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Neurotropic Viral Infections pp 111–134Cite as

The Herpes Simplex Viruses

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Abstract

The Herpes Simplex Viruses (HSVs) are neurotropic viruses that establish lifelong latent infections in the peripheral nerve ganglia of humans. While these viruses most commonly result in asymptomatic infections, they are associated with a wide spectrum of clinical diseases ranging from cold sores and genital lesions to encephalitis and blindness. The latent virus that is present in the nerve ganglia reactivates periodically and is shed virus at the initial site of infection, often in the absence of clinical symptoms. There are currently antivirals that reduce the frequency and severity of the recurrences, but there is no vaccine or cure.

This chapter gives an overview of the biology, epidemiology, clinical diseases, and molecular biology of HSV. Model systems that are used to study the molecular basis of HSV latency and reactivation are discussed and recent insights into the regulation of HSV latency and reactivation through noncoding RNAs and chromatin are presented. Finally, we conclude with a summary of research on new therapies and prospects for a vaccine.

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References

  • Advani SJ, Mezhir JJ, Roizman B, Weichselbaum RR (2006) ReVOLT: radiation-enhanced viral oncolytic therapy. Int J Radiat Oncol Biol Phys 66(3):637–646

    Article  CAS  PubMed  Google Scholar 

  • Aghi M, Martuza RL (2005) Oncolytic viral therapies—the clinical experience. Oncogene 24(52):7802–7816

    Article  CAS  PubMed  Google Scholar 

  • 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 neural cells in vivo. J Virol 76(2):717–729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(4):2063–2068

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berman EJ, Hill JM (1985) Spontaneous ocular shedding of HSV-1 in latently infected rabbits. Invest Ophthalmol Vis Sci 26:587–590

    CAS  PubMed  Google Scholar 

  • 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(13):6669–6677. doi:10.1128/JVI.00204-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bloom DC (2004) HSV LAT and neuronal survival. Int Rev Immunol 23(1–2):187–198

    Article  CAS  PubMed  Google Scholar 

  • Bloom DC, Giordani NV, Kwiatkowski DL (2010) Epigenetic regulation of latent HSV-1 gene expression. Biochim Biophys Acta 1799(3–4):246–256. doi:10.1016/j.bbagrm.2009.12.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brandt CR (2005) The role of viral and host genes in corneal infection with herpes simplex virus type 1. Exp Eye Res 80(5):607–621

    Article  CAS  PubMed  Google Scholar 

  • Burke RL, Hartog K, Croen KD, Ostrove JM (1991) Detection and characterization of latent HSV RNA by in situ and northern blot hybridization in guinea pigs. Virology 181(2):793–797

    Article  CAS  PubMed  Google Scholar 

  • Camarena V, Kobayashi M, Kim JY, Roehm P, Perez R, Gardner J, Wilson AC, Mohr 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(4):320–330. doi:10.1016/j.chom.2010.09.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Campadelli-Fiume G, Menotti L, Avitabile E, Gianni T (2012) Viral and cellular contributions to herpes simplex virus entry into the cell. Curr Opin Virol 2(1):28–36. doi:10.1016/j.coviro.2011.12.001

    Article  CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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(16):8182–8190. doi:10.1128/JVI.00712-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cone RW, Hobson AC, Palmer J, Remington M, Corey L (1991) Extended duration of herpes simplex virus DNA in genital lesions detected by the polymerase chain reaction. J Infect Dis 164:757–760

    Article  CAS  PubMed  Google Scholar 

  • Cook ML, Bastone VB, Stevens JG (1974) Evidence that neurons harbor latent herpes simplex virus. Infect Immun 9(5):946–951

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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(11):5499–5508. doi:10.1128/JVI.00200-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deatly AM, Spivack JG, Lavi E, Fraser NW (1987) RNA from an immediate early region of the type 1 herpes simplex virus genome is present in the trigeminal ganglia of latently infected mice. Proc Natl Acad Sci U S A 84(10):3204–3208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deshmane SL, Fraser NW (1989) During latency, herpes simplex virus type 1 DNA is associated with nucleosomes in a chromatin structure. J Virol 63(2):943–947

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dobson AT, Sederati F, Devi RG, Flanagan WM, Farrell MJ, Stevens JG, Wagner EK, Feldman LT (1989) Identification of the latency-associated transcript promoter by expression of rabbit beta-globin mRNA in mouse sensory nerve ganglia latently infected with a recombinant herpes simplex virus. J Virol 63(9):3844–3851

