CRISPR-cas technology and use in antiviral development DOI Open Access
Zeynep Yolhan Şeflek, Mustafa Hasöksüz

Journal of Istanbul Veterinary Sciences, Journal Year: 2024, Volume and Issue: 8(2), P. 195 - 206

Published: Aug. 31, 2024

Throughout history, viral diseases have periodically reached pandemic proportions and had devastating effects on human history. With the advancement of science technology, antivirals been developed continue to be in fight against diseases. The difficulty development antirival has tried use new technologies antiviral. One these is CRISPR/Cas system. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) defines a series DNA sequences called clusters regularly interspaced palindromic repeats, CAS endonucleases that as guide recognize cut specific chains related region. While protein engineering systems defined before can off-target cause undesirable results, system reduces this risk by Watson-Crick base pairing. In infections humans animals, vaccine protection methods are widely used due problems developing antivirals. On other hand, vaccination, inadequacies long-term immunity emergence or epidemics mutational changes viruses pave way for This article emphasizes history working areas CRISPR-Cas technology potential applications method antiviral animal

Language: Английский

Emerging Hypervirulent Marek’s Disease Virus Variants Significantly Overcome Protection Conferred by Commercial Vaccines DOI Creative Commons
Jinling Liu, Man Teng, Luping Zheng

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(7), P. 1434 - 1434

Published: June 25, 2023

As one of the most important avian immunosuppressive and neoplastic diseases, Marek's disease (MD), caused by oncogenic virus (MDV), has huge economic losses worldwide over past five decades. In recent years, MD outbreaks have occurred frequently in MD-vaccinated chicken flocks, but key pathogenic determinants influencing factors remain unclear. Herein, we analyzed pathogenicity seven newly isolated MDV strains from tumor-bearing chickens China found that all them were to hosts, among which four isolates, SDCW01, HNXZ05, HNSQ05 HNSQ01, considered be hypervirulent (HV-MDV) strains. At 73 days infection experiment, cumulative incidences 100%, 93.3%, 90% with mortalities 83.3%, 73.3%, 60% 86.7%, respectively, for viruses. The gross occurrences tumors 50%, 33.3%, 30% 63.3%, accompanied significant hepatosplenomegaly serious atrophy immune organs. Furthermore, protection effects commercial vaccines against CVI988, HVT, CVI988+HVT, 814 explored. Unexpectedly, during 67 post-virus challenge, indices (PIs) these only 46.2%, 38.5%, 28%, birds received monovalent CVI988 or HVT still developed 7.7% 11.5%, respectively. To our knowledge, this is first demonstration simultaneous comparison efficacy multiple different vaccine Our study revealed HV-MDV variants circulating could significantly break through classical currently widely used. For future work, there an urgent need develop novel, more effective tackling new challenge emerging sustainable control MD.

Language: Английский

Citations

13
Immune escape of avian oncogenic Marek’s disease herpesvirus and antagonistic host immune responses DOI Creative Commons
Zhi-Jian Zhu, Man Teng, Yu Liu

et al.

npj Vaccines, Journal Year: 2024, Volume and Issue: 9(1)

Published: June 15, 2024

Marek's disease virus (MDV) is a highly pathogenic and oncogenic alpha herpesvirus that causes (MD), which one of the most important immunosuppressive rapid-onset neoplastic diseases in poultry. The onset MD lymphomas other clinical can be efficiently prevented by vaccination; these vaccines are heralded as first demonstration successful vaccination strategy against cancer. However, persistent evolution epidemic MDV strains towards greater virulence has recently resulted frequent outbreaks vaccinated chicken flocks worldwide. Herein, we provide an overall review focusing on discovery identification strategies evades host immunity attacks immune system. We have also highlighted decrease efficacy current vaccines. prospects, new techniques for development efficient vaccines, together with possibilities antiviral therapy MD, discussed.

Language: Английский

Citations

5
Roles of circRNAs in viral pathogenesis DOI Creative Commons
Jiayin Liu, Yiming Wang,

Meichun Zheng

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2025, Volume and Issue: 15

Published: March 13, 2025

Circular RNAs (circRNAs) are a class of non-coding with covalently closed circular structure, lacking 5’-caps or 3’-poly(A) tails. They relatively conserved, highly stable, and often exhibit tissue- cell-specific production in eukaryotic cells. Based on the advances sequencing technologies bioinformatics, multiple reports have suggested that viruses other microorganisms may encode circRNA-like molecules, providing new insights into physiological pathological roles circRNAs. The innate immune system functions as body’s primary defense mechanism against viral infections. It detects pathogen-associated molecular patterns (PAMPs) activates signaling pathways to suppress replication limit their spread. CircRNAs involved regulation host play essential pathogenesis. has been shown circRNAs can regulate gene expression by acting miRNA sponges protein sponges, encoding small proteins specific cases. For example, previous studies revealed participate antiviral response through competitive endogenous RNA (ceRNA) network sponges. This review highlights research progress host- virus-encoded host-virus interactions, well potential diagnostic biomarkers therapeutic targets clinical applications.

Language: Английский

Citations

0
Cell wall remodeling promotes callus formation in poplar DOI Creative Commons
Geng Zhang, Peipei Liu, Guifang Zhang

et al.

Molecular Horticulture, Journal Year: 2024, Volume and Issue: 4(1)

Published: April 30, 2024

Language: Английский

Citations

3
Novel lncRNA 803 related to Marek’s disease inhibits apoptosis of DF-1 cells DOI

Shuo Han,

Shuang Zhao,

Haile Ren

et al.

