Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

ACC 2024 Congress

Catch up on all the top stories and latest evidence in cardiology research with our ACC 2024 Congress hub page.
ADVANCED SEARCH
Log in
Top
Virology Journal
Published in: Virology Journal 1/2020

Open Access 01-12-2020 | Herpes Virus | Research

Novel transcription regulatory sequences and factors of the immune evasion protein ICP47 (US12) of herpes simplex viruses

Authors: Jun-Ting Cheng, Ying-Ying Wang, Lin-Zhong Zhu, Ying Zhang, Wen-Qi Cai, Zi-Wen Han, Yang Zhou, Xian-Wang Wang, Xiao-Chun Peng, Ying Xiang, Hui-Yu Yang, Shu-Zhong Cui, Zhaowu Ma, Bing-Rong Liu, Hong-Wu Xin

Published in: Virology Journal | Issue 1/2020

Login to get access

Abstract

Background

Herpes simplex virus (HSV) can cause encephalitis. Its infected cell polypeptide 47 (ICP47), encoded by immediate-early gene US12, promotes immune escape. ICP47 was modified in the clinically approved oncolytic HSV (oHSV) T-Vec. However, transcription regulatory sequence (TRS) and transcription regulatory factor (TRF) of HSV US12 are seldom reported.

Methods

Previously, our laboratory isolated a new HSV strain named HSV-1-LXMW from a male patient with oral herpes in Beijing, China. Firstly, the genetic tree was used to analyze its genetic relationship. The US12 TRS and TRF in HSV-1-LXMW were found by using predictive software. Secondly, the further verification by the multi-sequence comparative analysis shown that the upstream DNA sequence of HSV US12 gene contained the conserved region. Finally, the results of literature search shown that the expression of transcription factors was related to the tissue affinity of HSV-1 and HSV-2, so as to increase the new understanding of the transcriptional regulation of HSV biology and oncolytic virus (OVs) therapy.

Results

Here we reported the transcriptional regulation region sequence of our new HSV-1-LXMW, and its close relationship with HSV-1-CR38 and HSV-1-17. Importantly we identified eight different kinds of novel TRSs and TRFs of HSV US12 for the first time, and found they are conserved among HSV-1 (c-Rel, Elk-1, Pax-4), HSV-2 (Oct-1, CF2-II, E74A, StuAp) or both HSVs (HNF-4). The TRFs c-Rel and Oct-1 are biologically functional respectively in immune escape and viral replication during HSV infection.

