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J Zhejiang Univ (Med Sci)  2019, Vol. 48 Issue (1): 89-101    DOI: 10.3785/j.issn.1008-9292.2019.02.14
    
Mechanisms of herpes simplex virus latency and reactivation
SUN Boqiang(),WANG Qiongyan,PAN Dongli()
Department of Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou 310058, China
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Abstract  

Herpes simplex virus (HSV), including HSV-1 and HSV-2, is an important pathogen that can cause many diseases. Usually these diseases are recurrent and incurable. After lytic infection on the surface of peripheral mucosa, HSV can enter sensory neurons and establish latent infection during which viral replication ceases. Moreover, latent virus can re-enter the replication cycle by reactivation and return to peripheral tissues to start recurrent infection. This ability to escape host immune surveillance during latent infection and to spread during reactivation is a viral survival strategy and the fundamental reason why no drug can completely eradicate the virus at present. Although there are many studies on latency and reactivation of HSV, and much progress has been made, many specific mechanisms of the process remain obscure or even controversial due to the complexity of this process and the limitations of research models. This paper reviews the major results of research on HSV latency and reactivation, and discusses future research directions in this field.



Key wordsSimplexvirus      Infection      Gene expression      Trigeminal ganglion      In situ hybridization      Transcriptional activation      Immunohistochemistry      Review     
Received: 23 September 2018      Published: 10 May 2019
CLC:  R373.9  
Corresponding Authors: PAN Dongli     E-mail: boqiangsun@163.com;pandongli@zju.edu.cn
Cite this article:

SUN Boqiang,WANG Qiongyan,PAN Dongli. Mechanisms of herpes simplex virus latency and reactivation. J Zhejiang Univ (Med Sci), 2019, 48(1): 89-101.

URL:

http://www.zjujournals.com/med/10.3785/j.issn.1008-9292.2019.02.14     OR     http://www.zjujournals.com/med/Y2019/V48/I1/89


单纯疱疹病毒潜伏和激活机制研究进展

单纯疱疹病毒(HSV,包括HSV-1和HSV-2)是引起多种疾病的重要病原,通常这些疾病具有反复发作和无法根治的特点。HSV在外周黏膜组织表面进行增殖式感染后,可进入感觉神经元并建立无复制的潜伏感染。潜伏的病毒还可以通过激活的方式重新进入复制周期,并回到外周组织进行复发感染。这种既能通过潜伏逃避宿主免疫攻击又能在激活过程中传播的能力是该病毒高超的生存策略,也是当前任何药物无法彻底消灭该病毒的根本原因。虽然HSV潜伏与激活的研究众多,且不断有新的研究进展,但由于潜伏和激活过程本身的复杂性和研究模型的局限性,其中很多具体过程相关机制依然不明确,甚至常有争议。本文重点梳理HSV-1潜伏和激活的主要研究成果,并讨论其发展趋势。


关键词: 单纯疱疹病毒属,  感染,  基因表达,  三叉神经节,  原位杂交,  转录激活,  免疫组织化学,  综述 
Figure 1 Establishment of latency and reactivation of herpes simplex virus in neurons
[1]   DOLAN A , JAMIESON F E , CUNNINGHAM C , et al . The genome sequence of herpes simplex virus type 2[J]. J Virol,1998,72:2010-2021.
[2]   ROIZMAN B K D M , WHITLEY R J . Herpes simplex viruses[M]//KNIPE D M H P, GRIFFIN D E. Fields virology. Philadelphia: Lippincott Williams & Wilkins,2007:2501-2601.
[3]   BERNSTEIN D I , BELLAMY A R , HOOK E W , et al . Epidemiology, clinical presentation, and antibody response to primary infection with herpes simplex virus type 1 and type 2 in young women[J]. Clin Infect Dis,2013,56(3):344-351.
[4]   LOOKER K J , MAGARET A S , MAY M T ,et al . Global and regional estimates of prevalent and incident herpes simplex virus type 1 infections in 2012[ J/OL ]. PLoS One,2015,10(10):e0140765.