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dolan A, Jamieson FE, Cunningham C, Barnett BC, McGeoch DJ (1998) The genome sequence of herpes simplex virus type 2. J Virol 72(3):2010–2021

    CAS  PubMed  PubMed Central  Google Scholar 

  • Douglas J, Schmidt O, Corey L (1983) Acquisition of neonatal HSV-1 infection from a paternal source contact. J Pediatr 103:908–910

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Eisenberg RJ, Atanasiu D, Cairns TM, Gallagher JR, Krummenacher C, Cohen GH (2012) Herpes virus fusion and entry: a story with many characters. Viruses 4(5):800–832. doi:10.3390/v4050800

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fenderson BA, Hahnel AC, Eddy EM (1983) Immunohistochemical localization of two monoclonal antibody-defined carbohydrate antigens during early murine embryogenesis. Dev Biol 100(2):318–327

    Article  CAS  PubMed  Google Scholar 

  • Flores O, Nakayama S, Whisnant AW, Javanbakht H, Cullen BR, Bloom DC (2013) Mutational inactivation of herpes simplex virus 1 microRNAs identifies viral mRNA targets and reveals phenotypic effects in culture. J Virol 87(12):6589–6603. doi:10.1128/JVI.00504-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Frampton AR Jr, Goins WF, Nakano K, Burton EA, Glorioso JC (2005) HSV trafficking and development of gene therapy vectors with applications in the nervous system. Gene Ther 12(11):891–901

    Article  CAS  PubMed  Google Scholar 

  • Gibson W, Roizman B (1971) Compartmentalization of spermine and spermidine in the herpes simplex virion. Proc Natl Acad Sci U S A 68(11):2818–2821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Giordani NV, Neumann DM, Kwiatkowski DL, Bhattacharjee PS, McAnany PK, Hill JM, Bloom DC (2008) During HSV-1 infection of rabbits, the ability to express the LAT increases latent-phase transcription of lytic genes. J Virol 82(12):6056–6060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goins WF, Sternberg LR, Croen KD, Krause PR, Hendricks RL, Fink DJ, Straus SE, Levine M, Glorioso JC (1994) A novel latency-active promoter is contained within the herpes simplex virus type 1 UL flanking repeats. J Virol 68(4):2239–2252

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gupta A, Gartner JJ, Sethupathy P, Hatzigeorgiou AG, Fraser NW (2006) Anti-apoptotic function of a microRNA encoded by the HSV-1 latency-associated transcript. Nature 442(7098):82–85

    CAS  PubMed  Google Scholar 

  • Hao S, Mata M, Glorioso JC, Fink DJ (2006) HSV-mediated expression of interleukin-4 in dorsal root ganglion neurons reduces neuropathic pain. Mol Pain 2:6

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hill J, Rayfield M, Haruta Y (1987) Strain specificity of spontaneous and adrenergically induced HSV-1 ocular reactivation in latently infected rabbits. Curr Eye Res 6(1):91–97

    Article  CAS  PubMed  Google Scholar 

  • Hill JM, Sedarati F, Javier RT, Wagner EK, Stevens JG (1990) Herpes simplex virus latent phase transcription facilitates in vivo reactivation. Virology 174(1):117–125

    Article  CAS  PubMed  Google Scholar 

  • Hill JM, Quenelle DC, Cardin RD, Vogel JL, Clement C, Bravo FJ, Foster TP, Bosch-Marce M, Raja P, Lee JS, Bernstein DI, Krause PR, Knipe DM, Kristie TM (2014) Inhibition of LSD1 reduces herpesvirus infection, shedding, and recurrence by promoting epigenetic suppression of viral genomes. Sci Transl Med 6(265):265ra169. doi:10.1126/scitranslmed.3010643

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ho DY, Mocarski ES (1989) Herpes simplex virus latent RNA (LAT) is not required for latent infection in the mouse. Proc Natl Acad Sci U S A 86(19):7596–7600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(8):3636–3646

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jaber T, Henderson G, Li S, Perng GC, 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(Pt 10):2342–2352. doi:10.1099/vir.0.013318-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jackson SA, DeLuca NA (2003) Relationship of herpes simplex virus genome configuration to productive and persistent infections. Proc Natl Acad Sci U S A 100(13):7871–7876

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jarman RG, Loutsch JM, Devi-Rao GB, Marquart ME, Banaszak MP, Zheng X, Hill JM, Wagner EK, Bloom DC (2002) The region of the HSV-1 latency-associated transcript required for epinephrine-induced reactivation in the rabbit does not include the 2.0 kb intron. Virology 292:59–69

