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Hsv microRNAs

Yoshiki Kawamura, Marta Bosch-Marce, Shuang Tang, Amita Patel, Philip R Krause
Despite the long-standing observation that herpes simplex virus (HSV) Latency-Associated Transcript (LAT) promoter-deletion viruses show impaired recurrence phenotypes in relevant animal models, the mechanism by which these sequences exert this phenotypic effect is unknown. We constructed and evaluated four mutant HSV-2 viruses with targeted mutations in the LAT promoter and LAT-associated miRNAs affecting (1) the LAT TATA box, (2) the LAT ICP4-binding site, (3) miR-I and miR-II (miR-I/II), which both target ICP34...
May 2, 2018: Journal of Virology
Afsar R Naqvi, Alexandra Seal, Jennifer Shango, Maria Brambila Navarette, Gloria Martinez, Gabriela Chapa, Shirin Hasan, Tejabhiram Yadavalli, Dinesh Jaishankar, Deepak Shukla, Salvador Nares
MicroRNAs (miRNAs) are small, non-coding RNAs of ~18-25 nucleotides that have gained extensive attention as critical regulators in complex gene networks including immune cell lineage commitment, differentiation, maturation, and maintenance of immune homeostasis and function. Many viruses encode miRNAs that directly downregulate the expression of factors of the innate immune system, which includes proteins involved in promoting apoptosis and recruitment. In this study, we examined the expression profiles of three previously identified viral miRNAs (v-miRs) from the human herpesvirus (HHV) family, HSV-1 (miR-H1), KSHV (miR-K12-3-3p), and HCMV (miR-US4) in healthy and diseased periodontal tissues and observed increased levels of v-miRs in diseased tissues...
March 14, 2018: Biochimica et Biophysica Acta
Kai Zheng, Qiuying Liu, Shaoxiang Wang, Zhe Ren, Kaio Kitazato, Depo Yang, Yifei Wang
Herpes simplex virus 1 (HSV-1) encodes various microRNAs (miRNAs), whose targets are largely unknown. miR-H1 is the first discovered HSV-1 miRNA and is expressed predominantly in productive infection. Here we show that ubiquitin protein ligase E3 component n-recognin 1 (Ubr1) is a cellular target of miR-H1. Ubr1 is a RING-type E3 ubiquitin ligase of the Arg/N-end rule pathway, which causes the degradation of proteins bearing "destabilizing" N-terminal residues, such as neurodegeneration-associated protein fragment β-amyloid...
March 14, 2018: Virus Genes
Yiting Xie, Songlin He, Jinhua Wang
Herpes simplex virus type 1 (HSV-1) had led to kinds of clinical disorders and became an important cause of morbidity and mortality worldwide, such as herpetic gingivostomatitis in children. Previous studies reported that HSV-1 infection is common and has evolved a variety of mechanisms to evade the immune system, such as dysregulation of miRNAs. However, reports concerning the role of miRNA in HSV-1infection are limited. Here, we report that a host microRNA, miR-373, was significantly upregulated by HSV-1 infection in Hela cells and patients with herpetic gingivostomatitis and it facilitated HSV-1 replication in vitro...
January 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Maryam Ghanbari, Esmaeil Saberfar, Zahra Goodarzi, Hadi Lashini, Sahar Ghanbari, Mojtaba Karamimanesh, Kazem Baesi
Aim: Here, we use miR-122a that exhibits liver-specific expression for developing a post-transcriptional regulative system mediated by microRNAs. Background: Gene therapy with adenovirus (Ad) vectors that express herpes simplex virus thymidine kinase (HSVtk) and ganciclovir (GCV) have been suggested as a therapeutic strategy to cancer. However, Ad vectors injected into tumors are dispersed into the systemic circulation and transduce liver cells, resulting in severe hepatotoxicity...
2017: Gastroenterology and Hepatology From Bed to Bench
Lin Kuang, Yihui Deng, Xiaodan Liu, Zhixiang Zou, Lan Mi
MicroRNAs (miRNAs) are 22-nucleotide single-stranded RNAs which regulate gene expression by targeting 3' untranslated regions. Previous studies have suggested that miRNAs may be used as markers for investigating the molecular regulation of gene expression. In the present study, miRNA and mRNA expression profiles were investigated using a massively parallel next generation sequencing technique to compare herpes simplex virus (HSV)2-infected (n=3) and healthy (n=3) epithelial tissues from guinea pigs. Total RNA was isolated and RNA sequencing was performed using a HiSeq 2000 sequencing system...