Conclusions

Our findings have important implication to HSV biology, infection, immunity and oHSVs.
Appendix
Available only for authorised users
Literature
1.
Ellison LM, Man Y, Stojadinovic A, Xin H, Avital I. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in treatment of gastric cancer with peritoneal carcinomatosis. Chin J Cancer Res. 2017;29:86–92.PubMedPubMedCentral
2.
Liu Y, Yu C, Wu Y, Sun X, Su Q, You C, Xin H. CD44(+) fibroblasts increases breast cancer cell survival and drug resistance via IGF2BP3-CD44-IGF2 signalling. J Cell Mol Med. 2017;21:1979–88.PubMedPubMedCentral
3.
Xin HW, Ambe CM, Ray S, Kim BK, Koizumi T, Wiegand GW, Hari D, Mullinax JE, Jaiswal KR, Garfield SH, et al. Wnt and the cancer niche: paracrine interactions with gastrointestinal cancer cells undergoing asymmetric cell division. J Cancer. 2013;4:447–57.PubMedPubMedCentral
4.
Xin HW, Ambe CM, Hari DM, Wiegand GW, Miller TC, Chen JQ, Anderson AJ, Ray S, Mullinax JE, Koizumi T, et al. Label-retaining liver cancer cells are relatively resistant to sorafenib. Gut. 2013;62:1777–86.PubMedPubMedCentral
5.
Xin HW, Ambe CM, Miller TC, Chen JQ, Wiegand GW, Anderson AJ, Ray S, Mullinax JE, Hari DM, Koizumi T, et al. Liver label retaining Cancer cells are relatively resistant to the reported anti-Cancer stem cell drug metformin. J Cancer. 2016;7:1142–51.PubMedPubMedCentral
6.
Hari D, Xin HW, Jaiswal K, Wiegand G, Kim BK, Ambe C, Burka D, Koizumi T, Ray S, Garfield S, et al. Isolation of live label-retaining cells and cells undergoing asymmetric cell division via nonrandom chromosomal cosegregation from human cancers. Stem Cells Dev. 2011;20:1649–58.PubMedPubMedCentral
7.
Liu XQ, Xin HY, Lyu YN, Ma ZW, Peng XC, Xiang Y, Wang YY, Wu ZJ, Cheng JT, Ji JF, et al. Oncolytic herpes simplex virus tumor targeting and neutralization escape by engineering viral envelope glycoproteins. Drug Deliv. 2018;25:1950–62.PubMedPubMedCentral
8.
9.
Lawler SE, Speranza MC, Cho CF, Chiocca EA. Oncolytic viruses in Cancer treatment: a review. JAMA Oncol. 2017;3:841–9.PubMed
10.
Puzanov I, Milhem MM, Minor D, Hamid O, Li A, Chen L, Chastain M, Gorski KS, Anderson A, Chou J, et al. Talimogene Laherparepvec in combination with Ipilimumab in previously untreated, Unresectable stage IIIB-IV melanoma. J Clin Oncol. 2016;34:2619–26.PubMedPubMedCentral
11.
Poh A. First Oncolytic viral therapy for melanoma. Cancer Discov. 2016;6:6.PubMed
12.
Agarwalla PK, Aghi MK. Oncolytic herpes simplex virus engineering and preparation. Methods Mol Biol. 2012;797:1–19.PubMed
13.
Dai X, Zhou ZH. Structure of the herpes simplex virus 1 capsid with associated tegument protein complexes. Science. 2018;360.
14.
15.
Duan J, Liuzzi M, Paris W, Liard F, Browne A, Dansereau N, Simoneau B, Faucher AM, Cordingley MG. Oral bioavailability and in vivo efficacy of the helicase-primase inhibitor BILS 45 BS against acyclovir-resistant herpes simplex virus type 1. Antimicrob Agents Chemother. 2003;47:1798–804.PubMedPubMedCentral
16.
Bernstock JD, Vicario N, Li R, Nan L, Totsch SK, Schlappi C, Gessler F, Han X, Parenti R, Beierle EA, et al. Safety and efficacy of oncolytic HSV-1 G207 inoculated into the cerebellum of mice. Cancer Gene Ther. 2019.
17.
18.
Todo T, Martuza RL, Rabkin SD, Johnson PA. Oncolytic herpes simplex virus vector with enhanced MHC class I presentation and tumor cell killing. Proc Natl Acad Sci. 2001;98:6396–401.PubMed
19.
Whitley RJ, Roizman B. Herpes simplex virus infections. Lancet. 2001;357:1513–8.PubMed
20.
Praest P, Luteijn RD, Brak-Boer IGJ, Lanfermeijer J, Hoelen H, Ijgosse L, Costa AI, Gorham RD, Lebbink RJ, Wiertz EJHJ. The influence of TAP1 and TAP2 gene polymorphisms on TAP function and its inhibition by viral immune evasion proteins. Mol Immunol. 2018;101:55–64.PubMed
21.
Oldham ML, Hite RK, Steffen AM, Damko E, Li Z, Walz T, Chen J. A mechanism of viral immune evasion revealed by cryo-EM analysis of the TAP transporter. Nature. 2016;529:537–40.PubMedPubMedCentral
22.
Matschulla T, Berry R, Gerke C, Döring M, Busch J, Paijo J, Kalinke U, Momburg F, Hengel H, Halenius A. A highly conserved sequence of the viral TAP inhibitor ICP47 is required for freezing of the peptide transport cycle. Sci Rep. 2017;7.
