Multifunctional Non-Coding RNAs Mediate Latent Infection and Recurrence of Herpes Simplex Viruses

References

• Ying-ying Wang Y-NL, Xin H-Y, Xin H-Y. Identification of putative UL54 (ICP27) transcription regulatory sequences binding to Oct-1, v-Myb, Pax-6 and hairy in herpes simplex viruses. J Cancer. 2019;10(2):430–440. doi:10.7150/jca.2978730719137
   PubMed Web of Science ®Google Scholar
• Jones C. Alphaherpesvirus latency: its role in disease and survival of the virus in nature. Adv Virus Res. 1998;51(1):81–133. doi:10.1016/s0065-3527(08)60784-89891586
   PubMedGoogle Scholar
• BenMohamed L, Osorio N, Srivastava R, Khan AA, Simpson JL, Wechsler SL. 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 Neurovirol. 2015;21(5):508–517. doi:10.1007/s13365-015-0348-926002839
   PubMed Web of Science ®Google Scholar
• Kawamura Y, Bosch-Marce M, Tang S, Patel A, Krause PR. Herpes simplex virus 2 latency-associated transcript (LAT) region mutations do not identify a role for LAT-associated MicroRNAs in viral reactivation in guinea pig genital models. J Virol. 2018;92(14):89–181. doi:10.1128/JVI.00642-18
   Web of Science ®Google Scholar
• Yan C, Luo Z, Li W, et al. Disturbed Yin-Yang balance: stress increases the susceptibility to primary and recurrent infections of herpes simplex virus type 1. Acta pharmaceutica Sinica B. 2020;10(3):383–398. doi:10.1016/j.apsb.2019.06.00532140387
   PubMed Web of Science ®Google Scholar
• Xu X, Guo Y, Fan S, et al. Attenuated phenotypes and analysis of a herpes simplex virus 1 strain with partial deletion of the UL7, UL41 and LAT genes. Virol Sin. 2017;32(5):404–414. doi:10.1007/s12250-017-3947-128971351
   PubMed Web of Science ®Google Scholar
• Ma JZ, Russell TA, Spelman T, Carbone FR, Tscharke DC. Lytic gene expression is frequent in HSV-1 latent infection and correlates with the engagement of a cell-intrinsic transcriptional response. PLoS Pathog. 2014;10(7):e1004237. doi:10.1371/journal.ppat.100423725058429
   PubMed Web of Science ®Google Scholar
• Watanabe D, Goshima F. Oncolytic virotherapy by HSV. Adv Exp Med Biol. 2018;1045(4):63–84.29896663
   PubMed Web of Science ®Google Scholar
• Liu XQ, Xin HY, Lyu YN, et al. Oncolytic herpes simplex virus tumor targeting and neutralization escape by engineering viral envelope glycoproteins. Drug Deliv. 2018;25(1):1950–1962. doi:10.1080/10717544.2018.153489530799657
   PubMed Web of Science ®Google Scholar
• Zhang Y, Xin Q, Zhang JY, et al. Transcriptional regulation of latency-associated transcripts (LATs) of herpes simplex viruses. J Cancer. 2020;11(11):3387–3399. doi:10.7150/jca.4018632231745
   PubMed Web of Science ®Google Scholar
• Liu BM, Han ZQ, Branston RH, et al. ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties. Gene Ther. 2003;10(4):292–303. doi:10.1038/sj.gt.330188512595888
   PubMed Web of Science ®Google Scholar
• Andtbacka RHI, Kaufman HL, Frances C, et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015;33(25):2780–2788. doi:10.1200/JCO.2014.58.337726014293
   PubMed Web of Science ®Google Scholar
• Cabrera JR, Charron AJ, Leib DA. Neuronal subtype determines herpes simplex virus 1 latency-associated-transcript promoter activity during latency. J Virol. 2018;92(13):00430. doi:10.1128/JVI.00430-18
   Web of Science ®Google Scholar
• Raja P, Lee JS, Pan D, et al. Protein regulates the structure of latent viral chromatin. mBio. 2016;7(3):e00633–16. doi:10.1128/mBio.00633-1627190217
   PubMed Web of Science ®Google Scholar
• Lou W, Ji F, Fu J, Han Z, Di W, Zhang N. Retracted Article: transcriptional retargeting of herpes simplex virus for cell-specific replication to control cancer. J Cancer Res Clin Oncol. 2018;144(2):1–11. doi:10.1007/s00432-017-2566-429210001
   PubMed Web of Science ®Google Scholar
• Guo Q, Weng W, Zeng F, Zheng R, Luo Y, Du J. Research of UL54-specific siRNA on herpes simplex virus type II replication. Int J Dermatol. 2011;50(3):362–366. doi:10.1111/j.1365-4632.2010.04732.x21342172
   PubMed Web of Science ®Google Scholar
• Preston CM. Repression of viral transcription during herpes simplex virus latency. J General Virol. 2000;81(Pt 1):1–19.
