Project description:Varicella Zoster Virus (VZV) is a skin-tropic virus that infects epidermal keratinocytes and causes chickenpox. Although common, VZV infection can be life-threatening particularly in the immunocompromised. Therefore, understanding VZV-keratinocyte interactions is important to find new treatments beyond vaccination and anti-viral drugs. In VZV- infected skin, Kallikrein 6 (KLK6), and the ubiquitin-ligase MDM2 are up-regulated concomitant with Keratin 10 (K10) down-regulation. MDM2 binds to K10 targeting it for degradation via the ubiquitin-proteasome pathway. Preventing K10 degradation reduced VZV propagation in culture and prevented epidermal disruption in skin explants. K10 knockdown induced expression of the nuclear receptor subfamily 4, group A, member 1 (NR4A1) and enhanced viral propagation in culture. NR4A1 knockdown prevented viral propagation in culture, reduced LC3 levels and increased LAMP2 expression. We therefore describe a novel drug-able pathway whereby MDM2 ubiquitinates and degrades K10 increasing NR4A1 expression allowing VZV replication and propagation.
Project description:Varicella pneumonia is the most common and severe complication of primary varicella-zoster virus (VZV) infection in adults. Pathogenesis of varicella pneumonia is largely unknown, mainly due to limited availability of clinical specimens and lack of appropriate VZV animal models. Simian varicella virus (SVV) infection of nonhuman primates closely recapitulates clinical and pathogenic features of human VZV disease. This study aimed to elucidate the virus and host factors that contribute to the pathogenesis of varicella pneumonia. The deposited data present changes in gene expression in the lung of SVV-infected cynomolgus macaques (Macaca fascicularis) at 3, 6 and 9 days after infection, and mock-infected control macaques at 3 days after infection.
Project description:The alpha-herpesvirus Varicella-Zoster Virus (VZV), the causative agent of chicken pox, infects most humans worldwide and remains latent in peripheral neuronal cells for life. Its reactivation triggers herpes zoster and sporadic disseminated infection, in particular in the central nervous system (CNS) where it is associated with severe pathologies. VZV replication is efficiently controlled with antivirals, however the emergence of treatment-resistant VZV variants constitutes an increasing healthcare issue, calling for in-depth analysis of molecular VZV-host interactions to foster general knowledge and promote identification of novel therapeutic targets. Here we conducted a mass spectrometry-based survey in neuronal SK-N-BE2 cells, combining proteome analysis of VZV-infected cells with systematic characterization of VZV proteins’ functions through identifying their individual host partners and effects on the host proteome. In this dataset, we systematically assessed proteome changes elicited by the expression of individual viral proteins – the so called “effectome”, which allowed us to gain unprecedented insights in the activity of individual VZV ORFs.
Project description:The alpha-herpesvirus Varicella-Zoster Virus (VZV), the causative agent of chicken pox, infects most humans worldwide and remains latent in peripheral neuronal cells for life. Its reactivation triggers herpes zoster and sporadic disseminated infection, in particular in the central nervous system (CNS) where it is associated with severe pathologies. VZV replication is efficiently controlled with antivirals, however the emergence of treatment-resistant VZV variants constitutes an increasing healthcare issue, calling for in-depth analysis of molecular VZV-host interactions to foster general knowledge and promote identification of novel therapeutic targets. Here we conducted a mass spectrometry-based survey in neuronal SK-N-BE2 cells, combining proteome analysis of VZV-infected cells with systematic characterization of VZV proteins’ functions through identifying their individual host partners and effects on the host proteome. To generate this specific dataset, we used AP-MS and a Bayesian modelling approach to characterize the VZV-host interactome. We collectively identified 1184 interactions between 56 viral and 900 human proteins.
Project description:In this study, we screened the differentially expressed genes (DEGs) in SH-SY5Y cells with Varicella-Zoster Virus-Infected using RNAseq technique to explore the molecular mechanisms of Herpes zoster pain
Project description:Varicella-zoster virus (VZV), an alphaherpesvirus, causes chickenpox (varicella) in young children with an annual minimum of 140 million new cases and herpes zoster in senior, a painful and debilitating disease with 3-5‰ incidence. A complex structural transcriptome of VZV, which numerous novel transcripts, transcript isoforms, and unknown splice events are found during cell infection. Circular RNA (circRNA), a newly important component of the transcriptome, is increasing discoveries of circRNA function in mammalian cells. However, VZV encoded circRNA remains unexplored. The code used in this study and extended data are available from the GitHub repository (https://github.com/ShaominYang/VZV_circRNA)
Project description:The alpha-herpesvirus Varicella-Zoster Virus (VZV), the causative agent of chicken pox, infects most humans worldwide and remains latent in peripheral neuronal cells for life. Its reactivation triggers herpes zoster and sporadic disseminated infection, in particular in the central nervous system (CNS) where it is associated with severe pathologies. VZV replication is efficiently controlled with antivirals, however the emergence of treatment-resistant VZV variants constitutes an increasing healthcare issue, calling for in-depth analysis of molecular VZV-host interactions to foster general knowledge and promote identification of novel therapeutic targets. Here we conducted a mass spectrometry-based survey in neuronal SK-N-BE2 cells, combining proteome analysis of VZV-infected cells with systematic characterization of VZV proteins’ functions through identifying their individual host partners and effects on the host proteome. We identified host proteins and signalling routes involved in VZV-mediated cell cycle progression, blockade of apoptosis, alteration of neuronal differentiation and innate immunity evasion. We functionally evaluated the 116 most prominent host proteins by loss-of-function assay and unveiled yet uncharacterized dependency and restriction factors. We generated stable knockout BFP positive SK-N-BE2 cells to validate their function in VZV replication assays as compared to Non-Targeting-Control (NTC) cells.