September 2017: Experimental and Therapeutic Medicine
Gabriel Lutz, Igor Jurak, Eui Tae Kim, Ju Youn Kim, Michael Hackenberg, Andrew Leader, Michelle L Stoller, Donna M Fekete, Matthew D Weitzman, Donald M Coen, Angus C Wilson
Infection with herpes simplex virus-1 (HSV-1) brings numerous changes in cellular gene expression. Levels of most host mRNAs are reduced, limiting synthesis of host proteins, especially those involved in antiviral defenses. The impact of HSV-1 on host microRNAs (miRNAs), an extensive network of short non-coding RNAs that regulate mRNA stability/translation, remains largely unexplored. Here we show that transcription of the miR-183 cluster (miR-183, miR-96, and miR-182) is selectively induced by HSV-1 during productive infection of primary fibroblasts and neurons...
August 7, 2017: Viruses
Anna Majer, Kyle A Caligiuri, Kamilla K Gale, Yulian Niu, Clark S Phillipson, Timothy F Booth, Stephanie A Booth
Important roles of microRNAs (miRNAs) in regulating the host response during viral infection have begun to be defined. However, little is known about the functional roles of miRNAs within an in vivo acute viral encephalitis model. We therefore identified global changes in miRNA expression during acute herpes simplex virus type 1 (HSV-1) encephalitis (HSVE) in mice. We found that many of the highly upregulated miRNAs (miR-155, miR-146a and miR-15b) detected in HSV-1 infected brain tissue are known regulators of inflammation and innate immunity...
2017: PloS One
Xihan Li, Ying Huang, Yucheng Zhang, Na He
Reactivated varicella-zoster virus (VZV), which lies latent in the dorsal root ganglions and cranial nerves before its reactivation, is capable of causing herpes zoster (HZ), but the specific mechanism of virus reactivation and latency remains unknown. It was proposed that circulating microRNAs (miRNAs) in body fluids could potentially indicate infection. However, the connection between herpes zoster and circulating miRNAs has not been demonstrated. In this study, 41 HZ patients without superinfection were selected...
December 2, 2016: Viruses
Dongli Pan, Jean M Pesola, Gang Li, Seamus McCarron, Donald M Coen
Herpes simplex virus 1 (HSV-1) latency entails the repression of productive ("lytic") gene expression. An attractive hypothesis to explain some of this repression involves inhibition of the expression of ICP0, a lytic gene activator, by a viral microRNA, miR-H2, which is completely complementary to ICP0 mRNA. To test this hypothesis, we engineered mutations that disrupt miR-H2 without affecting ICP0 in HSV-1. The mutant virus exhibited drastically reduced expression of miR-H2 but showed wild-type levels of infectious virus production and no increase in ICP0 expression in lytically infected cells, which is consistent with the weak expression of miR-H2 relative to the level of ICP0 mRNA in that setting...
January 15, 2017: Journal of Virology
Yi Zhang, Jun Dai, Jinfeng Tang, Li Zhou, Mengzhou Zhou
Herpes simplex virus type 1 (HSV-1), a member of the Herpes viridae, is associated with a wide variety of nervous system diseases including meningitis and encephalitis. The data presented here demonstrate that miR-649 promotes the replication of HSV-1 without affecting cell viability. Further mechanistic studies revealed that MALT1 (mucosa associated lymphoid tissue lymphoma translocation gene 1) is directly targeted by miR-649. We then found that MALT1 and the downstream NF-κB signaling pathway, are involved in miR-649-induced HSV-1 replication...
June 2017: Journal of Medical Virology
Y Liu, H L Yang, F F Zhong, J Y Fan
BACKGROUND: The latency-associated transcript (LAT) gene of herpes simplex virus (HSV)-2 is the only detectable viral gene expressed during latent infection in neurons. LAT inhibits apoptosis and maintains latency by promoting the survival of infected neurons. However, whether LAT functions during HSV-2 infection via its encoded RNAs or via its encoded proteins remain unknown. Increasing evidence has indicated that LAT is likely to functionally promote the establishment of latent infection via LAT-encoded microRNAs (miRNAs)...
October 2016: Clinical and Experimental Dermatology
Diogo Piedade, José Miguel Azevedo-Pereira
MicroRNAs (miRNAs) are small non-coding RNAs important in gene regulation. They are able to regulate mRNA translation through base-pair complementarity. Cellular miRNAs have been involved in the regulation of nearly all cellular pathways, and their deregulation has been associated with several diseases such as cancer. Given the importance of microRNAs to cell homeostasis, it is no surprise that viruses have evolved to take advantage of this cellular pathway. Viruses have been reported to be able to encode and express functional viral microRNAs that target both viral and cellular transcripts...
June 2, 2016: Viruses
Priya Raja, Jennifer S Lee, Dongli Pan, Jean M Pesola, Donald M Coen, David M Knipe
UNLABELLED: Latent infections by viruses usually involve minimizing viral protein expression so that the host immune system cannot recognize the infected cell through the viral peptides presented on its cell surface. Herpes simplex virus (HSV), for example, is thought to express noncoding RNAs such as latency-associated transcripts (LATs) and microRNAs (miRNAs) as the only abundant viral gene products during latent infection. Here we describe analysis of HSV-1 mutant viruses, providing strong genetic evidence that HSV-infected cell protein 0 (ICP0) is expressed during establishment and/or maintenance of latent infection in murine sensory neurons in vivo Studies of an ICP0 nonsense mutant virus showed that ICP0 promotes heterochromatin and latent and lytic transcription, arguing that ICP0 is expressed and functional...