   Google Scholar
• Sturm RA, Das G, Herr W. The ubiquitous octamer-binding protein Oct- 1 contains a POU domain with a homeo box subdomain. Genes Dev. 1988;2(12):1582. doi:10.1101/gad.2.12a.15822905684
   PubMed Web of Science ®Google Scholar
• Ryan AK, Rosenfeld MG. POU domain family values: flexibility, partnerships, and developmental codes. Genes Dev. 1997;11(10):1207. doi:10.1101/gad.11.10.12079171367
   PubMed Web of Science ®Google Scholar
• Herrera FJ, Triezenberg SJ. VP16-dependent association of chromatin-modifying coactivators and underrepresentation of histones at immediate-early gene promoters during herpes simplex virus infection. J Virol. 2004;78(18):9689–9696. doi:10.1128/JVI.78.18.9689-9696.200415331701
   PubMed Web of Science ®Google Scholar
• Kenyon C, Colebunders R, Hens N. Determinants of generalized herpes simplex virus-2 epidemics: the role of sexual partner concurrency. Int J STD AIDS. 2013;24(5):375–382. doi:10.1177/095646241247281623970705
   PubMed Web of Science ®Google Scholar
• Margolis TP, Yumi I, Li Y, Vicky V, Krause PR. 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. 2007;81(4):1872. doi:10.1128/JVI.02110-0617151134
   PubMed Web of Science ®Google Scholar
• Inman M, Perng GC, Henderson G, et al. Region of herpes simplex virus type 1 latency-associated transcript sufficient for wild-type spontaneous reactivation promotes cell survival in tissue culture. J Virol. 2001;75(8):3636–3646. doi:10.1128/JVI.75.8.3636-3646.200111264353
   PubMed Web of Science ®Google Scholar
• Perng GC, Jones C, Ciacci-Zanella J, et al. Virus-induced neuronal apoptosis blocked by the herpes simplex virus latency-associated transcript. Science. 2000;287(5457):1500–1503. doi:10.1126/science.287.5457.150010688801
   PubMed Web of Science ®Google Scholar
• Knipe DM, Lieberman PM, Jung JU, et al. Snapshots: chromatin control of viral infection. Virology. 2013;435(1):141–156. doi:10.1016/j.virol.2012.09.02323217624
   PubMed Web of Science ®Google Scholar
• Katz JP, Bodin ET, Coen DM. Quantitative polymerase chain reaction analysis of herpes simplex virus DNA in ganglia of mice infected with replication-incompetent mutants. J Virol. 1990;64(9):4288–4295. doi:10.1128/jvi.64.9.4288-4295.19902166818
   PubMed Web of Science ®Google Scholar
• Preston CM. Repression of viral transcription during herpes simplex virus latency. J Gen Virol. 2000;81(1):1–19. doi:10.1099/0022-1317-81-1-110640537
   PubMed Web of Science ®Google Scholar
• Sawtell NM. The probability of in vivo reactivation of herpes simplex virus type 1 increases with the number of latently infected neurons in the ganglia. J Virol. 1998;72(8):6888. doi:10.1128/JVI.72.8.6888-6892.19989658140
   PubMed Web of Science ®Google Scholar
• Lee DH, Ghiasi H. An M2 Rather than a TH2 Response Contributes to Better Protection against Latency Reactivation following Ocular Infection of Naive Mice with a Recombinant Herpes Simplex Virus 1 Expressing Murine Interleukin-4. J Virol. 2018;92(10):e00051–18. doi:10.1128/JVI.00051-1829491152
   PubMed Web of Science ®Google Scholar
• Lee JS, Raja P, Knipe DM. Herpesviral ICP0 protein promotes two waves of heterochromatin removal on an early viral promoter during lytic infection. mBio. 2016;7(1):e02007–15. doi:10.1128/mBio.02007-15