23.
Liu R, Varghese S, Rabkin SD. Oncolytic herpes simplex virus vector therapy of breast cancer in C3(1)/SV40 T-antigen transgenic mice. Cancer Res. 2005;65:1532–40.PubMed
24.
Messerli SM, Prabhakar S, Tang Y, Mahmood U, Giovannini M, Weissleder R, Bronson R, Martuza R, Rabkin S, Breakefield XO. Treatment of schwannomas with an oncolytic recombinant herpes simplex virus in murine models of neurofibromatosis type 2. Hum Gene Ther. 2006;17:20–30.PubMed
25.
Fukuhara H, Martuza RL, Rabkin SD, Ito Y, Todo T. Oncolytic herpes simplex virus vector g47delta in combination with androgen ablation for the treatment of human prostate adenocarcinoma. Clin Cancer Res. 2005;11:7886–90.PubMed
26.
Raafat N, Sadowski-Cron C, Mengus C, Heberer M, Spagnoli GC, Zajac P. Preventing vaccinia virus class-I epitopes presentation by HSV-ICP47 enhances the immunogenicity of a TAP-independent cancer vaccine epitope. Int J Cancer. 2012;131:E659–69.PubMed
27.
Scaria A, Sullivan JA, St. George JA, Kaplan JM, Lukason MJ, Morris JE, Plog M, Nicolette C, Gregory RJ, Wadsworth SC. Adenoviral vector expressing ICP47 inhibits adenovirus-specific cytotoxic T lymphocytes in nonhuman primates. Mol Ther. 2000;2:505–14.PubMed
28.
S O, FJ H, JR D, A H, S M, WS L, SJ T: Phosphorylation of the VP16 transcriptional activator protein during herpes simplex virus infection and mutational analysis of putative phosphorylation sites. Virology 2006, 345:468–481.
29.
Suk H, Knipe DM. Proteomic analysis of the herpes simplex virus 1 virion protein 16 transactivator protein in infected cells. Proteomics. 2015;15:1957–67.PubMed
30.
Wang YY, Lyu YN, Xin HY, Cheng JT, Liu XQ, Wang XW, Peng XC, Xiang Y, Xin VW, Lu CB, et al. 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;10:430–40.PubMedPubMedCentral
31.
Mancini M, Caignard G, Charbonneau B, Dumaine A, Wu N, Leiva-Torres GA, Gerondakis S, Pearson A, Qureshi ST, Sladek R, Vidal SM. Rel-dependent immune and central nervous system mechanisms control viral replication and inflammation during mouse herpes simplex encephalitis. J Immunol. 2019;202:1479–93.PubMed
32.
SL S, J H, PM P: Differential regulation of the HIV-1 LTR by specific NF-kappa B subunits in HSV-1-infected cells. Virology 1996, 224:214–223.
33.
Nogueira ML, Wang VE, Tantin D, Sharp PA, Kristie TM. Herpes simplex virus infections are arrested in Oct-1-deficient cells. Proc Natl Acad Sci U S A. 2004;101:1473–8.PubMedPubMedCentral
34.
Akhova O, Bainbridge M, Misra V. The neuronal host cell factor-binding protein Zhangfei inhibits herpes simplex virus replication. J Virol. 2005;79:14708–18.PubMedPubMedCentral
35.
V M, S W, P Y, S H, P OH: Conformational alteration of Oct-1 upon DNA binding dictates selectivity in differential interactions with related transcriptional coactivators. Mol Cell Biol 1996, 16:4404–4413.
36.
Advani SJ, Durand LO, Weichselbaum RR, Roizman B. Oct-1 is posttranslationally modified and exhibits reduced capacity to bind cognate sites at late times after infection with herpes simplex virus 1. J Virol. 2003;77:11927–32.PubMedPubMedCentral
37.
RF G, P OH: Sequence, function, and regulation of the Vmw65 gene of herpes simplex virus type 2. J Virol 1991, 65:6705–6713.
38.
Mancini M, Caignard G, Charbonneau B, Dumaine A, Wu N: Rel-Dependent Immune and Central Nervous System Mechanisms Control Viral Replication and Inflammation during Mouse Herpes Simplex Encephalitis 2019, 202:1479–1493.
39.
40.
Ducker C, Chow LKY, Saxton J, Handwerger J, McGregor A, Strahl T, Layfield R, Shaw PE. De-ubiquitination of ELK-1 by USP17 potentiates mitogenic gene expression and cell proliferation. Nucleic Acids Res. 2019;47:4495–508.PubMedPubMedCentral
41.
Sakata N, Yoshimatsu G, Kodama S. Development and characteristics of pancreatic epsilon cells. Int J Mol Sci. 2019;20.
42.
Hwang SS, Kim LK, Lee GR, Flavell RA. Role of OCT-1 and partner proteins in T cell differentiation. Biochim Biophys Acta. 2016;1859:825–31.PubMed
43.