May 17, 2016: MBio
Zahid M Delwar, Guoyu Liu, Yvonne Kuo, Cleo Lee, Luke Bu, Paul S Rennie, William W Jia
Oncolytic herpes simplex virus type 1 (oHSV-1) therapy is an emerging treatment modality that selectively destroys cancer. Here we report use of a glioma specific HSV-1 amplicon virus (SU4-124 HSV-1) to selectively target tumour cells. To achieve transcriptional regulation of the SU4-124 HSV-1 virus, the promoter for the essential HSV-1 gene ICP4 was replaced with a tumour specific survivin promoter. Translational regulation was achieved by incorporating 5 copies of microRNA 124 target sequences into the 3'UTR of the ICP4 gene...
May 10, 2016: Oncotarget
K-X Zhang, Y Matsui, C Lee, O Osamu, L Skinner, J Wang, A So, P S Rennie, W W Jia
Urothelial bladder cancer is the most common malignancy of the urinary tract. Although most cases are initially diagnosed as non-muscle-invasive, more than 80% of patients will develop recurrent or metastatic tumors. No effective therapy exists currently for late-stage metastatic tumors. By intravesical application, local administration of oncolytic Herpes Simplex virus (oHSV-1) can provide a promising new therapy for this disease. However, its inherent neurotoxicity has been a perceived limitation for such application...
2016: Gene Therapy
Zhiyuan Han, Xianjie Liu, Xiaoqing Chen, Xusha Zhou, Te Du, Bernard Roizman, Guoying Zhou
We report on the properties and function of two herpes simplex virus-1 (HSV-1) microRNAs (miRNAs) designated "miR-H28" and "miR-H29." Both miRNAs accumulate late in productive infection at a time when, for the most part, viral DNA and proteins have been made. Ectopic expression of miRNA mimics in human cells before infection reduced the accumulation of viral mRNAs and proteins, reduced plaque sizes, and at vey low multiplicities of infection reduced viral yields. The specificity of the miRNA mimics was tested in two ways...
February 16, 2016: Proceedings of the National Academy of Sciences of the United States of America
Guo-Qing Wu, Xiao Wang, Hong-Ying Zhou, Ke-Qun Chai, Qian Xue, Ai-Hong Zheng, Xiu-Ming Zhu, Jian-Yong Xiao, Xu-Hua Ying, Fu-Wei Wang, Tao Rui, Li-Yun Xu, Yong-Kui Zhang, Yi-Ji Liao, Dan Xie, Li-Qin Lu, Dong-Sheng Huang
The dual-luciferase reporter assay is widely used for microRNA target identification and the functional validation of predicted targets. To determine whether curcumin regulates expression of the histone methyltransferase enhancer of zeste homolog 2 (EZH2) by targeting its 3'untranslated region (3'UTR), two luciferase reporter systems containing exactly the same sequence of the EZH2 3'UTR were used to perform dual-luciferase reporter assays. Surprisingly, there were certain discrepancies between the luciferase activities derived from these two reporter constructs...
December 1, 2015: Scientific Reports
Yusha Ru, Yan Zhang, Shaozhen Zhao
MicroRNAs (miRNAs) are a class of small (21-2i nucleotictes), single-stranded, noncoding RNA molecules that regulate gene expression at the post-transcriptional or translational level by binding to the 3'-untranslated region of the target mRNAs. miRNAs ubiquitously exist in the genome of an organism. More than two hundred miRNA species are expressed in the eye, of which 25% are found in the cornea. miRNAs play important roles in corneal development, differentiation, glycogen metabolism, post-injury regeneration, and maintenance of homeostasis...
March 2015: [Zhonghua Yan Ke za Zhi] Chinese Journal of Ophthalmology
Huiliang Zhao, Chunying Zhang, Guangjun Hou, Jijun Song
Herpes simplex virus 1 (HSV-1) microRNAs (miRNAs) mostly located in transcription-associated transcript (LAT) region have been identified that play critical roles in the intricate host-pathogen interaction networks. Increasing evidences throw new insight into the role of miRNA-mediated miRNA-mRNA cross-talk in HSV-1 latent or acute infection. In the present study, we found that hsv-1 miR-H4-5p (here termed as miR-H4b) can down-regulate the expression of cyclin-dependent kinase inhibitor 2A (CDKN2A, p16) in neuroblastoma (SHSY5Y) cell lines...
2015: International Journal of Clinical and Experimental Medicine
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