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Article

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

Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Current address: College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, China.
§
Current address: Texas A&M Veterinary Medical Diagnostic Laboratory, Texas A&M University, Canyon, TX 79016, USA.
Viruses 2020, 12(11), 1317; https://doi.org/10.3390/v12111317
Received: 28 October 2020 / Revised: 12 November 2020 / Accepted: 13 November 2020 / Published: 17 November 2020
(This article belongs to the Special Issue Animal Herpesviruses Pathogenesis and Immunity)
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) (Gallid alphaherpesvirus 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. View Full-Text
Keywords: Marek’s disease virus; miRNA; replication; lymphoid organ atrophy; pathogenesis Marek’s disease virus; miRNA; replication; lymphoid organ atrophy; pathogenesis
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MDPI and ACS Style

Liao, Y.; Zhuang, G.; Sun, A.; Khan, O.A.; Lupiani, B.; Reddy, S.M. Marek’s Disease Virus Cluster 3 miRNAs Restrict Virus’ Early Cytolytic Replication and Pathogenesis. Viruses 2020, 12, 1317. https://doi.org/10.3390/v12111317

AMA Style

Liao Y, Zhuang G, Sun A, Khan OA, Lupiani B, Reddy SM. Marek’s Disease Virus Cluster 3 miRNAs Restrict Virus’ Early Cytolytic Replication and Pathogenesis. Viruses. 2020; 12(11):1317. https://doi.org/10.3390/v12111317

Chicago/Turabian Style

Liao, Yifei, Guoqing Zhuang, Aijun Sun, Owais A. Khan, Blanca Lupiani, and Sanjay M. Reddy. 2020. "Marek’s Disease Virus Cluster 3 miRNAs Restrict Virus’ Early Cytolytic Replication and Pathogenesis" Viruses 12, no. 11: 1317. https://doi.org/10.3390/v12111317

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