[5]   LOOKER K J , MAGARET A S , TURNER K M , et al . Global estimates of prevalent and incident herpes simplex virus type 2 infections in 2012[ J/OL ]. PLoS One,2015,10(1):e114989.
[6]   LOOKER K J , MAGARET A S , MAY M T, et al . First estimates of the global and regional incidence of neonatal herpes infection[J]. Lancet Glob Health,2017,5(3):e300-e309.
[7]   FAROOQ A V , SHUKLA D . Herpes simplex epithelial and stromal keratitis: an epidemiologic update[J]. Surv Ophthalmol,2012,57(5):448-462.
[8]   MICHALICOVá A , BHIDE K , BHIDE M , et al . How viruses infiltrate the central nervous system[J]. Acta Virol,2017,61(4):393-400.
[9]   WHITLEY R J . Herpes simplex virus infections of the central nervous system[J]. Continuum (Minneap Minn),2015,21(6 Neuroinfectious Disease):1704-1713.
[10]   PHELAN D , BARROZO E R , BLOOM D C . HSV1 latent transcription and non-coding RNA: a critical retrospective[J]. J Neuroimmunol,2017,308:65-101.
[11]   NICOLL M P , PROEN?A J T , EFSTATHIOU S . The molecular basis of herpes simplex virus latency[J]. FEMS Microbiol Rev,2012,36(3):684-705.
[12]   RANDALL G , LAGUNOFF M , ROIZMAN B . Herpes simplex virus 1 open reading frames O and P are not necessary for establishment of latent infection in mice[J]. J Virol,2000,74(19):9019-9027.
[13]   CHEN S H , LEE L Y, GARBER D A , et al . Neither LAT nor open reading frame P mutations increase expression of spliced or intron-containing ICP0 transcripts in mouse ganglia latently infected with herpes simplex virus[J]. J Virol,2002,76(10):4764-4772.
[14]   GALLOWAY D A , FENOGLIO C , SHEVCHUK M , et al . Detection of herpes simplex RNA in human sensory ganglia[J]. Virology,1979,95(1):265-268.
[15]   STEVENS J G , WAGNER E K , DEVI-RAO G B , et al . RNA complementary to a herpesvirus alpha gene mRNA is prominent in latently infected neurons[J]. Science,1987,235(4792):1056-1059.
[16]   LANFRANCA M P , MOSTAFA H H , DAVIDO D J . HSV-1 ICP0: an E3 ubiquitin ligase that counteracts host intrinsic and innate immunity[J]. Cells,2014,3(2):438-454.
[17]   JAVIER R T , STEVENS J G , DISSETTE V B , et al . A herpes simplex virus transcript abundant in latently infected neurons is dispensable for establishment of the latent state[J]. Virology,1988,166(1):254-257.
[18]   SEDARATI F , IZUMI K M , WAGNER E K , et al . Herpes simplex virus type 1 latency-associated transcription plays no role in establishment or maintenance of a latent infection in murine sensory neurons[J]. J Virol,1989,63(10):4455-4458.
[19]   STEINER I , SPIVACK J G , LIRETTE R P , et al . Herpes simplex virus type 1 latency-associated transcripts are evidently not essential for latent infection[J]. EMBO J,1989,8(2):505-511.
[20]   MADOR N , GOLDENBERG D , COHEN O , et al . Herpes simplex virus type 1 latency-associated transcripts suppress viral replication and reduce immediate-early gene mRNA levels in a neuronal cell line[J]. J Virol,1998,72(6):5067-5075.
[21]   BURTON E A , HONG C S , GLORIOSO J C . 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]. J Virol,2003,77(6):3516-3530.
[22]   CHEN S H , KRAMER M F , SCHAFFER P A , et al . A viral function represses accumulation of transcripts from productive-cycle genes in mouse ganglia latently infected with herpes simplex virus[J]. J Virol,1997,71(8):5878-5884.
[23]   GARBER D A , SCHAFFER P A , KNIPE D M . A LAT-associated function reduces productive-cycle gene expression during acute infection of murine sensory neurons with herpes simplex virus type 1[J]. J Virol,1997,71(8):5885-5893.