   PubMed Web of Science ®Google Scholar
• Lee JS, 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. Mbio. 2018;9(1):e02372–17. doi:10.1128/mBio.02372-1729437926
   PubMed Web of Science ®Google Scholar
• Henderson G, Jaber T, Carpenter D, Wechsler SL, Jones C. Identification of herpes simplex virus type 1 proteins encoded within the first 1.5 kb of the latency-associated transcript. J Neurovirol. 2009;15(5–6):439. doi:10.3109/1355028090329635320175695
   PubMed Web of Science ®Google Scholar
• Ahmed M, Lock M, Miller CG, Fraser NW. 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. 2002;76(2):717–729. doi:10.1128/JVI.76.2.717-729.200211752162
   PubMed Web of Science ®Google Scholar
• Doina A, Kent JR, Gartner JJ, Fraser NW. The stable 2-kb LAT intron of herpes simplex stimulates the expression of heat shock proteins and protects cells from stress. Virology. 2006;350(1):26–33. doi:10.1016/j.virol.2006.02.00116519918
   PubMed Web of Science ®Google Scholar
• Sumit B, Wong AC, Steitz JA. Drosophila hnRNP A1 homologs Hrp36/Hrp38 enhance U2-type versus U12-type splicing to regulate alternative splicing of the prospero twintron. Proc Natl Acad Sci U S A. 2009;106(8):2577–2582. doi:10.1073/pnas.081282610619196985
   PubMed Web of Science ®Google Scholar
• Xu X, Fan S, Zhou J, et al. The mutated tegument protein UL7 attenuates the virulence of herpes simplex virus 1 by reducing the modulation of alpha-4 gene transcription. Virol J. 2016;13(1):152. doi:10.1186/s12985-016-0600-927618986
   PubMed Web of Science ®Google Scholar
• Liu X-Q, Xin H-Y, Lyu Y-N, et al. Oncolytic herpes simplex virus tumor targeting and neutralization escape by engineering viral envelope glycoproteins. Drug Deliv. 2018;25(1):1950–1962.30799657
   PubMed Web of Science ®Google Scholar
• Diao L, Zhang B, Xuan C, et al. Activation of c-Jun N-terminal kinase (JNK) pathway by HSV-1 immediate early protein ICP0. Exp Cell Res. 2005;308(1):196–210. doi:10.1016/j.yexcr.2005.04.01615896775
   PubMed Web of Science ®Google Scholar
• Sumiko KS, Ryuichi K, Tokiko O, Saya N, Kenichi N, Hiroshi K. Neuronal injury-inducible gene is synergistically regulated by ATF3, c-Jun, and STAT3 through the interaction with Sp1 in damaged neurons. J Biol Chem. 2008;283(11):6988–6996. doi:10.1074/jbc.M70751420018192274
   PubMed Web of Science ®Google Scholar
• Dziennis S, Alkayed NJ. Role of signal transducer and activator of transcription 3 in neuronal survival and regeneration. Rev Neurosci. 2008;19(4–5):341–362. doi:10.1515/REVNEURO.2008.19.4-5.34119145989
   PubMed Web of Science ®Google Scholar
• Hunt D, Raivich G, Anderson PN. Activating transcription factor 3 and the nervous system. Front Mol Neurosci. 2012;5(7):548. doi:10.3389/fnmol.2012.00007
   Web of Science ®Google Scholar
• Takaya A, Naohide O, Wataru Y, Masaru R. Rapid and preferential induction of ATF3 transcription in response to low doses of UVA light. Biochem Biophys Res Commun. 2003;310(4):1168–1174. doi:10.1016/j.bbrc.2003.09.14314559238
   PubMed Web of Science ®Google Scholar
• Minfeng S, Te D, Grace Z, Bernard R. 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. Proc Natl Acad Sci U S A. 2015;112(39):E5420. doi:10.1073/pnas.151536911226305977
