TRIM52 inhibits Japanese Encephalitis Virus replication by degrading the viral NS2A

Fan, Wenchun; Qian, Suhong; Zhou, Yun; Chen, Huanchun; Li, Xiangmin; Qian, Ping

doi:10.1038/srep33698

Cited by 60 publications

(48 citation statements)

References 43 publications

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“…A recent study showed that the E3-ubiquitin ligase TRIM52, which belongs to the TRIM family of proteins, regulates JEV infection by directly interacting with NS2A of JEV and leading to NS2A degradation40. Whether Nedd4 can directly interact with JEV nonstructural proteins to affect autophagy activity and virus infection, and if these molecules and pathways are also exploited for replication by the emerging infectious neurotropic Flaviviruses , such as Zika virus and West Nile virus (WNV), remain interesting avenues to be explored in future studies.…”

Section: Discussionmentioning

confidence: 99%

E3 Ubiquitin Ligase Nedd4 Promotes Japanese Encephalitis Virus Replication by Suppressing Autophagy in Human Neuroblastoma Cells

Zhu

Chen

et al. 2017

Sci Rep

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Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes the most prevalent viral encephalitis in Asia. Since JEV is a neurotropic virus, it is important to identify key molecules that mediate JEV infection in neuronal cells and to investigate their underlying mechanisms. In this study, the critical role of Nedd4, an E3 ubiquitin ligase that is highly expressed in the central nervous system, was examined in JEV propagation. In SK-N-SH neuroblastoma cells, Nedd4 was up-regulated in response to JEV infection. Moreover, down-regulation of Nedd4 resulted in a significant decrease in JEV replication without alterations in virus attachment and internalization or in JEV pseudotyped virus infection, suggesting that Nedd4 participates in the replication but not in the entry stage of JEV infection. Further functional analysis showed that Nedd4 attenuated JEV-induced autophagy, which negatively regulates virus replication during infection. These results suggest that Nedd4 facilitates the replication of JEV by suppressing virus-induced autophagy. Taken together, our results indicate that Nedd4 plays a crucial role in JEV infection of neuronal cells, which provides a potential target for the development of novel treatment to combat JEV infection.

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Section: Discussionmentioning

confidence: 99%

E3 Ubiquitin Ligase Nedd4 Promotes Japanese Encephalitis Virus Replication by Suppressing Autophagy in Human Neuroblastoma Cells

Zhu

Chen

et al. 2017

Sci Rep

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“…Song, et al Veterinary Microbiology 239 (2019) 108498 budding and release of influenza virus . TRIM family proteins also interfere at multiple stages of the viral life cycle, including degrading viral proteins (Fan et al, 2016), decreasing gene expression and impeding viral assembly (Barr et al, 2008;Wu et al, 2006); however, as an immunosuppressive virus, PRRSV can negatively regulate the host immune response to promote viral propagation via several pathways, including multiple interferon-pathway suppression (Kim et al, 2010;Beura et al, 2010;Li et al, 2010), host antiviral protein degradation (Huang et al, 2016(Huang et al, , 2014, disturbance of monocyte/ macrophages, B cell, and T cell development (Huang et al, 2015;Loving et al, 2015;Fan et al, 2015), and reduced expression of antigen presenting molecules (Chen et al, 2018). In the present study, we found that HP-PRRSV infection promoted S100A9 expression in both PAMs and Marc-145 cells.…”

Section: Discussionmentioning

confidence: 99%

S100A9 regulates porcine reproductive and respiratory syndrome virus replication by interacting with the viral nucleocapsid protein

Song

Bai

Liu

et al. 2019

Veterinary Microbiology

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Porcine reproductive and respiratory syndrome virus (PRRSV) has caused huge economic losses to the pig industry worldwide over the last 30 years, yet the associated viral-host interactions remain poorly understood. S100A9 is a damage-associated molecular pattern of the S100 protein family. Here, we found that PRRSV infection stimulated S100A9 expression in porcine alveolar macrophages (PAMs) and Marc-145 cells. S100A9 inhibited PRRSV replication via cellular Ca 2+ dependent manner. The viral nucleocapsid (N) protein co-localized with S100A9 in the cytoplasm, and directly interacted at amino acid 78 of S100A9 and amino acids 36-37 of N protein. Moreover, we also found that the mutant S100A9 (E78Q) protein exhibited decreased antiviral activity against PRRSV compared with the parent S100A9. Recombinant PRRSV rBB (36/37) with two mutations in amino acid 36-37 in the N protein exhibited greater replication than the parent PRRSV BB0907 in S100A9overexpressed PAM and Marc-145 cells. Thus, S100A9 may restrict PRRSV proliferation by interacting with the viral N protein.

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“…JEV infects a variety of cell types from diverse species (including mammals, birds, amphibians, and insects), suggesting that JEV can likely access multiple cell types using multiple host receptors 14 . In recent years, tremendous progress has been made in understanding the viral components required for the various steps of JEV entry and replication, but little is known about the host cell components involved in this process [15][16][17][18] .…”

Section: Introductionmentioning

confidence: 99%

CRISPR screening of porcine sgRNA library identified host factors essential for Japanese encephalitis virus replication

Zhao

Liu

Xiao

et al. 2019

Preprint

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Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic flavivirus that causes encephalitis and reproductive disorders in mammalian species. However, key host genes involved in the JEV life cycle and cell death are poorly understood. Here, we designed 85,674 single guide RNAs (sgRNAs) targeting 17,743 protein-coding genes, 11,053 long ncRNAs (lncRNAs), and 551 microRNAs (miRNAs) in the porcine genome, and subsequently developed a porcine sgRNA library and genome-scale CRISPR/Cas9 knockout (PigGeCKO) system. These sgRNAs were delivered into porcine kidney-15 (PK-15) cells that constitutively express Cas9, positive selection screening of the resulting PigGeCKO cell collection for resistance to JEV-induced cell death led to the identification of several previously unreported genes required for JEV infection. We conducted follow-up studies to verify the dependency of JEV on these genes, and identified functional contributions for six of the many candidate JEV-related host genes, including an endoplasmic reticulum membrane protein complex subunit 3 (EMC3) and calreticulin (CALR). Additionally, we identified that four genes associated with heparan sulfate proteoglycans (HSPGs) metabolism, specifically those responsible for HSPG sulfurylation, facilitated JEV entry into PK-15 cells. Thus, beyond our development of the largest CRISPR-based functional genomic screening platform for pig research to date, this work deepens our basic understanding of flavivirus infection and identifies multiple potentially vulnerable targets for the development of medical and breeding technologies to prevent and treat diseases caused by Japanese encephalitis virus.

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TRIM52 inhibits Japanese Encephalitis Virus replication by degrading the viral NS2A

Cited by 60 publications

References 43 publications

E3 Ubiquitin Ligase Nedd4 Promotes Japanese Encephalitis Virus Replication by Suppressing Autophagy in Human Neuroblastoma Cells

E3 Ubiquitin Ligase Nedd4 Promotes Japanese Encephalitis Virus Replication by Suppressing Autophagy in Human Neuroblastoma Cells

S100A9 regulates porcine reproductive and respiratory syndrome virus replication by interacting with the viral nucleocapsid protein

CRISPR screening of porcine sgRNA library identified host factors essential for Japanese encephalitis virus replication

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