Marek's Disease Virus Cluster 3 miRNAs Restrict Virus' Early Cytolytic Replication and Pathogenesis

Herpesvirus-encoded microRNAs (miRNAs) have been discovered in infected cells; however, lack of a suitable animal model has hampered functional analyses of viral miRNAs in vivo. Marek's disease virus (MDV) ( 2, GaHV-2) genome contains 14 miRNA precursors, which encode 26 mature miRNAs, grouped...

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Bibliographic Details
Published in:Viruses 2020-11, Vol.12 (11), p.1317
Main Authors: Liao, Yifei, Zhuang, Guoqing, Sun, Aijun, Khan, Owais A, Lupiani, Blanca, Reddy, Sanjay M
Format: Article
Language:English
Subjects:
Animal models
Animals
Artificial chromosomes
Atrophy
Cell culture
Cell size
Cells, Cultured
Chickens - virology
Cloning
Deoxyribonucleic acid
DNA
Fibroblasts
Fibroblasts - pathology
Fibroblasts - virology
Gene Deletion
Gene expression
Genomes
Herpesvirus 2, Gallid - genetics
Herpesvirus 2, Gallid - pathogenicity
Herpesvirus 2, Gallid - physiology
Infections
Laboratories
Lymphocytes
lymphoid organ atrophy
Marek Disease - virology
Marek's disease
Marek’s disease virus
MicroRNAs
MicroRNAs - genetics
miRNA
Monoclonal antibodies
Pathogenesis
Peripheral blood
Phenotypes
Poultry
Replication
RNA, Viral - genetics
Specific Pathogen-Free Organisms
Tumors
Virulence
Virus Replication - genetics
Viruses
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Summary:Herpesvirus-encoded microRNAs (miRNAs) have been discovered in infected cells; however, lack of a suitable animal model has hampered functional analyses of viral miRNAs in vivo. Marek's disease virus (MDV) ( 2, GaHV-2) genome contains 14 miRNA precursors, which encode 26 mature miRNAs, grouped into three clusters. In this study, the role of MDV-encoded cluster 3 miRNAs, also known as mdv1-miR-M8-M10, in pathogenesis was evaluated in chickens, the natural host of MDV. Our results show that deletion of cluster 3 miRNAs did not affect virus replication and plaque size in cell culture, but increased early cytolytic replication of MDV in chickens. We also observed that deletion of cluster 3 miRNAs resulted in significantly higher virus reactivation from peripheral blood lymphocytes. In addition, pathogenesis studies showed that deletion of cluster 3 miRNAs resulted in more severe atrophy of lymphoid organs and reduced mean death time, but did not affect the incidence of MDV-associated visceral tumors. We confirmed these results by generating a cluster 3 miRNA revertant virus in which the parental MDV phenotype was restored. To the best of our knowledge, our study provides the first evidence that MDV cluster 3 miRNAs play an important role in modulating MDV pathogenesis.
ISSN:1999-4915
1999-4915
DOI:10.3390/v12111317