   PubMed Web of Science ®Google Scholar
• Millhouse S. ATF/CREB elements in the herpes simplex virus type 1 latency-associated transcript promoter interact with members of the ATF/CREB and AP-1 transcription factor families. J Biomed Sci. 1998;5(6):451–464. doi:10.1007/BF22559359845850
   PubMed Web of Science ®Google Scholar
• Washington SD, Edenfield SI, Lieux C, et al. Depletion of the insulator protein CTCF results in HSV-1 reactivation in vivo. J Virol. 2018;92(11):JVI.00173–18. doi:10.1128/JVI.00173-18
   Web of Science ®Google Scholar
• Hafezi W, Lorentzen EU, Eing BR, 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. PLoS Pathog. 2012;8(5):e1002679. doi:10.1371/journal.ppat.100267922589716
   PubMed Web of Science ®Google Scholar
• Cliffe AR, Garber DA, Knipe DM. Transcription of the herpes simplex virus latency-associated transcript promotes the formation of facultative heterochromatin on lytic promoters. J Virol. 2009;83(16):8182. doi:10.1128/JVI.00712-0919515781
   PubMed Web of Science ®Google Scholar
• Cliffe AR, Coen DM, Knipe DM. Kinetics of facultative heterochromatin and polycomb group protein association with the herpes simplex viral genome during establishment of latent infection. mBio. 2013;4(1):169–172. doi:10.1128/mBio.00590-12
   Web of Science ®Google Scholar
• Washington SD, Musarrat F, Ertel MK, Backes GL, Neumann DM. CTCF binding sites in the herpes simplex virus 1 genome display site-specific CTCF occupation, protein recruitment, and insulator function. J Virol. 2018;92(8):e00156–18. doi:10.1128/JVI.00156-1829437965
   PubMed Web of Science ®Google Scholar
• Peng W, Vitvitskaia OD, Wechsler S, Jones C. Identification of two small RNAs within the first 1.5-kb of the herpes simplex virus type 1-encoded latency-associated transcript. J Neurovirol. 2008;14(1):41–52. doi:10.1080/1355028070179395718300074
   PubMed Web of Science ®Google Scholar
• Ambros V, microRNAs: tiny regulators with great potential. Cell. 2001;107(7):823–826. doi:10.1016/S0092-8674(01)00616-X11779458
   PubMed Web of Science ®Google Scholar
• Liu Y, Yang HL, Zhong FF, Fan JY. Anti-apoptotic function of herpes simplex virus −2 latency-associated transcript RL1 sequence and screening of its encoded microRNAs. Clin Exp Dermatol. 2016;41(7):782–791. doi:10.1111/ced.1267127663158
   PubMed Web of Science ®Google Scholar
• 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 Neurovirol. 2015;21(2):199–209. doi:10.1007/s13365-015-0319-125645379
   PubMed Web of Science ®Google Scholar
• Tang S, Patel Akrause PR. 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. 2009;83(3):1433–1442. doi:10.1128/JVI.01723-0819019961
   PubMed Web of Science ®Google Scholar
• Jennifer Lin U, Kramer MF, Igor J, Karnowski HW, Coen DM, Cullen BR. MicroRNAs expressed by herpes simplex virus 1 during latent infection regulate viral mRNAs. Nature. 2008;454(7205):780. doi:10.1038/nature0710318596690
   PubMed Web of Science ®Google Scholar
• Jiang X, Brown D, Osorio N, Hsiang C, BenMohamed L, Wechsler SL. 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. 2016;22(1):38–49. doi:10.1007/s13365-015-0362-y26069184
   PubMed Web of Science ®Google Scholar