Tsukamoto D, Ito M, Takamatsu N. HNF-4 participates in the hibernation-associated transcriptional regulation of the chipmunk hibernation-related protein gene. Sci Rep. 2017;7:44279.PubMedPubMedCentral
44.
Gogos JA, Hsu T, Bolton J, Kafatos FC. Sequence discrimination by alternatively spliced isoforms of a DNA binding zinc finger domain. Science. 1992;257:1951–5.PubMed
45.
Sun W, Wang CF, Zhang Z. Transcription factor E74A affects the ecdysone titer by regulating the expression of the EO gene in the silkworm, Bomby mori. Biochim Biophys Acta Gen Subj. 2017;1861:551–8.PubMed
46.
Zhao Y, Su H, Zhou J, Feng H, Zhang KQ, Yang J. The APSES family proteins in fungi: characterizations, evolution and functions. Fungal Genet Biol. 2015;81:271–80.PubMed
47.
Zhang J, Wang K, Wang S, Zheng C. Herpes simplex virus 1 E3 ubiquitin ligase ICP0 protein inhibits tumor necrosis factor alpha-induced NF-kappaB activation by interacting with p65/RelA and p50/NF-kappaB1. J Virol. 2013;87:12935–48.PubMedPubMedCentral
48.
Wang K, Ni L, Wang S, Zheng C. Herpes simplex virus 1 protein kinase US3 hyperphosphorylates p65/RelA and dampens NF-kappaB activation. J Virol. 2014;88:7941–51.PubMedPubMedCentral
49.
Wang D, Wang XW, Peng XC, Xiang Y, Song SB, Wang YY, Chen L, Xin VW, Lyu YN, Ji J, et al. CRISPR/Cas9 genome editing technology significantly accelerated herpes simplex virus research. Cancer Gene Ther. 2018;25:93–105.PubMed
50.
Killock D. Skin cancer: T-VEC oncolytic viral therapy shows promise in melanoma. Nat Rev Clin Oncol. 2015;12:438.PubMed
51.
Johnson DB, Puzanov I, Kelley MC. Talimogene laherparepvec (T-VEC) for the treatment of advanced melanoma. Immunotherapy. 2015;7:611–9.PubMedPubMedCentral
52.
Andtbacka R, Collichio F, Amatruda T, Senzer N, Chesney J, Delman K, Spitler L, Puzanov I, Doleman S, Ye Y, et al. OPTiM: a multicenter, randomized phase 3 trial of Talimogene Laherparepvec versus subcutaneous GM-CSF for the treatment of Unresected stage IIIB/C and IV melanoma. J der Deutschen Dermatologischen Gesellschaft. 2013;11:8–8.
53.
Grigg C, Blake Z, Gartrell R, Sacher A, Taback B, Saenger Y. Talimogene laherparepvec (T-Vec) for the treatment of melanoma and other cancers. Semin Oncol. 2016;43:638–46.PubMed
54.
Shao W, Chen X, Samulski RJ, Hirsch ML, Li C. Inhibition of antigen presentation during AAV gene therapy using virus peptides. Hum Mol Genet. 2018;27:601–13.PubMed
55.
Wang P, Kan Q, Yu Z, Li L, Zhang Z, Pan X, Feng T. Recombinant adenovirus expressing ICP47 gene suppresses the ability of dendritic cells by restricting specific T cell responses. Cell Immunol. 2013;282:129–35.PubMed
Metadata
Title
Novel transcription regulatory sequences and factors of the immune evasion protein ICP47 (US12) of herpes simplex viruses
Authors
Jun-Ting Cheng
Ying-Ying Wang
Lin-Zhong Zhu
Ying Zhang
Wen-Qi Cai
Zi-Wen Han
Yang Zhou
Xian-Wang Wang
Xiao-Chun Peng
Ying Xiang
Hui-Yu Yang
Shu-Zhong Cui
Zhaowu Ma
Bing-Rong Liu
Hong-Wu Xin
Publication date
01-12-2020
Publisher
BioMed Central
Keyword
Herpes Virus
Published in
Virology Journal / Issue 1/2020
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/s12985-020-01365-3

Other articles of this Issue 1/2020

Virology Journal 1/2020 Go to the issue

Research

Prevalence of human papillomavirus genotypes and precancerous cervical lesions in a screening population in Beijing, China: analysis of results from China’s top 3 hospital, 2009–2019

Research

Evaluation of a new point-of-care oral anti-HCV test for screening of hepatitis C virus infection

Research

Characterization of accessory genes in coronavirus genomes

Research

Human pegivirus (HPgV, GBV-C) RNA in volunteer blood donors from a public hemotherapy service in Northern Brazil

Research

Investigation of the immunogenicity of Zika glycan loop

Research

Characterization of HIV-1 uncoating in human microglial cell lines

ACC 2024 Congress Coverage

Cardiology Video

Highlights from the ACC 2024 Congress

Watch now

Watch official videos from the ACC congress summarizing key highlights from the last year in heart failure, cardiomyopathies, valvular disease, pulmonary vascular disease, and pediatric cardiology.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits