Marek's disease virus (MDV) is a highly cell-associated alphaherpesvirus that causes deadly lymphomas in chickens. While vaccination protects against clinical symptoms, MDV field strains can still circulate in vaccinated flocks and continuously evolve towards greater virulence. MDV vaccines do not provide sterilizing immunity, allowing the virus to overcome vaccine protection, and has increased the need for more potent vaccines or alternative interventions. In this study, we addressed if the CRISPR/Cas9 system can protect cells from MDV replication. We first screened a number of guide RNAs (gRNAs) targeting essential MDV genes for their ability to prevent virus replication. Single gRNAs significantly inhibited virus replication, but could result in the emergence of escape mutants. Strikingly, combining two or more gRNAs completely abrogated virus replication and no escape mutants were observed upon serial passaging. Our study provides the first proof-of-concept, demonstrating that the CRISPR/Cas9 system can be efficiently used to block MDV replication. The presented findings lay the foundation for future research to completely protect chickens from this deadly pathogen.
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http://dx.doi.org/10.1038/s41598-020-67951-1 | DOI Listing |
J Med Virol
December 2024
Division of Microbiology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, Japan.
Placental trophoblasts constitute the interface between the fetal and maternal environments and physically prevent maternal-fetal viral transmission. However, congenital human cytomegalovirus (HCMV) infection in the early stages of pregnancy results in severe symptoms in the fetus. HCMV is the most common causative agent of intrauterine infection.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Introduction: To analyze the molecular pathogenesis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a small animal model such as mice is needed: human angiotensin converting enzyme 2 (hACE2), the receptor of SARS-CoV-2, needs to be expressed in the respiratory tract of mice.
Methods: We conferred SARS-CoV-2 susceptibility in mice by using an adenoviral vector expressing hACE2 driven by an elongation factor 1α (EF1α) promoter with a leftward orientation.
Results: In this model, severe pneumonia like human COVID-19 was observed in SARS-CoV-2-infected mice, which was confirmed by dramatic infiltration of inflammatory cells in the lung with efficient viral replication.
Virus Evol
November 2024
Department of Paraclinical Sciences, Norwegian University of Life Sciences, Post box 5003, Ås 1432, Norway.
Over a decade since its discovery, piscine myocarditis virus (PMCV) remains a significant pathogen in Atlantic salmon aquaculture. Despite this significant impact, the genomic landscape, evolutionary dynamics, and virulence factors of PMCV are poorly understood. This study enhances the existing PMCV sequence dataset by adding 34 genome sequences and 202 new ORF3 sequences from clinical cardiomyopathy syndrome (CMS) cases in Norwegian aquaculture.
View Article and Find Full Text PDFFront Cell Infect Microbiol
December 2024
Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
In the context of chronic hepatitis B virus (HBV) infection, the continuous replication of HBV within host hepatocytes is a characteristic feature. Rather than directly causing hepatocyte destruction, this replication leads to immune dysfunction and establishes a state of T-B immune tolerance. Successful clearance of the HBV virus is dependent on the close collaboration between humoral and cellular immunity.
View Article and Find Full Text PDFAdv Biomed Res
November 2024
Department of Basic Sciences, School of Medicine, Bam University of Medical Sciences, Bam, Iran.
The growth of nanoscale sciences enables us to define and design new methods and materials for a better life. Health and disease prevention are the main issues in the human lifespan. Some nanoparticles (NPs) have antimicrobial properties that make them useful in many applications.
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