• Duan F, Liao J, Huang Q, Nie Y, Wu K. HSV-1 miR-H6 inhibits HSV-1 replication and IL-6 expression in human corneal epithelial cells in vitro. Clin Dev Immunol. 2012;2012(6):192791. doi:10.1155/2012/19279122550533
   PubMedGoogle Scholar
• Shuang T, Bertke AS, Amita P, Kening W, Cohen JI, Krause PR. An acutely and latently expressed herpes simplex virus 2 viral microRNA inhibits expression of ICP34.5, a viral neurovirulence factor. Proc Natl Acad Sci U S A. 2008;105(31):10931–10936. doi:10.1073/pnas.080184510518678906
   PubMed Web of Science ®Google Scholar
• Tang S, Bosch-Marce M, Patel A, Margolis TP, Krause PR. Characterization of HSV-2 primary miRNA transcript regulation. J Virol. 2015;85(2):261–265.
   Google Scholar
• Ahmed M, Lock M, Miller CG, Fraser NW. 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. 2002;76(2):717–729.11752162
   PubMed Web of Science ®Google Scholar
• Xianzhi J, Aziz Alami C, Chinhui H, et al. The herpes simplex virus type 1 latency-associated transcript can protect neuron-derived C1300 and Neuro2A cells from granzyme B-induced apoptosis and CD8 T-cell killing. J Virol. 2011;85(5):2325. doi:10.1128/JVI.01791-1021177822
   PubMed Web of Science ®Google Scholar
• Chowdhury D, Lieberman J. Death by a thousand cuts: granzyme pathways of programmed cell death. Annu Rev Immunol. 2008;26(1):389–420. doi:10.1146/annurev.immunol.26.021607.09040418304003
   PubMed Web of Science ®Google Scholar
• Pardo J, Aguilo JI, Anel A, et al. The biology of cytotoxic cell granule exocytosis pathway: granzymes have evolved to induce cell death and inflammation. Microbes Infect. 2009;11(4):452–459. doi:10.1016/j.micinf.2009.02.00419249384
   PubMed Web of Science ®Google Scholar
• Gupta A, Gartner JJ, Sethupathy P, Hatzigeorgiou AG, Fraser NW. Anti-apoptotic function of a microRNA encoded by the HSV-1 latency-associated transcript. Nature. 2006;442(7098):82. doi:10.1038/nature0483616738545
   PubMed Web of Science ®Google Scholar
• Derynck R, Akhurst RJ, Balmain A. TGF-beta signaling in tumor suppression and cancer progression. Nat Genet. 2001;29(2):117–129. doi:10.1038/ng1001-11711586292
   PubMed Web of Science ®Google Scholar
• Khvorova A, Kwak Y-G, Tamkun M, Majerfeld I, Yarus M. RNAs that bind and change the permeability of phospholipid membranes. Proc Natl Acad Sci U S A. 1999;96(19):10649–10654. doi:10.1073/pnas.96.19.1064910485880
   PubMed Web of Science ®Google Scholar
• Wenwen S, Mariana SES, Tareq J, et al. 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. 2009;83(18):9131–9139. doi:10.1128/JVI.00871-0919587058
   PubMed Web of Science ®Google Scholar
• Carpenter D, Henderson G, Hsiang C, et al. Introducing point mutations into the ATGs of the putative open reading frames of the HSV-1 gene encoding the latency associated transcript (LAT) reduces its anti-apoptosis activity. Microb Pathog. 2008;44(2):98–102. doi:10.1016/j.micpath.2007.07.00117900852
   PubMed Web of Science ®Google Scholar
• Cheng JT, Wang L, Wang H, et al. Insights into biological role of LncRNAs in epithelial-mesenchymal transition. Cells. 2019;8(10):1178. doi:10.3390/cells8101178
   PubMed Web of Science ®Google Scholar
• Watson ZL, Washington SD, Phelan DM, et al. In vivo knock-down of the HSV-1 latency-associated transcript reduces reactivation from latency. J Virol. 2018;21:JVI.00812–18.