    Article  CAS  PubMed  Google Scholar 

  • 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(1):254–257

    Article  CAS  PubMed  Google Scholar 

  • Jiang X, Brown D, Osorio N, Hsiang C, BenMohamed L, Wechsler SL (2015) Increased neurovirulence and reactivation of the herpes simplex virus type 1 latency-associated transcript (LAT)-negative mutant dLAT2903 with a disrupted LAT miR-H2. J Neurovirol 22(1):38–49. doi:10.1007/s13365-015-0362-y

    Article  PubMed  CAS  Google Scholar 

  • Jin L, Peng W, Perng GC, Brick DJ, Nesburn AB, Jones C, Wechsler SL (2003) Identification of herpes simplex virus type 1 latency-associated transcript sequences that both inhibit apoptosis and enhance the spontaneous reactivation phenotype. J Virol 77(11):6556–6561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(9):4659–4672. doi:10.1128/JVI.02725-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(18):10178–10186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim JY, Mandarino A, Chao MV, Mohr I, Wilson AC (2012) Transient reversal of episome silencing precedes VP16-dependent transcription during reactivation of latent HSV-1 in neurons. PLoS Pathog 8(2), e1002540. doi:10.1371/journal.ppat.1002540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Knipe DM, Cliffe A (2008) Chromatin control of herpes simplex virus lytic and latent infection. Nat Rev Microbiol 6(3):211–221

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi M, Kim JY, Camarena V, Roehm PC, Chao MV, Wilson AC, Mohr I (2012) A primary neuron culture system for the study of herpes simplex virus latency and reactivation. J Vis Exp (62). doi:10.3791/3823

  • 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(22):12508–12518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(3):1139–1149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(16):8173–8181. doi:10.1128/JVI.00686-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Lagunoff M, Roizman B (1994) Expression of a Herpes Simplex Virus 1 open reading frame antisense to the gamma 34.5 gene and transcribed by an RNA 3′ coterminal with the unspliced latency-associated transcript. J Virol 68(9):6021–6028

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lee LY, Schaffer PA (1998) A virus with a mutation in the ICP4-binding site in the L/ST promoter of herpes simplex virus type 1, but not a virus with a mutation in open reading frame P, exhibits cell-type-specific expression of gamma(1)34.5 transcripts and latency-associated transcripts. J Virol 72(5):4250–4264

    CAS  PubMed  PubMed Central  Google Scholar 

  • Leib DA, Bogard CL, Kosz VM, 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(7):2893–2900

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lepisto AJ, Frank GM, Hendricks RL (2007) How herpes simplex virus type 1 rescinds corneal privilege. Chem Immunol Allergy 92:203–212

    Article  CAS  PubMed  Google Scholar 

  • Liesegang TJ (1989) Epidemiology of ocular herpes simplex: natural history in Rochester, Minn 1950 through 1982. Arch Ophthalmol 107:1160–1165

    Article  CAS  PubMed  Google Scholar 

  • Maggioncalda J, Mehta A, Fraser NW, Block TM (1994) Analysis of a Herpes Simplex Virus type 1 LAT mutant with a deletion between the putative promoter and the 5′ end of the 2.0 kilobase transcript. J Virol 68(12):7816–7824

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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(4):1872–1878

    Article  CAS  PubMed  Google Scholar 

  • McGeoch DJ, Dalrymple MA, Davison AJ, Dolan A, Frame MC, McNab D, Perry LJ, Scott JE, Taylor P (1988) The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1. J Gen Virol 69(Pt 7):1531–1574

    Article  CAS  PubMed  Google Scholar 

  • McGeoch DJ, Cunningham C, McIntyre G, Dolan A (1991) Comparative sequence analysis of the long repeat regions and adjoining parts of the long unique regions in the genomes of herpes simplex viruses types 1 and 2. J Gen Virol 72(Pt 12):3057–3075

    Article  CAS  PubMed  Google Scholar 

  • Messer HG, Jacobs D, Dhummakupt A, Bloom DC (2015) Inhibition of H3K27me3-specific histone demethylases JMJD3 and UTX blocks reactivation of herpes simplex virus 1 in trigeminal ganglion neurons. J Virol 89(6):3417–3420. doi:10.1128/JVI.03052-14