[24]   NICOLL M P , HANN W , SHIVKUMAR M , et al . The HSV-1 latency-associated transcript functions to repress latent phase lytic gene expression and suppress virus reactivation from latently infected neurons[J/OL]. PLoS Pathog,2016,12(4):e1005539.
[25]   CLIFFE A R , GARBER D A , KNIPE D M . Transcription of the herpes simplex virus latency-associated transcript promotes the formation of facultative heterochromatin on lytic promoters[J]. J Virol,2009,83(16):8182-8190.
[26]   WANG Q Y , ZHOU C , JOHNSON K E , et al . Herpesviral latency-associated transcript gene promotes assembly of heterochromatin on viral lytic-gene promoters in latent infection[J]. Proc Natl Acad Sci U S A,2005,102(44):16055-16059.
[27]   GIORDANI N V , NEUMANN D M , KWIATKOWSKI D L , et al . 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]. J Virol,2008,82(12):6056-6060.
[28]   LEIB D A , BOGARD C L , KOSZ-VNENCHAK M , et al . A deletion mutant of the latency-associated transcript of herpes simplex virus type 1 reactivates from the latent state with reduced frequency[J]. J Virol,1989,63(7):2893-2900.
[29]   TROUSDALE M D , STEINER I , SPIVACK J G , et al . In vivo and in vitro reactivation impairment of a herpes simplex virus type 1 latency-associated transcript variant in a rabbit eye model[J]. J Virol,1991,65(12):6989-6993.
[30]   BLOCK T M , DESHMANE S , MASONIS J , et al . An HSV LAT null mutant reactivates slowly from latent infection and makes small plaques on CV-1 monolayers[J]. Virology,1993,192(2):618-630.
[31]   PERNG G C , DUNKEL E C , GEARY P A , et al . 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]. J Virol,1994,68(12):8045-8055.
[32]   PERNG G C , SLANINA S M , YUKHT A , et al . The latency-associated transcript gene enhances establishment of herpes simplex virus type 1 latency in rabbits[J]. J Virol,2000,74(4):1885-1891.
[33]   THOMPSON R L , SAWTELL N M . Herpes simplex virus type 1 latency-associated transcript gene promotes neuronal survival[J]. J Virol,2001,75(14):6660-6675.
[34]   SAWTELL N M , POON D K , TANSKY C S , et al . The latent herpes simplex virus type 1 genome copy number in individual neurons is virus strain specific and correlates with reactivation[J]. J Virol,1998,72(7):5343-5350.
[35]   HOSHINO Y , PESNICAK L , STRAUS S E , et al . 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[J]. Virology,2009,387(1):193-199.
[36]   O'NEIL J E , LOUTSCH J M , AGUILAR J S , et al . 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]. J Virol,2004,78(10):5038-5044.
[37]   WATSON Z L , WASHINGTON S D , PHELAN D M , et al . In vivo knockdown of the herpes simplex virus 1 latency-associated transcript reduces reactivation from latency[J/OL]. J Virol,2018,92(16):pii:e00812-18.
[38]   PERNG G C , JONES C , CIACCI-ZANELLA J , et al . Virus-induced neuronal apoptosis blocked by the herpes simplex virus latency-associated transcript[J]. Science,2000,287(5457):1500-1503.
[39]   PERNG G C , MAGUEN B , JIN L , et al . 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]. J Virol,2002,76(3):1224-1235.
[40]   THOMPSON R L , SAWTELL N M . Herpes simplex virus type 1 latency-associated transcript gene promotes neuronal survival[J]. J Virol,2001,75(14):6660-6675.
[41]   HAMZA M A , HIGGINS D M , FELDMAN L T , et al . The latency-associated transcript of herpes simplex virus type 1 promotes survival and stimulates axonal regeneration in sympathetic and trigeminal neurons[J]. J Neurovirol,2007,13(1):56-66.
[42]   THOMPSON R L , SAWTELL N M . The herpes simplex virus type 1 latency associated transcript locus is required for the maintenance of reactivation competent latent infections[J]. J Neurovirol,2011,17(6):552-558.
[43]   NICOLL M P , PROEN?A J T , CONNOR V , et al . Influence of herpes simplex virus 1 latency-associated transcripts on the establishment and maintenance of latency in the ROSA26R reporter mouse model[J]. J Virol,2012,86(16):8848-8858.
