The Association of Receptor of Activated Protein Kinase C 1(RACK1) with Infectious Bursal Disease Virus Viral Protein VP5 and Voltage-dependent Anion Channel 2 (VDAC2) Inhibits Apoptosis and Enhances Viral Replication

Lin, Wencheng; Zhang, Zhiqiang; Xu, Zhichao; Wang, Bin; Li, Xiaoqi; Cao, Hong; Wang, Yongqiang; Zheng, Shijun

doi:10.1074/jbc.m114.585687

Cited by 56 publications

(47 citation statements)

References 62 publications

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“…Viruses are known to modulate apoptosis at the mitochondrial level via multiple strategies (36)(37)(38)(39)(40). Previously, VDAC2 (a member of the VDAC family) was reported to be involved in regulating IBDV replication through modulating VP5-induced apoptosis (23,41). In this study, we demonstrated that the expression of VDAC1 is upregulated following IBDV infection.…”

Section: Discussionmentioning

confidence: 55%

Voltage-Dependent Anion Channel 1 Interacts with Ribonucleoprotein Complexes To Enhance Infectious Bursal Disease Virus Polymerase Activity

Han

Zeng

Yao

et al. 2017

J Virol

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Infectious bursal disease virus (IBDV) is a double-stranded RNA (dsRNA) virus. Segment A contains two overlapping open reading frames (ORFs), which encode viral proteins VP2, VP3, VP4, and VP5. Segment B contains one ORF and encodes the viral RNA-dependent RNA polymerase, VP1. IBDV ribonucleoprotein complexes are composed of VP1, VP3, and dsRNA and play a critical role in mediating viral replication and transcription during the virus life cycle. In the present study, we identified a cellular factor, VDAC1, which was upregulated during IBDV infection and found to mediate IBDV polymerase activity. VDAC1 senses IBDV infection by interacting with viral proteins VP1 and VP3. This association is caused by RNA bridging, and all three proteins colocalize in the cytoplasm. Furthermore, small interfering RNA (siRNA)-mediated downregulation of VDAC1 resulted in a reduction in viral polymerase activity and a subsequent decrease in viral yield. Moreover, overexpression of VDAC1 enhanced IBDV polymerase activity. We also found that the viral protein VP3 can replace segment A to execute polymerase activity. A previous study showed that mutations in the C terminus of VP3 directly influence the formation of VP1-VP3 complexes. Our immunoprecipitation experiments demonstrated that protein-protein interactions between VDAC1 and VP3 and between VDAC1 and VP1 play a role in stabilizing the interaction between VP3 and VP1, further promoting IBDV polymerase activity.IMPORTANCE The cellular factor VDAC1 controls the entry and exit of mitochondrial metabolites and plays a pivotal role during intrinsic apoptosis by mediating the release of many apoptogenic molecules. Here we identify a novel role of VDAC1, showing that VDAC1 interacts with IBDV ribonucleoproteins (RNPs) and facilitates IBDV replication by enhancing IBDV polymerase activity through its ability to stabilize interactions in RNP complexes. To our knowledge, this is the first report that VDAC1 is specifically involved in regulating IBDV RNA polymerase activity, providing novel insight into virus-host interactions.

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Section: Discussionmentioning

confidence: 55%

Voltage-Dependent Anion Channel 1 Interacts with Ribonucleoprotein Complexes To Enhance Infectious Bursal Disease Virus Polymerase Activity

Han

Zeng

Yao

et al. 2017

J Virol

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“…Specifically VDAC2 has been linked to many cellular proteins, including Bak [17,64,65], stAR [35], Metaxin2 [66], Bcl-xS [67], RyR2 [68], eNOS (nitric oxide synthesize) [69], GSK3β [70], tubulin [71,72], Bax [73], BECN1-BCL2L1 [74] and Mcl1 [75]. Also, VP5, a viral protein from infectious bursal disease virus, has been demonstrated to interact with VDAC2 and Rack1 (receptor of activated protein kinase C1) in host cells [76,77]. Lastly, VDAC2 was identified as a target of chemicals, Erastin [78], an anti-tumor reagent and Efsevin [79].…”

