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

Overview

Journal Infect Drug Resist

Publisher Dove Medical Press

Date 2021 Dec 22

PMID 34934329

Citations 5

Authors

Ying Zhang

Li-Si Zeng

Juan Wang

Wen-Qi Cai

Weiwen Cui

Tong-Jun Song

Xiao-Chun Peng

Zhaowu Ma

Ying Xiang

Shu-Zhong Cui

Hong-Wu Xin

Affiliations

Soon will be listed here.

Abstract

Herpes simplex viruses (HSVs) often cause latent infection for a lifetime, leading to repeated recurrence. HSVs have been engineered as oncolytic HSVs. The mechanism of the latent infection and recurrence remains largely unknown, which brings great challenges and limitations to eliminate HSVs in clinic and engineer safe oHSVs. Here, we systematically reviewed the latest development of the multi-step complex process of HSV latency and reactivation. Significantly, we first summarized the three HSV latent infection pathways, analyzed the structure and expression of the LAT1 and LAT2 of HSV-1 and HSV-2, proposed the regulation of LAT expression by four pathways, and dissected the function of LAT mediated by five LAT products of miRNAs, sRNAs, lncRNAs, sncRNAs and ORFs. We further analyzed that application of HSV LAT deletion mutants in HSV vaccines and oHSVs. Our review showed that deleting LAT significantly reduced the latency and reactivation of HSV, providing new ideas for the future development of safe and effective HSV therapeutics, vaccines and oHSVs. In addition, we proposed that RNA silencing or RNA interference may play an important role in HSV latency and reactivation, which is worth validating in future.

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References

Carpenter D, Henderson G, Hsiang C, Osorio N, BenMohamed L, Jones C . 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. 2007; 44(2):98-102. PMC: 2291025. DOI: 10.1016/j.micpath.2007.07.001. View

Rajcani J, Andrea V, Ingeborg R . Peculiarities of herpes simplex virus (HSV) transcription: an overview. Virus Genes. 2004; 28(3):293-310. DOI: 10.1023/b:viru.0000025777.62826.92. View

Tang S, Bertke A, Patel A, Wang K, Cohen J, Krause P . 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):10931-6. PMC: 2504787. DOI: 10.1073/pnas.0801845105. View

Tang S, Patel A, Krause P . 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. 2008; 83(3):1433-42. PMC: 2620902. DOI: 10.1128/JVI.01723-08. View

Qing G, Weili W, Fanqin Z, Rongchang Z, Yijin L, Jianqun D . Research of UL54-specific siRNA on herpes simplex virus type II replication. Int J Dermatol. 2011; 50(3):362-6. DOI: 10.1111/j.1365-4632.2010.04732.x. View

Harrison K, Zhu L, Thunuguntla P, Jones C . Herpes simplex virus 1 regulates β-catenin expression in TG neurons during the latency-reactivation cycle. PLoS One. 2020; 15(3):e0230870. PMC: 7105109. DOI: 10.1371/journal.pone.0230870. View

Yoshikawa T, Stanberry L, Bourne N, Krause P . 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):1535-41. PMC: 189975. DOI: 10.1128/JVI.70.3.1535-1541.1996. View

Ma J, Russell T, Spelman T, Carbone F, Tscharke D . 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. PMC: 4110040. DOI: 10.1371/journal.ppat.1004237. View

Ahmed M, Lock M, Miller C, Fraser N . 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. 2001; 76(2):717-29. PMC: 136840. DOI: 10.1128/jvi.76.2.717-729.2002. View

10.

Liu B, Robinson M, Han Z, Branston R, English C, Reay P . 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.3301885. View

11.

Lee J, Raja P, Knipe D . Herpesviral ICP0 Protein Promotes Two Waves of Heterochromatin Removal on an Early Viral Promoter during Lytic Infection. mBio. 2016; 7(1):e02007-15. PMC: 4725016. DOI: 10.1128/mBio.02007-15. View

12.

Kubat N, Amelio A, Giordani N, Bloom D . 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):12508-18. PMC: 525101. DOI: 10.1128/JVI.78.22.12508-12518.2004. View

13.

Andtbacka R, Kaufman H, Collichio F, Amatruda T, Senzer N, Chesney J . Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma. J Clin Oncol. 2015; 33(25):2780-8. DOI: 10.1200/JCO.2014.58.3377. View

14.

Cheng J, Wang L, Wang H, Tang F, Cai W, Sethi G . Insights into Biological Role of LncRNAs in Epithelial-Mesenchymal Transition. Cells. 2019; 8(10). PMC: 6829226. DOI: 10.3390/cells8101178. View

15.

Henderson G, Jaber T, Carpenter D, Wechsler S, Jones C . Identification of herpes simplex virus type 1 proteins encoded within the first 1.5 kb of the latency-associated transcript. J Neurovirol. 2010; 15(5-6):439-48. DOI: 10.3109/13550280903296353. View

16.

Liu X, Xin H, Lyu Y, Ma Z, Peng X, Xiang Y . Oncolytic herpes simplex virus tumor targeting and neutralization escape by engineering viral envelope glycoproteins. Drug Deliv. 2019; 25(1):1950-1962. PMC: 6282442. DOI: 10.1080/10717544.2018.1534895. View

17.

Borah S, Wong A, Steitz J . 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):2577-82. PMC: 2636732. DOI: 10.1073/pnas.0812826106. View

18.

Samoto K, Ehtesham M, Perng G, Hashizume K, Wechsler S, Nesburn A . A herpes simplex virus type 1 mutant with gamma 34.5 and LAT deletions effectively oncolyses human U87 glioblastomas in nude mice. Neurosurgery. 2002; 50(3):599-605; discussion 605-6. DOI: 10.1097/00006123-200203000-00031. View

19.

Liu Y, Yang H, Zhong F, Fan J . 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):782-91. DOI: 10.1111/ced.12671. View

20.

Zhang Y, Xin Q, Zhang J, Wang Y, Cheng J, Cai W . Transcriptional Regulation of Latency-Associated Transcripts (LATs) of Herpes Simplex Viruses. J Cancer. 2020; 11(11):3387-3399. PMC: 7097949. DOI: 10.7150/jca.40186. View