[44]   CUI C , GRIFFITHS A , LI G , et al . Prediction and identification of herpes simplex virus 1-encoded microRNAs[J]. J Virol,2006,80(11):5499-5508.
[45]   UMBACH J L , KRAMER M F , JURAK I , et al . MicroRNAs expressed by herpes simplex virus 1 during latent infection regulate viral mRNAs[J]. Nature,2008,454(7205):780-783.
[46]   JURAK I , KRAMER M F , MELLOR J C , et al . Numerous conserved and divergent microRNAs expressed by herpes simplex viruses 1 and 2[J]. J Virol,2010,84(9):4659-4672.
[47]   TANG S , BERTKE A S , PATEL A , et al . An acutely and latently expressed herpes simplex virus 2 viral microRNA inhibits expression of ICP34.5, a viral neurovirulence factor[J]. Proc Natl Acad Sci U S A,2008,105(31):10931-10936.
[48]   TANG S , PATEL A , KRAUSE P R . 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]. J Virol,2009,83(3):1433-1442.
[49]   KRAMER M F , JURAK I , PESOLA J M , et al . Herpes simplex virus 1 microRNAs expressed abundantly during latent infection are not essential for latency in mouse trigeminal ganglia[J]. Virology,2011,417(2):239-247.
[50]   DU T , HAN Z , ZHOU G , et al . Patterns of accumulation of miRNAs encoded by herpes simplex virus during productive infection,latency, and on reactivation[J/OL]. Proc Natl Acad Sci U S A,2015,112(1):E49
-E 55.
[51]   JURAK I , HACKENBERG M , KIM J Y, et al . Expression of herpes simplex virus 1 microRNAs in cell culture models of quiescent and latent infection[J]. J Virol,2014,88(4):2337-2339.
[52]   COKARI? B M , ZUBKOVI? A , FEREN?I? A , et al . Herpes simplex virus 1 miRNA sequence variations in latently infected human trigeminal ganglia[J]. Virus Res,2018,256:90-95.
[53]   PAN D , PESOLA J M , LI G , et al . Mutations inactivating herpes simplex virus 1 microRNA miR-H2 do not detectably increase ICP0 gene expression in infected cultured cells or mouse trigeminal ganglia[J/OL]. J Virol,2017,91(2):pii:e02001-16.
[54]   FLORES O , NAKAYAMA S , WHISNANT A W , et al . Mutational inactivation of herpes simplex virus 1 microRNAs identifies viral mRNA targets and reveals phenotypic effects in culture[J]. J Virol,2013,87(12):6589-6603.
[55]   JIANG X , BROWN D , OSORIO N , et al . A herpes simplex virus type 1 mutant disrupted for microRNA H2 with increased neurovirulence and rate of reactivation[J]. J Neurovirol,2015,21(2):199-209.
[56]   SCHERER J , YAFFE Z A , VERSHININ M , et al . Dual-color herpesvirus capsids discriminate inoculum from progeny and reveal axonal transport dynamics[J]. J Virol,2016,90(21):9997-10006.
[57]   AGGARWAL A , MIRANDA-SAKSENA M , BOADLE R A , et al . Ultrastructural visualization of individual tegument protein dissociation during entry of herpes simplex virus 1 into human and rat dorsal root ganglion neurons[J]. J Virol,2012,86(11):6123-6137.
[58]   HAFEZI W , LORENTZEN E U , EING B R , et al . Entry of herpes simplex virus type 1 (HSV-1) into the distal axons of trigeminal neurons favors the onset of nonproductive, silent infection[J/OL]. PLoS Pathog,2012,8(5):e1002679.
[59]   SAWTELL N M , THOMPSON R L . De novo herpes simplex virus VP16 expression gates a dynamic programmatic transition and sets the latent/lytic balance during acute infection in trigeminal ganglia[J/OL]. PLoS Pathog,2016,12(9):e1005877.
[60]   HAGMANN M , GEORGIEV O , SCHAFFNER W , et al . Transcription factors interacting with herpes simplex virus alpha gene promoters in sensory neurons[J]. Nucleic Acids Res,1995,23(24):4978-4985.