Section: Interaction Partnersmentioning

confidence: 99%

“…This protein was suggested to support apoptosis induction in host cells by restraining Rack1, which is an antiapoptotic protein, and VDAC2. However, the role of VDAC2 in this context is not clear [76,77]. …”

Section: Vdac2's Other Functionsmentioning

confidence: 99%

VDAC2-specific cellular functions and the underlying structure

Naghdi

Hajnóczky

2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Voltage Dependent Anion-selective Channel 2 (VDAC2) contributes to oxidative metabolism by sharing a role in solute transport across the outer mitochondrial membrane (OMM) with other isoforms of the VDAC family, VDAC1 and VDAC3. Recent studies revealed that VDAC2 also has a distinctive role in mediating sarcoplasmic reticulum to mitochondria local Ca2+ transport at least in cardiomyocytes, which is unlikely to be explained simply by the expression level of VDAC2. Furthermore, a strictly isoform-dependent VDAC2 function was revealed in the mitochondrial import and OMM-permeabilizing function of pro-apoptotic Bcl-2 family proteins, primarily Bak in many cell types. In addition, emerging evidence indicates a variety of other isoform-specific engagements for VDAC2. Since VDAC isoforms display 75% sequence similarity, the distinctive structure underlying VDAC2-specific functions is an intriguing problem. In this paper we summarize studies of VDAC2 structure and functions, which suggest a fundamental and exclusive role for VDAC2 in health and disease. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou.

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“…the regulatory subunit of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) [21], and the mitochondrial voltage-dependent anion channel 2 (VDAC2) protein [22, 23]. The potential involvement of VP5 on apoptosis is under debate with reports supporting both a pro- and anti-apoptotic roles for this protein [20–22, 24].…”

Section: Introductionmentioning

confidence: 99%

Non-Lytic Egression of Infectious Bursal Disease Virus (IBDV) Particles from Infected Cells

et al. 2017

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Infectious bursal disease virus (IBDV), a member of the Birnaviridae family, is responsible for a devastating immunosuppressive disease affecting juvenile domestic chickens. IBDV particles are naked icosahedrons enclosing a bipartite double-stranded RNA genome harboring three open reading frames (ORF). One of these ORFs codes for VP5, a non-structural polypeptide dispensable for virus replication in tissue culture but essential for IBDV pathogenesis. Using two previously described recombinant viruses, whose genomes differ in a single nucleotide, expressing or not the VP5 polypeptide, we have analyzed the role of this polypeptide during the IBDV replication process. Here, we show that VP5 is not involved in house-keeping steps of the virus replication cycle; i.e. genome transcription/replication, protein translation and virus assembly. Although infection with the VP5 expressing and non-expressing viruses rendered similar intracellular infective progeny yields, striking differences were detected on the ability of their progenies to exiting infected cells. Experimental data shows that the bulk of the VP5-expressing virus progeny efficiently egresses infected cells during the early phase of the infection, when viral metabolism is peaking and virus-induced cell death rates are as yet minimal, as determined by qPCR, radioactive protein labeling and quantitative real-time cell death analyses. In contrast, the release of the VP5-deficient virus progeny is significantly abridged and associated to cell death. Taken together, data presented in this report show that IBDV uses a previously undescribed VP5-dependent non-lytic egress mechanism significantly enhancing the virus dissemination speed. Ultrastructural analyses revealed that newly assembled IBDV virions associate to a vesicular network apparently facilitating their trafficking from virus assembly factories to the extracellular milieu, and that this association requires the expression of the VP5 polypeptide.

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The Association of Receptor of Activated Protein Kinase C 1(RACK1) with Infectious Bursal Disease Virus Viral Protein VP5 and Voltage-dependent Anion Channel 2 (VDAC2) Inhibits Apoptosis and Enhances Viral Replication

Cited by 56 publications

References 62 publications

Voltage-Dependent Anion Channel 1 Interacts with Ribonucleoprotein Complexes To Enhance Infectious Bursal Disease Virus Polymerase Activity

Voltage-Dependent Anion Channel 1 Interacts with Ribonucleoprotein Complexes To Enhance Infectious Bursal Disease Virus Polymerase Activity

VDAC2-specific cellular functions and the underlying structure

Non-Lytic Egression of Infectious Bursal Disease Virus (IBDV) Particles from Infected Cells

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