Protein 2B of Coxsackievirus B3 Induces Autophagy Relying on Its Transmembrane Hydrophobic Sequences

Wu, Heng; Zhai, Xia; Chen, Yang; Wang, Ruixue; Lin, Lexun; Chen, Sijia; Wang, Tianying; Zhong, Xiaoyan; Wu, Xiaoyu; Wang, Yan; Zhang, Fengmin; Zhao, Wenran; Zhong, Zhaohua

doi:10.3390/v8050131

Cited by 27 publications

(27 citation statements)

References 43 publications

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“…In HCV-infected cells, NS3/4A blocks the RIG-I signaling pathway in the early stages of autophagy and modulates the binding of mitochondria-associated immunity-associated GTPase family M (IRGM) to promote autophagy [43]. Similarly, JEV NS3 targets IRGM to modulate autophagy [44], and CBV2 protein 2B, whose C-terminal sequence plays a decisive role in autophagy, rearranges the cell membrane [45]. In our study, GFP-LC3 puncta accumulated in Nsp3-mCherry-, Nsp5-mCherry-and Nsp9-mCherry-transfected cells and p62 expression was increased, indicating that NSP3, NSP5 and NSP9 induced the formation of autophagosomes.…”

Section: Discussionmentioning

confidence: 99%

Involvement of PRRSV NSP3 and NSP5 in the autophagy process

Zhang

Chen

Guo

et al. 2019

Virol J

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BackgroundAutophagy is an essential process in eukaryotic cells in which autophagosomes form to deliver cellular organelles and long-lived proteins to lysosomes for degradation. Many studies have recently identified the regulatory mechanisms involved in the interaction between viral infection and autophagy.MethodsLC3 turnover and the proteins in the endoplasmic reticulum (ER) stress pathway were investigated using western blot analysis. The formation and degradation of autophagosomes were detected using immunofluorescence staining.ResultsAutophagy was activated by porcine reproductive and respiratory syndrome virus (PRRSV) NSP3, NSP5 and NSP9, which are two transmembrane proteins and an RNA-dependent RNA polymerase, respectively. The formation of autophagosomes was induced by NSP3 and NSP5 and developed from the ER; the fusion of these autophagosomes with lysosomes was limited. Although NSP3 and NSP5 are ER transmembrane proteins, these proteins did not activate the ER stress signaling pathways. In addition, the cytoplasmic domain of NSP3 plays a pivotal role in activating autophagy.ConclusionsThe data presented in this study reveal an important relationship between PRRSV NSPs and autophagy and provide new insights that improve our understanding of the involvement of PRRSV NSPs in the autophagy process.Electronic supplementary materialThe online version of this article (10.1186/s12985-019-1116-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Involvement of PRRSV NSP3 and NSP5 in the autophagy process

Zhang

Chen

Guo

et al. 2019

Virol J

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“…Phosphorylation of the hydrophobic motif ser 662 is an essential step in the activation of the cell survival and death regulation protein protein kinase C delta (PKCd) (53). The transmembrane hydrophobic sequences of CVB non-structure protein 2B is essential for the induction of autophagy (54). In view of this, we firstly predict the hydrophobic property of FMDV, PV and SVA proteins.…”

Section: Discussionmentioning

confidence: 99%

The glycine locating at random coil of picornaviruses VP3 enhances viral pathogenicity by targeting p53 to promote apoptosis and autophagy

Mao¹,

Yang²,

Sun³

et al. 2019

Preprint

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Picornaviruses, comprising important and widespread pathogens of humans and animals, have evolved to control apoptosis and autophagy for their replication and spread. However, the underlying mechanism of the association between apoptosis/autophage and viral pathogenicity remains unclear. In the present study, VP3 of picornaviruses was demonstrated to induce apoptosis and autophagy. Foot-and-mouth disease virus (FMDV), which served as a research model here, can strongly induce both apoptosis and autophagy in the skin lesions. By directly interacting with p53, FMDV-VP3 facilitates its phosphorylation and translocation, resulting in Bcl-2 family-mediated apoptosis and LC3-dependent autophagy. The single residue Gly129 of FMDV-VP3 plays a crucial role in apoptosis and autophagy induction and the interaction with p53. Consistently, the comparison of rescued FMDV with mutated Gly129 and parental virus showed that the Gly129 is indispensable for viral replication and pathogenicity. More importantly, the Gly129 locates at a bend region of random coil structure, the mutation of Gly to Ala remarkably shrunk the volume of viral cavity. Coincidentally, the Gly is conserved in the similarly location of other picornaviruses, including poliovirus (PV), enterovirus 71 (EV71), coxsackievirus (CV) and seneca valley virus (SVA). This study demonstrates that picornaviruses induce apoptosis and autophagy to facilitate its pathogenicity and the Gly is functional site, providing novel insights into picornavirus biology.

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“…Studies reported that some viruses, including polio virus [26], hepatitis C virus [27,28], dengue virus [29,30] can induce autophagy. Coxsackie virus can either inhibit autophagy or induce the formation of autophagosomes to increase viral replication [31,32]. Xi and the colleagues determined autophagy was induced by EV71 virus in RD-A cells, with an increase in the time course of infection (6h, 9h, 12h and 24h) by EV71, the conversion of LC3-I to LC3-II and the degradation of p62 increased accordingly [7].…”

Section: Discussionmentioning

confidence: 99%

“…Virus infection could induce autophagy, and many viral proteins can induce autophagy also [37][38][39][40]. A recent study showed that neither 2B, 2C, 3A, 3B, 3AB, 3C nor 3D could trigger autophagy individually [7].…”

Section: Discussionmentioning

confidence: 99%

Characteristics of Autophagy Induced by Enterovirus71 (EV71) Viral Protein

Li¹,

Jinxue²,

Liu³

et al. 2018

J Trop Dis

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Hand, Foot and Mouth Disease (HFMD) is a type of infectious disease that is more commonly seen in children under the age of 6 years. It was first reported in New Zealand in 1957, and then outbreaks occurred in Europe, America and Asia. In recent years, the incidence of HFMD in China is also on the rise. HFMD was caused by Coxsackievirus A16 (CVA16) and Human Enterovirus 71 (EV71) and other virus. CVA16 usually causes mild cases and is less harmful, while EV71 infection causes not only mild cases, but also severe and fatal cases; it has become a cause of concern. The mechanism of HFMD caused by EV71 virus is not completely clear. After it infects host cells, the EV71 virus genome undergoes replication, translation, assembly, and the release of virosomes. Some studies have reported that EV71 could induce host cell autophagy. Autophagy is a cellular process necessary for the lysosomal degradation and recycling of proteins and entire organelles. It can act as not only a defense mechanism to prevent environmental damage to cells, also induce cell death in eukaryotes. To explore the correlation and characteristics of EV71 virus, EV71 viral protein and autophagy, we used EV71 and recombinant plasmid pcDNA3.1 (+)-HA-X to infect human 293T cells, and we found that autophagy could be induced by EV71. With the prolongation of infection, autophagy presents a dynamic trend. And the protein that causes autophagy is structural protein VP1 and non-structural protein 2A.

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Protein 2B of Coxsackievirus B3 Induces Autophagy Relying on Its Transmembrane Hydrophobic Sequences

Cited by 27 publications

References 43 publications

Involvement of PRRSV NSP3 and NSP5 in the autophagy process

Involvement of PRRSV NSP3 and NSP5 in the autophagy process

The glycine locating at random coil of picornaviruses VP3 enhances viral pathogenicity by targeting p53 to promote apoptosis and autophagy

Characteristics of Autophagy Induced by Enterovirus71 (EV71) Viral Protein

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