   Google Scholar
• Allen SJ, Antje RK, Mott KR, et al. Interactions between herpesvirus entry mediator (TNFRSF14) and latency-associated transcript during herpes simplex virus 1 latency. J Virol. 2014;88(4):1961. doi:10.1128/JVI.02467-1324307582
   PubMed Web of Science ®Google Scholar
• Kubat NJ. The herpes simplex virus type 1 latency-associated transcript (LAT) enhancer/rcr Is hyperacetylated during latency independently of LAT transcription. J Virol. 2004;78(22):12508–12518. doi:10.1128/JVI.78.22.12508-12518.200415507638
   PubMed Web of Science ®Google Scholar
• Leticia Frizzo DS, Clinton J. Small non-coding RNAs encoded within the herpes simplex virus type 1 latency associated transcript (LAT) cooperate with the retinoic acid inducible gene I (RIG-I) to induce beta-interferon promoter activity and promote cell survival. Virus Res. 2013;175(2):101–109. doi:10.1016/j.virusres.2013.04.00523648811
   PubMed Web of Science ®Google Scholar
• Hobbs WE, Brough DE, Kovesdi I, Deluca NA. Efficient activation of viral genomes by levels of herpes simplex virus ICP0 insufficient to affect cellular gene expression or cell survival. J Virol. 2001;75(7):3391–3403. doi:10.1128/JVI.75.7.3391-3403.200111238865
   PubMed Web of Science ®Google Scholar
• Thomas SK, Lilley CE, Latchman DS, Coffin RS. A protein encoded by the herpes simplex virus (HSV) type 1 2-kilobase latency-associated transcript is phosphorylated, localized to the nucleus, and overcomes the repression of expression from exogenous promoters when inserted into the quiescent HSV genome. J Virol. 2002;76(8):4056–4067. doi:10.1128/JVI.76.8.4056-4067.200211907244
   PubMed Web of Science ®Google Scholar
• Perng GC, Ab GHN, Wechsler SL, Slanina SM. A 371-nucleotide region between the herpes simplex virus type 1 (HSV-1) LAT promoter and the 2-kilobase LAT is not essential for efficient spontaneous reactivation of latent HSV-1. J Virol. 1996;70(3):2014–2018. doi:10.1128/jvi.70.3.2014-2018.19968627728
   PubMed Web of Science ®Google Scholar
• Rajčáni J, Andrea V, Ingeborg R. Peculiarities of herpes simplex virus (HSV) transcription: an overview. Virus Genes. 2004;28(3):293. doi:10.1023/B:VIRU.0000025777.62826.9215266111
   PubMed Web of Science ®Google Scholar
• Thomas S, Gough G, Coffin R, S. R. 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. 1999;73(8):6618–6625. doi:10.1128/JVI.73.8.6618-6625.199910400759
   PubMed Web of Science ®Google Scholar
• Washington SD, Singh P, Johns RN, et al. The CCCTC binding factor, CTRL2, modulates heterochromatin deposition and the establishment of HSV-1 latency in vivo. J Virol. 2019;93(13):e00415–19. doi:10.1128/JVI.00415-1930996085
   PubMed Web of Science ®Google Scholar
• Jin L, Perng G-C, Mott KR, et al. 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. 2005;79(19):12286–12295. doi:10.1128/JVI.79.19.12286-12295.200516160155
   PubMed Web of Science ®Google Scholar
