit productive infection and cooperate to inhibit apoptosis. J Virol 83: 9131-9139.
158. Shi YJ, Matson C, Lan F, Iwase S, Baba T & Shi Y (2005) Regulation of LSD1 histone demethylase activity by its associated factors. Mol Cell 19: 857-864.
159. Simmons A & Tscharke DC (1992) Anti-CD8 impairs clearance of herpes simplex virus from the nervous system: implications for the fate of virally infected neurons. J Exp Med 175: 1337-1344.
160. Slobedman B, Efstathiou S & Simmons A (1994) Quantitative analysis of herpes simplex virus DNA and transcriptional activity in ganglia of mice latently infected with wild-type and thymidine kinase-deficient viral strains. J Gen Virol 75(Pt 9): 2469-2474.
161. Smith RL, Pizer LI, Johnson EM & Wilcox CL (1992) Activation of second-messenger pathways reactivates latent herpes simplex virus in neuronal cultures. Virology 188: 311-318.
162. Smith RW, Malik P & Clements JB (2005) The herpes simplex virus ICP27 protein: a multifunctional post-transcriptional regulator of gene expression. Biochem Soc Trans 33: 499-501.
163. Speck PG & Simmons A (1992) Synchronous appearance of antigen-positive and latently infected neurons in spinal ganglia of mice infected with a virulent strain of herpes simplex virus. J Gen Virol 73(Pt 5): 1281-1285.
164. Steiner I, Spivack JG, Lirette RP, Brown SM, MacLean AR, Subak-Sharpe JH & Fraser NW (1989) Herpes simplex virus type 1 latency-associated transcripts are evidently not essential for latent infection. EMBO J 8: 505-511.
165. Steiner I, Spivack JG, Deshmane SL, Ace CI, Preston CM & Fraser NW (1990) A herpes simplex virus type 1 mutant containing a nontransinducing Vmw65 protein establishes latent infection in vivo in the absence of viral replication and reactivates efficiently from explanted trigeminal ganglia. J Virol 64: 1630-1638.
166. Stevens JG, Wagner EK, Devi-Rao GB, Cook ML & Feldman LT (1987) RNA complementary to a herpesvirus alpha gene mRNA is prominent in latently infected neurons. Science 235: 1056-1059.
167. Stow EC & Stow ND (1989) Complementation of a herpes simplex virus type 1 Vmw110 deletion mutant by human cytomegalovirus. J Gen Virol 70(Pt 3): 695-704.
168. Strang BL & Stow ND (2005) Circularization of the herpes simplex virus type 1 genome upon lytic infection. J Virol 79: 12487-12494.
169. Tang S, Bertke AS, Patel A, Wang K, Cohen JI & Krause PR (2008) An acutely and latently expressed herpes simplex virus 2 viral microRNA inhibits expression of ICP34.5, a viral neurovirulence factor. P Nat Acad Sci USA 105: 10931-10936.
170. Tang S, Patel A & Krause PR (2009) Novel less-abundant viral microRNAs encoded by herpes simplex virus 2 latency-associated transcript and their roles in regulating ICP34.5 and ICP0 mRNAs. J Virol 83: 1433-1442.
171. Terry-Allison T, Smith CA & DeLuca NA (2007) Relaxed repression of herpes simplex virus type 1 genomes in Murine trigeminal neurons. J Virol 81: 12394-12405.
172. Theil D, Derfuss T, Paripovic I, Herberger S, Meinl E, Schueler O, Strupp M, Arbusow V & Brandt T (2003) Latent herpesvirus infection in human trigeminal ganglia causes chronic immune response. Am J Pathol 163: 2179-2184.
173. Thomas SK, Gough G, Latchman DS, R S & Coffin RS (1999) Herpes simplex virus latency-associated transcript encodes a protein which greatly enhances virus growth, can compensate for deficiencies in immediate-early gene expression, and is likely to function during reactivation from virus latency. J Virol 73: 6618-6625.
174. Thompson RL & Sawtell NM (1997) The herpes simplex virus type 1 latency-associated transcript gene regulates the establishment of latency. J Virol 71: 5432-5440.
175. Thompson RL & Sawtell NM (2000) Replication of herpes simplex virus type 1 within trigeminal ganglia is required for high frequency but not high viral genome copy number latency. J Virol 74: 965-974.
176. Thompson RL & Sawtell NM (2001) Herpes simplex virus type 1 latency-associated transcript gene promotes neuronal survival. J Virol 75: 6660-6675.
177. Thompson RL & Sawtell NM (2006) Evidence that the herpes simplex virus type 1 ICP0 protein does not initiate reactivation from latency in vivo. J Virol 80: 10919-10930.
178. Thompson RL & Sawtell NM (2010) Therapeutic implications of new insights into the critical role of VP16 in initiating the earliest stages of HSV reactivation from latency. Future Med Chem 2: 1099-1105.
179. Thompson RL, Preston CM & Sawtell NM (2009) De novo synthesis of VP16 coordinates the exit from HSV latency in vivo. PLoS Pathog 5: e1000352.
180. Tumbar T, Sudlow G & Belmont AS (1999) Large-scale chromatin unfolding and remodeling induced by VP16 acidic activation domain. J Cell Biol 145: 1341-1354.
181. Umbach JL & Cullen BR (2009) The role of RNAi and microRNAs in animal virus replication and antiviral immunity. Genes Dev 23: 1151-1164.
182. Umbach JL, Kramer MF, Jurak I, Karnowski HW, Coen DM & Cullen BR (2008) MicroRNAs expressed by herpes simplex virus 1 during latent infection regulate viral mRNAs. Nature 454: 780-783.
183. Umbach JL, Nagel MA, Cohrs RJ, Gilden DH & Cullen BR (2009) Analysis of human alphaherpesvirus microRNA expression in latently infected human trigeminal ganglia. J Virol 83: 10677-10683.
184. Umbach JL, Wang K, Tang S, Krause PR, Mont EK, Cohen JI & Cullen BR (2010) Identification of viral microRNAs expressed in human sacral ganglia latently infected with herpes simplex virus 2. J Virol 84: 1189-1192.
185. Valyi-Nagy T, Deshmane S, Dillner A & Fraser NW (1991) Induction of cellular transcription factors in trigeminal ganglia of mice by corneal scarification, herpes simplex virus type 1 infection, and explantation of trigeminal ganglia. J Virol 65: 4142-4152.
186. Van Sant C, Hagglund R, Lopez P & Roizman B (2001) The infected cell protein 0 of herpes simplex virus 1 dynamically interacts with proteasomes, binds and activates the cdc34 E2 ubiquitin-conjugating enzyme, and possesses in vitro E3 ubiquitin ligase activity. P Natl Acad Sci USA 98: 8815-8820.
187. Wagner EK & Bloom DC (1997) Experimental investigation of herpes simplex virus latency. Clin Microbiol Rev 10: 419-443.
188. Wakim LM, Jones CM, Gebhardt T, Preston CM & Carbone FR (2008) CD8(+) T-cell attenuation of cutaneous herpes simplex virus infection reduces the average viral copy number of the ensuing latent infection. Immunol Cell Biol 86: 666-675.
189. Wald A & Corey L (2007) Persistence in the population: epidemiology, transmission. Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis (Arvin A, Campadelli-Fiume G, Mocarski E, Moore PS, Roizman B, Whitley R & Yamanishi K, eds). Cambridge University Press, Cambridge.
190. Wald A, Zeh J, Selke S, Warren T, Ryncarz AJ, Ashley R, Krieger JN & Corey L (2000) Reactivation of genital herpes simplex virus type 2 infection in asymptomatic seropositive persons. N Engl J Med 342: 844-850.
191. Wang K, Lau TY, Morales M, Mont EK & Straus SE (2005a) Laser-capture microdissection: refining estimates of the quantity and distribution of latent herpes simplex virus 1 and varicella-zoster virus DNA in human trigeminal Ganglia at the single-cell level. J Virol 79: 14079-14087.
192. Wang QY, Zhou C, Johnson KE, Colgrove RC, Coen DM & Knipe DM (2005b) Herpesviral latency-associated transcript gene promotes assembly of heterochromatin on viral lytic-gene promoters in latent infection. P Natl Acad Sci USA 102: 16055-16059.
193. Weber PC & Wigdahl B (1992) Identification of dominant-negative mutants of the herpes simplex virus type 1 immediate-early protein ICP0. J Virol 66: 2261-2267.
194. Weber PC, Kenny JJ & Wigdahl B (1992) Antiviral properties of a dominant negative mutant of the herpes simplex virus type 1 regulatory protein ICP0. J Gen Virol 73(Pt 11): 2955-2961.
195. Whitlow Z & Kristie TM (2009) Recruitment of the transcriptional coactivator HCF-1 to viral immediate-early promoters during initiation of reactivation from latency of herpes simplex virus type 1. J Virol 83: 9591-9595.
196. Wilcox CL & Johnson EM (1987) Nerve growth factor deprivation results in the reactivation of latent herpes simplex virus in vitro. J Virol 61: 2311-2315.
197. Wilcox CL & Johnson EM (1988) Characterization of nerve growth factor-dependent herpes simplex virus latency in neurons in vitro. J Virol 62: 393-399.
198. 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.
199. Wilcox CL, Smith RL, Everett RD & Mysofski D (1997) The herpes simplex virus type 1 immediate-early protein ICP0 is necessary for the efficient establishment of latent infection. J Virol 71: 6777-6785.
200. Wu TT, Su YH, Block TM & Taylor JM (1996) Evidence that two latency-associated transcripts of herpes simplex virus type 1 are nonlinear. J Virol 70: 5962-5967.
201. Wu TT, Su YH, Block TM & Taylor JM (1998) Atypical splicing of the latency-associated transcripts of herpes simplex type 1. Virology 243: 140-149.
202. Wysocka J & Herr W (2003) The herpes simplex virus VP16-induced complex: the makings of a regulatory switch. Trends Biochem Sci 28: 294-304.
203. Xu F, Schillinger JA, Sternberg MR, Johnson RE, Lee FK, Nahmias AJ & Markowitz LE (2002) Seroprevalence and coinfection with herpes simplex virus type 1 and type 2 in the United States, 1988-1994. J Infect Dis 185: 1019-1024.
204. Yang L, Voytek CC & Margolis TP (2000) Immunohistochemical analysis of primary sensory neurons latently infected with herpes simplex virus type 1. J Virol 74: 209-217.
205. Yeh L & Schaffer PA (1993) A novel class of transcripts expressed with late kinetics in the absence of ICP4 spans the junction between the long and short segments of the herpes simplex virus type 1 genome. J Virol 67: 7373-7382.
206. Zabolotny JM, Krummenacher C & Fraser NW (1997) The herpes simplex virus type 1 2.0-kilobase latency-associated transcript is a stable intron which branches at a guanosine. J Virol 71: 4199-4208.
207. Zhou G, Galvan V, Campadelli-Fiume G & Roizman B (2000) Glycoprotein D or J delivered in trans blocks apoptosis in SK-N-SH cells induced by a herpes simplex virus 1 mutant lacking intact genes expressing both glycoproteins. J Virol 74: 11782-11791.
208. Zwaagstra JC, Ghiasi H, Slanina SM, Nesburn AB, Wheatley SC, Lillycrop K, Wood J, Latchman DS, Patel K & Wechsler SL (1990) Activity of herpes simplex virus type 1 latency-associated transcript (LAT) promoter in neuron-derived cells: evidence for neuron specificity and for a large LAT transcript. J Virol 64: 5019-5028.