    Article  CAS  PubMed  Google Scholar 

  • Miller CS, Berger JR, Mootoor Y, Avdiushko SA, Zhu H, Kryscio RJ (2006) High prevalence of multiple human herpesviruses in saliva from human immunodeficiency virus-infected persons in the era of highly active antiretroviral therapy. J Clin Microbiol 44(7):2409–2415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mitchell WJ, Deshmane SL, Dolan A, McGeoch DJ, Fraser NW (1990a) Characterization of herpes simplex virus type 2 transcription during latent infection of mouse trigeminal ganglia. J Virol 64(11):5342–5348

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mitchell WJ, Lirette RP, Fraser NW (1990b) Mapping of low abundance latency-associated RNA in the trigeminal ganglia of mice latently infected with herpes simplex virus type 1. J Gen Virol 71(Pt 1):125–132

    Article  CAS  PubMed  Google Scholar 

  • Naito J, Mukerjee R, Mott KR, Kang W, Osorio N, Fraser NW, Perng GC (2005) Identification of a protein encoded in the herpes simplex virus type 1 latency associated transcript promoter region. Virus Res 108(1–2):101–110. doi:10.1016/j.virusres.2004.08.011

    Article  CAS  PubMed  Google Scholar 

  • Nerurkar LS, West F, May M, Madden DL, Sever JL (1983) Survival of herpes simplex virus in water specimens collected from hot tubs in spa facilities and on plastic surfaces. JAMA 250(22):3081–3083

    Article  CAS  PubMed  Google Scholar 

  • Nesburn AB, Elliot JH, Leibowitz HM (1967) Spontaneous reactivation of experimental herpes simplex keratitis in rabbits. Arch Ophthalmol 78:523–529

    Article  CAS  PubMed  Google Scholar 

  • Neumann DM, Bhattacharjee PS, Giordani NV, Bloom DC, Hill JM (2007) In vivo changes in the patterns of chromatin structure associated with the latent herpes simplex virus type 1 genome in mouse trigeminal ganglia can be detected at early times after butyrate treatment. J Virol 81(23):13248–13253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nicosia M, Deshmane SL, Zabolotny JM, Valyi-Nagy T, Fraser NW (1993) Herpes simplex virus type 1 latency-associated transcript (LAT) promoter deletion mutants can express a 2-kilobase transcript mapping to the LAT region. J Virol 67(12):7276–7283

    CAS  PubMed  PubMed Central  Google Scholar 

  • Papanastassiou V, Rampling R, Fraser M, Petty R, Hadley D, Nicoll J, Harland J, Mabbs R, Brown M (2002) The potential for efficacy of the modified (ICP 34.5(−)) herpes simplex virus HSV1716 following intratumoural injection into human malignant glioma: a proof of principle study. Gene Ther 9(6):398–406

    Article  CAS  PubMed  Google Scholar 

  • 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(1):41–52. doi:10.1080/13550280701793957

    Article  CAS  PubMed  Google Scholar 

  • Perng G-C, Dunkel EC, Geary PA, Slanina SM, Ghiasi H, Kaiwar R, Nesburn AB, Wechsler SL (1994) The latency-associated transcript gene of herpes simplex virus type 1 (HSV-1) is required for efficient in vivo spontaneous reactivation of HSV-1 from latency. J Virol 68(12):8045–8055

    CAS  PubMed  PubMed Central  Google Scholar 

  • Perng GC, Jones C, Ciacci-Zanella J, Stone M, Henderson G, Yukht A, Slanina SM, Hofman FM, Ghiasi H, Nesburn AB, Wechsler SL (2000) Virus-induced neuronal apoptosis blocked by the herpes simplex virus latency-associated transcript. Science 287(5457):1500–1503

    Article  CAS  PubMed  Google Scholar 

  • Perng GC, Maguen B, Jin L, Mott KR, Kurylo J, BenMohamed L, Yukht A, Osorio N, Nesburn AB, Henderson G, Inman M, Jones C, Wechsler SL (2002) A novel herpes simplex virus type 1 transcript (AL-RNA) antisense to the 5′ end of the latency associated transcript produces a protein in infected rabbits. J Virol 76(16):8003–8010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perry LJ, McGeoch DJ (1988) The DNA sequences of the long repeat region and adjoining parts of the long unique region in the genome of herpes simplex virus type 1. J Gen Virol 69(Pt 11):2831–2846

    Article  CAS  PubMed  Google Scholar 

  • Pulkkanen KJ, Yla-Herttuala S (2005) Gene therapy for malignant glioma: current clinical status. Mol Ther 12(4):585–598