• Mott KR, Osorio N, Jin L, et al. The bovine herpesvirus-1 LR ORF2 is critical for this gene’s ability to restore the high wild-type reactivation phenotype to a herpes simplex virus-1 LAT null mutant. J Gen Virol. 2003;84(11):2975–2985. doi:10.1099/vir.0.19421-014573802
   PubMed Web of Science ®Google Scholar
• Carpenter D, Singh S, Osorio N, et al. A speculated ribozyme site in the herpes simplex virus type 1 latency-associated transcript gene is not essential for a wild-type reactivation phenotype. J Neurovirol. 2008;14(6):558–562. doi:10.1080/1355028080227591218982533
   PubMed Web of Science ®Google Scholar
• Harrison KS, Zhu L, Thunuguntla P, Jones C. Herpes simplex virus 1 regulates beta-catenin expression in TG neurons during the latency-reactivation cycle. PLoS One. 2020;15(3):e0230870. doi:10.1371/journal.pone.023087032226020
   PubMed Web of Science ®Google Scholar
• Watson ZL, Washington SD, Phelan DM, et al. In vivo knockdown of the herpes simplex virus 1 latency-associated transcript reduces reactivation from latency. J Virol. 2018;92(16):e00812–18. doi:10.1128/JVI.00812-1829875240
   PubMed Web of Science ®Google Scholar
• Yoshikawa T, Stanberry LR, Bourne N, Krause PR. Downstream regulatory elements increase acute and latent herpes simplex virus type 2 latency-associated transcript expression but do not influence recurrence phenotype or establishment of latency. J Virol. 1996;70(3):1535–1541. doi:10.1128/jvi.70.3.1535-1541.19968627672
   PubMed Web of Science ®Google Scholar
• Samoto KEM. Perng GC. A Herpes simplex virus type 1 mutant with γ34.5 and LAT deletions effectively oncolyses human U87 glioblastomas in nude mice. Neurosurgery. 2002;50(3):599–606.11841729
   PubMed Web of Science ®Google Scholar
• Samoto K, Perng GC, Ehtesham M, et al. A herpes simplex virus type 1 mutant deleted for γ34.5 and LAT kills glioma cells in vitro and is inhibited for in vivo reactivation. Cancer Gene Ther. 2001;8(4):269–277. doi:10.1038/sj.cgt.770030611393279
   PubMed Web of Science ®Google Scholar
• Ragab EI, Yoshinori N, Itzel B-V, et al. Genomic signature of the natural oncolytic herpes simplex virus HF10 and its therapeutic role in preclinical and clinical trials. Front Oncol. 2017;7(1):149–156. doi:10.3389/fonc.2017.0014928770166
   PubMedGoogle Scholar
• Hirooka Y, Kasuya H, Ishikawa T, et al. A Phase I clinical trial of EUS-guided intratumoral injection of the oncolytic virus, HF10 for unresectable locally advanced pancreatic cancer. BMC Cancer. 2018;18(1):596. doi:10.1186/s12885-018-4453-z29801474
   PubMed Web of Science ®Google Scholar
• Schang LM, Hossain A, Jones C. The latency-related gene of bovine herpesvirus 1 encodes a product which inhibits cell cycle progression. J Virol. 1996;70(6):3807–3814. doi:10.1128/jvi.70.6.3807-3814.19968648716
   PubMed Web of Science ®Google Scholar
• Doerig C, Pizer LI, Wilcox CL. An antigen encoded by the latency-associated transcript in neuronal cell cultures latently infected with herpes simplex virus type 1. J Virol. 1991;65(5):2724–2727. doi:10.1128/jvi.65.5.2724-2727.19911850045
   PubMed Web of Science ®Google Scholar