[61]   KOLB G , KRISTIE T M . Association of the cellular coactivator HCF-1 with the Golgi apparatus in sensory neurons[J]. J Virol,2008,82(19):9555-9563.
[62]   LILLYCROP K A , DENT C L , WHEATLEY S C , et al . The octamer-binding protein Oct-2 represses HSV immediate-early genes in cell lines derived from latently infectable sensory neurons[J]. Neuron,1991,7(3):381-390.
[63]   PROEN?A J T , COLEMAN H M , CONNOR V , et al . A historical analysis of herpes simplex virus promoter activation in vivo reveals distinct populations of latently infected neurones[J]. J Gen Virol,2008,89(Pt 12):2965-2974.
[64]   PROEN?A J T , COLEMAN H M , NICOLL M P , et al . An investigation of herpes simplex virus promoter activity compatible with latency establishment reveals VP16-independent activation of immediate-early promoters in sensory neurones[J]. J Gen Virol,2011,92(Pt 11):2575-2585.
[65]   PAN D , FLORES O , UMBACH J L , et al . A neuron-specific host microRNA targets herpes simplex virus-1 ICP0 expression and promotes latency[J]. Cell Host Microbe,2014,15(4):446-456.
[66]   SHU M , DU T , ZHOU G , et al . Role of activating transcription factor 3 in the synthesis of latency-associated transcript and maintenance of herpes simplex virus 1 in latent state in ganglia[J/OL]. Proc Natl Acad Sci U S A,2015,112(39):E5420 -E5426.
[67]   MARGOLIS T P , IMAI Y , YANG L , et al . 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]. J Virol,2007,81(4):1872-1878.
[68]   BERTKE A S , SWANSON S M , CHEN J , et al . A5-positive primary sensory neurons are nonpermissive for productive infection with herpes simplex virus 1 in vitro [J]. J Virol,2011,85(13):6669-6677.
[69]   IMAI Y , APAKUPAKUL K , KRAUSE P R , et al . Investigation of the mechanism by which herpes simplex virus type 1 LAT sequences modulate preferential establishment of latent infection in mouse trigeminal ganglia[J]. J Virol,2009,83(16):7873-7882.
[70]   DESHMANE S L , FRASER N W . During latency, herpes simplex virus type 1 DNA is associated with nucleosomes in a chromatin structure[J]. J Virol,1989,63(2):943-947.
[71]   CLIFFE A R , COEN D M , KNIPE D M . Kinetics of facultative heterochromatin and polycomb group protein association with the herpes simplex viral genome during establishment of latent infection[J/OL]. MBio,2013,4(1):pii:e00590-12.
[72]   KNIPE D M , CLIFFE A . Chromatin control of herpes simplex virus lytic and latent infection[J]. Nat Rev Microbiol,2008,6(3):211-221.
[73]   KWIATKOWSKI D L , THOMPSON H W , BLOOM D C . The polycomb group protein Bmi1 binds to the herpes simplex virus 1 latent genome and maintains repressive histone marks during latency[J]. J Virol,2009,83(16):8173-8181.
[74]   BLOOM D C , GIORDANI N V , KWIATKOWSKI D L . Epigenetic regulation of latent HSV-1 gene expression[J]. Biochim Biophys Acta,2010,1799(3-4):246-256.
[75]   KUBAT N J , AMELIO A L , GIORDANI N V , et al . The herpes simplex virus type 1 latency-associated transcript (LAT) enhancer/rcr is hyperacetylated during latency independently of LAT transcription[J]. J Virol,2004,78(22):12508-12518.
[76]   KUBAT N J , TRAN R K , MCANANY P , et al . Specific histone tail modification and not DNA methylation is a determinant of herpes simplex virus type 1 latent gene expression[J]. J Virol,2004,78(3):1139-1149.
[77]   NEUMANN D M , BHATTACHARJEE P S , GIORDANI N V , et al . 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]. J Virol,2007,81(23):13248-13253.
[78]   AMELIO A L , GIORDANI N V , KUBAT N J , et al . 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]. J Virol,2006,80(4):2063-2068.