    Article  CAS  PubMed  Google Scholar 

  • Ribes JA, Steele AD, Seabolt JP, Baker DJ (2001) Six-year study of the incidence of herpes in genital and nongenital cultures in a central Kentucky medical center patient population. J Clin Microbiol 39(9):3321–3325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roberts C (2005) Genital herpes in young adults: changing sexual behaviours, epidemiology and management. Herpes 12(1):10–14

    PubMed  Google Scholar 

  • Roberts CM, Pfister JR, Spear SJ (2003) Increasing proportion of herpes simplex virus type 1 as a cause of genital herpes infection in college students. Sex Transm Dis 30(10):797–800

    Article  PubMed  Google Scholar 

  • Rock DL, Fraser NW (1985) Latent herpes simplex virus type 1 DNA contains two copies of the virion DNA joint region. J Virol 55(3):849–852

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rosato FE, Rosato EF, Plotkin SA (1970) Herpetic-paronychia—an occupational hazard of medical personnel. N Engl J Med 283:804

    Article  CAS  PubMed  Google Scholar 

  • 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(4):2150–2156

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sawtell NM, Triezenberg SJ, Thompson RL (2011) VP16 serine 375 is a critical determinant of herpes simplex virus exit from latency in vivo. J Neurovirol 17(6):546–551. doi:10.1007/s13365-011-0065-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(10):4455–4458

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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(2):687–691

    Article  CAS  PubMed  Google Scholar 

  • Sheridan PJ, Hermann EC (1971) Intraoral lesions of adults associated with herpes simplex virus. Oral Surg Oral Med Oral Pathol 32:390

    Article  CAS  PubMed  Google Scholar 

  • Smith JS, Robinson NJ (2002) Age-specific prevalence of infection with herpes simplex virus types 2 and 1: a global review. J Infect Dis 186(Suppl 1):S3–S28

    Article  PubMed  Google Scholar 

  • Stanberry LR (2004) Clinical trials of prophylactic and therapeutic herpes simplex virus vaccines. Herpes 11(Suppl 3):161A–169A

    PubMed  Google Scholar 

  • Stanberry LR, Kern ER, Richards JT, Abbott TM, Overall JC Jr (1982) Genital herpes in guinea pigs: pathogenesis of primary infection and description of recurrent disease. J Infect Dis 146:397–404

    Article  CAS  PubMed  Google Scholar 

  • Steiner I, Spivack JG, Lirette RP, Brown SM, MacLean AR, Subak SJH, Fraser NW (1989) Herpes simplex virus type 1 latency-associated transcripts are evidently not essential for latent infection. EMBO J 8(2):505–511

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stevens JG, Wagner EK, Devi RGB, Cook ML, Feldman LT (1987) RNA complementary to a herpesvirus alpha gene mRNA is prominent in latently infected neurons. Science 235(4792):1056–1059

    Article  CAS  PubMed  Google Scholar 

  • Sullivan-Bolyai JZ, Fife KH, Jacobs RF, Miller Z, Corey L (1983) Disseminated neonatal herpes simplex virus type 1 from a maternal breast lesion. Pediatrics 71:455–457

    CAS  PubMed  Google Scholar 

  • Tang S, Bosch-Marce M, Patel A, Margolis TP, Krause PR (2015) Characterization of herpes simplex virus 2 primary microRNA Transcript regulation. J Virol 89(9):4837–4848. doi:10.1128/JVI.03135-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thomas DL, Lock M, Zabolotny JM, Mohan BR, Fraser NW (2002) The 2-kilobase intron of the herpes simplex virus type 1 latency-associated transcript has a half-life of approximately 24 hours in SY5Y and COS-1 cells. J Virol 76(2):532–540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thompson RL, Sawtell NM (2001) Herpes simplex virus type 1 latency-associated transcript gene promotes neuronal survival. J Virol 75(14):6660–6675

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thompson RL, Preston CM, Sawtell NM (2009) De novo synthesis of VP16 coordinates the exit from HSV latency in vivo. PLoS Pathog 5(3), e1000352. doi:10.1371/journal.ppat.1000352

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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(7205):780–783. doi:10.1038/nature07103

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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(20):10677–10683. doi:10.1128/JVI.01185-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wagner EK, Bloom DC (1997) Experimental investigation of herpes simplex virus latency. Clin Microbiol Rev 10(3):419–443

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wagner EK, Devi RG, Feldman LT, Dobson AT, Zhang YF, Flanagan WM, Stevens JG (1988) Physical characterization of the herpes simplex virus latency-associated transcript in neurons. J Virol 62(4):1194–1202