• Wang S, Ljubimov AV, Jin L, Pfeffer K, Kronenberg M, Ghiasi H. Herpes simplex virus 1 latency and the kinetics of reactivation are regulated by a complex network of interactions between the herpesvirus entry mediator, its ligands (gD, BTLA, LIGHT, and CD160), and the latency-associated transcript. J Virol. 2018;92(24):01451. doi:10.1128/JVI.01451-18
   Web of Science ®Google Scholar
• Pourchet A, Modrek AS, Placantonakis DG, Mohr I, Wilson AC. Modeling HSV-1 latency in human embryonic stem cell-derived neurons. Pathogens. 2017;6(2):2076–2817. doi:10.3390/pathogens6020024
   Web of Science ®Google Scholar
• Jiang X, Chentoufi AA, Hsiang C, et al. The herpes simplex virus type 1 latency-associated transcript can protect neuron-derived C1300 and Neuro2A cells from granzyme B-induced apoptosis and CD8 T-cell killing. J Virol. 2011;85(5):2325.21177822
   PubMed Web of Science ®Google Scholar
• Kati T, Sariah A, Kevin M, et al. The latency-associated transcript inhibits apoptosis via downregulation of components of the type I interferon pathway during latent herpes simplex virus 1 ocular infection. J Virol. 2019;93(10):e00103–19. doi:10.1128/JVI.00103-1930814286
   PubMed Web of Science ®Google Scholar
• Peng W, Benmohamed L, Perng GC, et al. The locus encompassing the latency-associated transcript of herpes simplex virus type 1 interferes with and delays interferon expression in productively infected neuroblastoma cells and trigeminal Ganglia of acutely infected mice. J Virol. 2005;79(10):6162–6171. doi:10.1128/JVI.79.10.6162-6171.200515858001
   PubMed Web of Science ®Google Scholar
• Jaggi U, Matundan HH, Tormanen K, Wang S, Ghiasi H. Expression of murine CD80 by HSV-1 in place of LAT can compensate for latency-reactivation and anti-apoptotic functions of LAT. J Virol. 2019;94(6):e01798–19.
   Web of Science ®Google Scholar
• Mott KR, Bresee CJ, Allen SJ, Benmohamed L, Wechsler SL, Ghiasi H. Level of herpes simplex virus type 1 latency correlates with severity of corneal scarring and exhaustion of CD8+ T cells in trigeminal ganglia of latently infected mice. J Virol. 2009;83(5):2246–2254. doi:10.1128/JVI.02234-0819091870
   PubMed Web of Science ®Google Scholar
• Stanfield B, Kousoulas KG. Herpes simplex vaccines: prospects of live-attenuated HSV vaccines to combat genital and ocular infections. Curr Clin Microbiol Rep. 2015;2(3):125–136. doi:10.1007/s40588-015-0020-427114893
   PubMedGoogle Scholar
• Johnston C, Gottlieb SL, Wald A. Status of vaccine research and development of vaccines for herpes simplex virus. Vaccine. 2016;34(26):2948–2952. doi:10.1016/j.vaccine.2015.12.07626973067
   PubMed Web of Science ®Google Scholar
• Guo Z, Li Y, Ding SW, Small RN. A-based antimicrobial immunity. Nat Rev Immunol. 2019;19(1):31–44. doi:10.1038/s41577-018-0071-x30301972
   PubMed Web of Science ®Google Scholar
• Li Y, Lu J, Han Y, Fan X, Ding SW. RNA interference functions as an antiviral immunity mechanism in mammals. Science. 2013;342(6155):231–234. doi:10.1126/science.124191124115437
   PubMed Web of Science ®Google Scholar