[79]   KRISTIE T M , LIANG Y , VOGEL J L . Control of alpha-herpesvirus IE gene expression by HCF-1 coupled chromatin modification activities[J]. Biochim Biophys Acta,2010,1799(3-4):257-265.
[80]   LEE J S, RAJA P , KNIPE D M . Herpesviral ICP0 protein promotes two waves of heterochromatin removal on an early viral promoter during lytic infection[J/OL]. MBio,2016,7(1):pii:e02007-15.
[81]   RAJA P , LEE J S, PAN D , et al . A herpesviral lytic protein regulates the structure of latent viral chromatin[J/OL]. MBio,2016,7(3):pii:e00633-16.
[82]   FERENCZY M W , DELUCA N A . Reversal of heterochromatic silencing of quiescent herpes simplex virus type 1 by ICP0[J]. J Virol,2011,85(7):3424-3435.
[83]   LEE J S, RAJA P , PAN D , et al . CCCTC-binding factor acts as a heterochromatin barrier on herpes simplex viral latent chromatin and contributes to poised latent infection[J/OL]. MBio,2018,9(1):pii:e02372-17.
[84]   THEIL D , DERFUSS T , PARIPOVIC I , et al . Latent herpesvirus infection in human trigeminal ganglia causes chronic immune response[J]. Am J Pathol,2003,163(6):2179-2184.
[85]   LIU T , TANG Q , HENDRICKS R L . Inflammatory infiltration of the trigeminal ganglion after herpes simplex virus type 1 corneal infection[J]. J Virol,1996,70(1):264-271.
[86]   KNICKELBEIN J E , KHANNA K M , YEE M B, et al . Noncytotoxic lytic granule-mediated CD8+ T cell inhibition of HSV-1 reactivation from neuronal latency[J]. Science,2008,322(5899):268-271.
[87]   KHANNA K M , BONNEAU R H , KINCHINGTON P R , et al . Herpes simplex virus-specific memory CD8+ T cells are selectively activated and retained in latently infected sensory ganglia[J]. Immunity,2003,18(5):593-603.
[88]   ST L A J, PETERS B , SIDNEY J , et al . Defining the herpes simplex virus-specific CD8+ T cell repertoire in C57BL/6 mice[J]. J Immunol,2011,186(7):3927-3933.
[89]   FRANK G M , LEPISTO A J , FREEMAN M L , et al . Early CD4(+) T cell help prevents partial CD8(+) T cell exhaustion and promotes maintenance of herpes simplex virus 1 latency[J]. J Immunol,2010,184(1):277-286.
[90]   LI L , LI Z , WANG E , et al . Herpes simplex virus 1 infection of tree shrews differs from that of mice in the severity of acute infection and viral transcription in the peripheral nervous system[J]. J Virol,2016,90(2):790-804.
[91]   MARGOLIS T P , ELFMAN F L , LEIB D , et al . Spontaneous reactivation of herpes simplex virus type 1 in latently infected murine sensory ganglia[J]. J Virol,2007,81(20):11069-11074.
[92]   MA J Z, RUSSELL T A , SPELMAN T , et al . Lytic gene expression is frequent in HSV-1 latent infection and correlates with the engagement of a cell-intrinsic transcriptional response[J/OL]. PLoS Pathog,2014,10(7):e1004237.
[93]   VELZEN M VAN , JING L , OSTERHAUS A D , et al . Local CD4 and CD8 T-cell reactivity to HSV-1antigens documents broad viral protein expression and immune competence in latently infected human trigeminal ganglia[J/OL]. PLoS Pathog,2013,9(8):e1003547.
[94]   RUSSELL T A , TSCHARKE D C . Lytic promoters express protein during herpes simplex virus latency[J]. PLoS Pathog,2016,12(6):e1005729.
[95]   KOSZ-VNENCHAK M , JACOBSON J , COEN D M , et al . Evidence for a novel regulatory pathway for herpes simplex virus gene expression in trigeminal ganglion neurons[J]. J Virol,1993,67(9):5383-5393.
[96]   HALFORD W P , KEMP C D , ISLER J A , Et al . 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]. J Virol,2001,75(13):6143-6153.
