establishment-evaluation-an-vitro-human-based-advanced-model

Establishment and Evaluation of an <em>In Vitro</em> Human-Based Advanced Model of Pulmonary Fibrosis

Pulmonary fibrosis is characterized by irreversible destruction of alveolar structure and excessive deposition of extracellular matrix. Although animal ...

Guangzhou Medical University

To replicate, spread and persist in the host environment, viruses have evolved several immunological escape mechanisms via the action of specific viral proteins. The model "host shut off" adopted by virion host shut off (VHS) protein of Herpes simplex type 1 (HSV-1) represents an immune evasion mechanism which affects the best-characterized component of the innate immunological response, protein kinase R (PKR). However, up to now, the real mechanism employed by VHS to control PKR is still unknown. In this paper, we implement and extend our previous findings reporting that wild-type HSV-1 is able to control PKR, whereas a VHS mutant virus (R2621) clearly induces an accumulation of phosphorylated PKR in several cell types in a VHS-RNase activity-dependent manner. Furthermore, we demonstrate for the first time a new PKR-regulatory mechanism based on the involvement of Us3 and UL13 tegument viral proteins. The combined approach of transfection and infection assay was useful to discover the new role of both viral proteins in the immunological escape and demonstrate that Us3 and UL13 control the accumulation of the phosphorylated form (ph-PKR). Lastly, since protein kinases are tightly regulated by phosphorylation events and, at the same time, phosphorylate other proteins by inducing post-translational modifications, the interplay between Us3 and VHS during HSV-1 infection has been investigated. Interestingly, we found that VHS protein accumulates at higher molecular weight following Us3 transfection, suggesting an Us3-mediated phosphorylation of VHS. These findings reveal a new intriguing interplay between viral proteins during HSV-1 infection involved in the regulation of the PKR-mediated immune response.

Article	Year
VHS, US3 and UL13 viral tegument proteins are required for Herpes Simplex Virus-Induced modification of protein kinase R. Scientific reports\| PubMed ID: 32221365	2020
Author Correction: VHS, US3 and UL13 viral tegument proteins are required for Herpes Simplex Virus-Induced modification of protein kinase R. Scientific reports\| PubMed ID: 33785828	2021

Zhixiang Lei

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