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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(12):844–850

    Article  CAS  PubMed  Google Scholar 

  • Walz MA, Yamamoto H, Notkins AL (1976) Immunological response restricts number of cells in sensory ganglia infected with herpes simplex virus. Nature 264(5586):554–556

    Article  CAS  PubMed  Google Scholar 

  • Wang QY, Zhou C, Johnson KE, Colgrove RC, Coen DM, Knipe DM (2005) Herpesviral latency-associated transcript gene promotes assembly of heterochromatin on viral lytic-gene promoters in latent infection. Proc Natl Acad Sci U S A 102(44):16055–16059

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Watson Z, Dhummakupt A, Messer H, Phelan D, Bloom D (2013) Role of polycomb proteins in regulating HSV-1 latency. Viruses 5(7):1740–1757. doi:10.3390/v5071740

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wechsler SL, Nesburn AB, Watson R, Slanina SM, Ghiasi H (1988) Fine mapping of the latency-related gene of herpes simplex virus type 1: alternative splicing produces distinct latency-related RNAs containing open reading frames. J Virol 62(11):4051–4058

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wertheim JO, Smith MD, Smith DM, Scheffler K, Kosakovsky Pond SL (2014) Evolutionary origins of human herpes simplex viruses 1 and 2. Mol Biol Evol 31(9):2356–2364. doi:10.1093/molbev/msu185

    Article  PubMed  PubMed Central  Google Scholar 

  • Wheeler CE Jr, Cabrannis WH Jr (1965) Epidemic cutaneous herpes simplex in wrestlers (herpes gladiatorum). JAMA 194:993

    Article  PubMed  Google Scholar 

  • Whitley RJ (ed) (1989) Herpes simplex virus infections. Infectious diseases of the fetus and newborn infant. W.B. Saunders, Philadelphia

    Google Scholar 

  • Whitley RJ, Corey L, Arvin A (1988) Changing presentation of neonatal herpes simplex virus infection. J Infect Dis 158:109–116

    Article  CAS  PubMed  Google Scholar 

  • Wilcox CL, Johnson EM (1988) Characterization of nerve growth factor-dependent Herpes Simplex Latency in neurons in vitro. J Virol 62(2):393–399

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wilson AC, Mohr I (2012) A cultured affair: HSV latency and reactivation in neurons. Trends Microbiol 20(12):604–611. doi:10.1016/j.tim.2012.08.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wysocka J, Herr W (2003) The herpes simplex virus VP16-induced complex: the makings of a regulatory switch. Trends Biochem Sci 28(6):294–304

    Article  CAS  PubMed  Google Scholar 

  • Xu F, Sternberg MR, Kottiri BJ, McQuillan GM, Lee FK, Nahmias AJ, Berman SM, Markowitz LE (2006) Trends in herpes simplex virus type 1 and type 2 seroprevalence in the United States. JAMA 296(8):964–973

    Article  CAS  PubMed  Google Scholar 

  • Yang L, Voytek CC, Margolis TP (2000) Immunohistochemical analysis of primary sensory neurons latently infected with herpes simplex virus type 1. J Virol 74(1):209–217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(12):7373–7382

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yoshikawa T, Hill JM, Stanberry LR, Bourne N, Kurawadwala JF, Krause PR (1996) The characteristic site-specific reactivation phenotypes of HSV-1 and HSV-2 depend upon the latency-associated transcript region. J Exp Med 184(2):659–664

    Article  CAS  PubMed  Google Scholar 

  • Zhu J, Kang W, Marquart ME, Hill JM, Zheng X, Block TM, Fraser NW (1999) Identification of a novel 0.7 kb polyadenylated transcript in the LAT promoter region of HSV-1 that is strain specific and may contribute to virulence. Virology 265(2):296–307

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Thanks to Todd Margolis for images and Peterjon McAnany for help with the figures and to Nicole Giordani for help with the manuscript.

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  1. Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Box 100266, Gainesville, FL, 32610-0266, USA

    David C. Bloom & Adit Dhummakupt

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  1. David C. Bloom
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  2. Adit Dhummakupt
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Correspondence to David C. Bloom .

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  1. Departments of Biology and Neural Science, New York University, New York, New York, USA

    Carol Shoshkes Reiss

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Bloom, D.C., Dhummakupt, A. (2016). The Herpes Simplex Viruses. In: Reiss, C. (eds) Neurotropic Viral Infections. Springer, Cham. https://doi.org/10.1007/978-3-319-33189-8_4

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