[97]   HALFORD W P , SCHAFFER P A . ICP0 is required for efficient reactivation of herpes simplex virus type 1 from neuronal latency[J]. J Virol,2001,75(7):3240-3249.
[98]   CAI W , ASTOR T L , LIPTAK L M , et al . The herpes simplex virus type 1 regulatory protein ICP0 enhances virus replication during acute infection and reactivation from latency[J]. J Virol,1993,67(12):7501-7512.
[99]   THOMPSON R L , SAWTELL N M . Evidence that the herpes simplex virus type 1 ICP0 protein does not initiate reactivation from latency in vivo [J]. J Virol,2006,80(22):10919-10930.
[100]   SAWTELL N M , THOMPSON R L , HAAS R L . Herpes simplex virus DNA synthesis is not a decisive regulatory event in the initiation of lytic viral protein expression in neurons in vivo during primary infection or reactivation from latency[J]. J Virol,2006,80(1):38-50.
[101]   THOMPSON R L , PRESTON C M , SAWTELL N M . De novo synthesis of VP16 coordinates the exit from HSV latency in vivo [J/OL]. PLoS Pathog,2009,5(3):e1000352.
[102]   KIM J Y, MANDARINO A , CHAO M V , et al . Transient reversal of episome silencing precedes VP16-dependent transcription during reactivation of latent HSV-1 in neurons[J/OL]. PLoS Pathog,2012,8(2):e1002540.
[103]   WHITLOW Z , KRISTIE T M . 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]. J Virol,2009,83(18):9591-9595.
[104]   LIANG Y , VOGEL J L , NARAYANAN A , et al . Inhibition of the histone demethylase LSD1 blocks alpha-herpesvirus lytic replication and reactivation from latency[J]. Nat Med,2009,15(11):1312-1317.
[105]   ALFONSO-DUNN R , TURNER A W , JEAN B P M , et al . Transcriptional elongation of HSV immediate early genes by the super elongation complex drives lytic infection and reactivation from latency[J]. Cell Host Microbe,2017,21(4):507-517.e5.
[106]   WILCOX C L , JOHNSON E M . Nerve growth factor deprivation results in the reactivation of latent herpes simplex virus in vitro [J]. J Virol,1987,61(7):2311-2315.
[107]   CAMARENA V , KOBAYASHI M , KIM J Y, et al . Nature and duration of growth factor signaling through receptor tyrosine kinases regulates HSV-1 latency in neurons[J]. Cell Host Microbe,2010,8(4):320-330.
[108]   WASHINGTON S D , EDENFIELD S I , LIEUX C , et al . Depletion of the insulator protein CTCF results in HSV-1 reactivation in vivo [J/OL]. J Virol,2018,92(11):pii:e00173-18.
[109]   NAGAMINE M , SHIMIZU Y . Effects of personal controls on cortisol secretion during stress processes[J]. Shinrigaku Kenkyu,2003,74(2):164-170.
[110]   DJORDJEVI? J , CVIJI? G , DAVIDOVI? V . Different activation of ACTH and corticosterone release in response to various stressors in rats[J]. Physiol Res,2003,52(1):67-72.
[111]   HUANG W , XIE P , XU M , et al . The influence of stress factors on the reactivation of latent herpes simplex virus type 1 in infected mice[J]. Cell Biochem Biophys,2011,61(1):115-122.
[112]   BENMOHAMED L , OSORIO N , SRIVASTAVA R , et al . Decreased reactivation of a herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) mutant using the in vivo mouse UV-B model of induced reactivation[J]. J Neurovirol,2015,21(5):508-517.
[113]   SAINZ B , LOUTSCH J M , MARQUART M E , et al . Stress-associated immunomodulation and herpes simplex virus infections[J]. Med Hypotheses,2001,56(3):348-356.
[114]   KOOK I , JONES C . The serum and glucocorticoid-regulated protein kinases (SGK) stimulate bovine herpesvirus 1 and herpes simplex virus 1 productive infection[J]. Virus Res,2016,222:106-112.