Avian Pathology, Journal Year: 2024, Volume and Issue: 53(4), P. 229 - 241

Published: Feb. 7, 2024

Marek's disease (MD) is a neoplastic that significantly affects the poultry industry. Long non-coding RNAs (lncRNAs) are crucial regulatory factors in various biological processes, including tumourigenesis. However, involvement of novel lncRNAs course MD virus (MDV) infection still underexplored. Here, we present first comprehensive characterization differentially expressed chicken spleen at different stages MDV infection. A series was identified each stage through screening. Notably, our investigation revealed lncRNA, lncRNA 803, which exhibited significant differential expression and likely to be associated with p53 pathway. Further analyses demonstrated overexpression 803 positively regulated TP53BP1 DF-1 cells, leading inhibition apoptosis. This study focus on profiles spleens during pathogenesis. Our findings highlight potential role p53-related pathogenesis provide valuable insights for decoding molecular mechanism involving RNA.

Language: Английский

Citations

2
Circ1811 suppresses gastric cancer progression by regulating the miR-632/DAPK1 axis DOI Creative Commons
Min Fu, Jianmei Gu,

Dan Yu

et al.

Gene, Journal Year: 2024, Volume and Issue: 910, P. 148331 - 148331

Published: March 3, 2024

Compelling evidence has identified circRNAs as crucial regulators in initiation and progression of various cancers, including gastric cancer (GC). However, the function regulatory mechanisms GC remain largely unknown. In this study, attention is paid to a novel circular RNA circ1811, which exerts significant downregulated expression tissues compared with adjacent non-cancerous tissues. The circ1811 tumor negatively correlated extent lymphatic metastasis patients. Overexpression inhibited cell proliferation, migration invasion while promoting apoptosis, whereas knockdown led opposite effects. AGO2 RIP dual luciferase reporter assays indicated that directly sponges miR-632 upregulate DAPK1. Collectively, acts tumor-suppressor for by regulating miR-632/DAPK1 axis. Our findings suggest potential ideal biomarker therapeutic target GC.

Language: Английский

Citations

2
Effect of Pre-Treatment with a Recombinant Chicken Interleukin-17A on Vaccine Induced Immunity against a Very Virulent Marek’s Disease Virus DOI Creative Commons
Nitish Boodhoo, Ayumi Matsuyama-Kato,

Sugandha Raj

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(8), P. 1633 - 1633

Published: July 27, 2023

The host response to pathogenic microbes can lead expression of interleukin (IL)-17, which has antimicrobial and anti-viral activity. However, relatively little is known about the basic biological role chicken IL-17A against avian viruses, particularly Marek’s disease virus (MDV). We demonstrate that, following MDV infection, upregulation mRNA an increase in frequency IL-17A+ T cells spleen occur compared control chickens. To elaborate on chIL-17A MD, full-length coding sequence was cloned into a pCDNA3.1-V5/HIS TOPO plasmid. effect treatment with pcDNA:chIL-17A plasmid combination vaccine (HVT) very virulent(vv)MDV challenge or vvMDV infection assessed. In HVT vaccination, chickens that were inoculated had reduced tumor incidence received empty vector vaccinated only (66.6% + group 73.33% versus 53.3% pcDNA:chIL-17A). Further analysis demonstrated and/or expressing lower MDV-Meq transcripts spleen. conclusion, influence immunity conferred by vaccination

Language: Английский

Citations

4
Duck Plague Virus-encoded MicroRNA Dev-miR-D28-3p Inhibits Viral Replication via Targeting UL27 DOI

Hui Ni,

Xingcui Zhang, Juan Huang

et al.

Veterinary Microbiology, Journal Year: 2024, Volume and Issue: 297, P. 110202 - 110202

Published: July 29, 2024

Language: Английский

Citations

1
MDV-encoded protein kinase US3 phosphorylates WTAP to inhibit transcriptomic m6A modification and cellular protein translation DOI

Lele Wang,

Zhu Wenhui,

Lele Gong

et al.

Veterinary Microbiology, Journal Year: 2024, Volume and Issue: 300, P. 110335 - 110335

Published: Dec. 4, 2024

Citations

1
Efficient Cross-Screening and Characterization of Monoclonal Antibodies against Marek’s Disease Specific Meq Oncoprotein Using CRISPR/Cas9-Gene-Edited Viruses DOI Creative Commons
Man Teng, Jinling Liu, Qin Luo

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(4), P. 817 - 817

Published: March 23, 2023

Marek’s disease (MD) caused by pathogenic virus type 1 (MDV−1) is one of the most important neoplastic diseases poultry. MDV−1-encoded unique Meq protein major oncoprotein and availability Meq-specific monoclonal antibodies (mAbs) crucial for revealing MDV pathogenesis/oncogenesis. Using synthesized polypeptides from conserved hydrophilic regions as immunogens, together with hybridoma technology primary screening cross immunofluorescence assay (IFA) on Meq-deleted MDV−1 viruses generated CRISPR/Cas9-gene editing, a total five positive hybridomas were generated. Four these hybridomas, namely 2A9, 5A7, 7F9 8G11, further confirmed to secrete specific against IFA staining 293T cells overexpressing Meq. Confocal microscopic analysis stained nuclear localization in MDV-infected CEF MDV-transformed MSB-1 cells. Furthermore, two mAb clones, 2A9-B12 8G11-B2 derived 2A9 respectively, displayed high specificity proteins strains diverse virulence. Our data presented here, using polypeptide immunization combined CRISPR/Cas9 gene-edited viruses, has provided new efficient approach future generation mAbs viral proteins.

Language: Английский

Citations

3