[115]   SINANI D , CORDES E , WORKMAN A , et al . Stress-induced cellular transcription factors expressed in trigeminal ganglionic neurons stimulate the herpes simplex virus 1 ICP0 promoter[J]. J Virol,2013,87(23):13042-13047.
[116]   CLIFFE A R , ARBUCKLE J H , VOGEL J L , et al . Neuronal stress pathway mediating a histone methyl/phospho switch is required for herpes simplex virus reactivation[J]. Cell Host Microbe,2015,18(6):649-658.
[117]   WAGNER E K , BLOOM D C . Experimental investigation of herpes simplex virus latency[J]. Clin Microbiol Rev,1997,10(3):419-443.
[118]   BENMOHAMED L , OSORIO N , KHAN A A , et al . Prior corneal scarification and injection of immune serum are not required before ocular HSV-1 infection for UV-B-induced virus reactivation and recurrent herpetic corneal disease in latently infected mice[J]. Curr Eye Res,2016,41(6):747-756.
[119]   SAWTELL N M , THOMPSON R L . Rapid in vivo reactivation of herpes simplex virus in latently infected murine ganglionic neurons after transient hyperthermia[J]. J Virol,1992,66(4):2150-2156.
[120]   DASGUPTA G , BENMOHAMED L . Of mice and not humans: how reliable are animal models for evaluation of herpes CD8(+)-T cell-epitopes-based immunotherapeutic vaccine candidates?[J]. Vaccine,2011,29(35):5824-5836.
[121]   KWON B S , GANGAROSA L P , BURCH K D , et al . Induction of ocular herpes simplex virus shedding by iontophoresis of epinephrine into rabbit cornea[J]. Invest Ophthalmol Vis Sci,1981,21(3):442-449.
[122]   WEBRE J M , HILL J M , NOLAN N M , et al . Rabbit and mouse models of HSV-1 latency, reactivation, and recurrent eye diseases[J]. J Biomed Biotechnol,2012,2012:612316.
[123]   AL-DUJAILI L J , CLERKIN P P , CLEMENT C , et al . Ocular herpes simplex virus: how are latency, reactivation, recurrent disease and therapy interrelated?[J]. Future Microbiol,2011,6(8):877-907.
[124]   HILL J M , RAYFIELD M A , HARUTA Y . Strain specificity of spontaneous and adrenergically induced HSV-1 ocular reactivation in latently infected rabbits[J]. Curr Eye Res,1987,6(1):91-97.
[125]   PRESTON C M , MABBS R , NICHOLL M J . Construction and characterization of herpes simplex virus type 1 mutants with conditional defects in immediate early gene expression[J]. Virology,1997,229(1):228-239.
[126]   MCMAHON R , WALSH D . Efficient quiescent infection of normal human diploid fibroblasts with wild-type herpes simplex virus type 1[J]. J Virol,2008,82(20):10218-10230.
[127]   DANAHER R J , JACOB R J , MILLER C S . Establishment of a quiescent herpes simplex virus type 1 infection in neurally-differentiated PC12 cells[J]. J Neurovirol,1999,5(3):258-267.
[128]   WILCOX C L , SMITH R L , FREED C R , et al . Nerve growth factor-dependence of herpes simplex virus latency in peripheral sympathetic and sensory neurons in vitro [J]. J Neurosci,1990,10(4):1268-1275.
[129]   KATZENELL S , CABRERA J R , NORTH B J , et al . Isolation, purification, and culture of primary murine sensory neurons[J]. Methods Mol Biol,2017,1656:229-251.
[130]   CH'NG T H , ENQUIST L W . Neuron-to-cell spread of pseudorabies virus in a compartmented neuronal culture system[J]. J Virol,2005,79(17):10875-10889.
[131]   KOYUNCU O O , MACGIBENY M A , HOGUE I B , et al . Compartmented neuronal cultures reveal two distinct mechanisms for alpha herpesvirus escape from genome silencing[J/OL]. PLoS Pathog,2017,13(10):e1006608.
[132]   KOYUNCU O O , SONG R , GRECO T M , et al . The number of alphaherpesvirus particles infecting axons and the axonal protein repertoire determines the outcome of neuronal infection[J/OL]. MBio,2015,6(2):pii:e00276-15.
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