Association of Japanese encephalitis virus NS3 protein with microtubules and tumour susceptibility gene 101 (TSG101) protein

Chiou, Chun Tang; Hu, Chih Chi Andrew; Chen, Pi Hsin; Liao, Ching Len; Lin, Yi-Ling; Wang, Jaang Jiun

doi:10.1099/vir.0.19201-0

Cited by 53 publications

(51 citation statements)

References 36 publications

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“…Microtubule dynamics play a critical role in ZIKV replication, as deduced from the strong antiviral effect of the microtubule-stabilizing drug paclitaxel (Figures 2G and S3E). Interestingly, DENV, WNV, JEV, and TBEV also induce cytoskeleton remodeling (Chen et al., 2008, Chiou et al., 2003, Ng and Hong, 1989, Růzek et al., 2009, Teo and Chu, 2014). In fact, treatment with a microtubule-destabilizing drug enhances DENV production (Chen et al., 2008), suggesting that DENV and ZIKV have developed similar cytoskeleton remodeling strategies.…”

Section: Discussionmentioning

confidence: 99%

Ultrastructural Characterization of Zika Virus Replication Factories

et al. 2017

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SummaryA global concern has emerged with the pandemic spread of Zika virus (ZIKV) infections that can cause severe neurological symptoms in adults and newborns. ZIKV is a positive-strand RNA virus replicating in virus-induced membranous replication factories (RFs). Here we used various imaging techniques to investigate the ultrastructural details of ZIKV RFs and their relationship with host cell organelles. Analyses of human hepatic cells and neural progenitor cells infected with ZIKV revealed endoplasmic reticulum (ER) membrane invaginations containing pore-like openings toward the cytosol, reminiscent to RFs in Dengue virus-infected cells. Both the MR766 African strain and the H/PF/2013 Asian strain, the latter linked to neurological diseases, induce RFs of similar architecture. Importantly, ZIKV infection causes a drastic reorganization of microtubules and intermediate filaments forming cage-like structures surrounding the viral RF. Consistently, ZIKV replication is suppressed by cytoskeleton-targeting drugs. Thus, ZIKV RFs are tightly linked to rearrangements of the host cell cytoskeleton.

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Section: Discussionmentioning

confidence: 99%

Ultrastructural Characterization of Zika Virus Replication Factories

et al. 2017

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“…Besides retroviruses, late domain motifs have also been identified in other enveloped viruses like rhabdoviruses (vesicular stomatitis virus, rabies virus) [15-17], filoviruses (ebola, marburg) [18-22], arenaviruses (lymphocytic choriomeningitis virus, lassa virus) [23,24], paramyxoviruses (Nipah virus, Sendai virus) [25,26] and DNA viruses like hepatitis B virus, vaccinia virus, herpes simplex virus-1 and Epstein Barr virus [27-33]. Amongst flaviviruses, the NS3 of Japanese encephalitis virus (JEV) has been shown to associate with Tsg101 [34] while the yellow fever virus (YFV) NS3 has been shown to interact with Alix [35] assisting in virus release. However, currently there is no information on the presence of late domains in WNV proteins.…”

Section: Introductionmentioning

confidence: 99%

Identification of conserved motifs in the Westnile virus envelope essential for particle secretion

et al. 2013

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BackgroundEnveloped viruses utilize cellular membranes to bud from infected cells. The process of virion assembly and budding is often facilitated by the presence of certain conserved motifs within viral proteins in conjunction with cellular factors. We hence examined the West Nile Virus (WNV) Envelope protein for the presence of any such motifs and their functional characterization.ResultsWe identified conserved 461PXAP464 and 349YCYL352 motifs in the WNV envelope glycoprotein bearing resemblance to retroviral late domains. Disruptive mutations of PXAP to LAAL and of the highly conserved Cys350 in the YCYL motif, led to a severe reduction in WNV particle production. Similar motifs in case of retroviruses are known to interact with components of host sorting machinery like PXAP with Tsg101 and YXXL with Alix. However, in the case of WNV, siRNA mediated depletion of Alix or Tsg101 did not have an effect on WNV release. Molecular modeling suggested that while the 461PXAP464 motif is surface accessible and could potentially interact with cellular proteins required for WNV assembly, the 349YCYL352 motif was found to be internal with Cys350 important for protein folding via disulphide bonding.ConclusionsThe conserved 461PXAP464 and 349YCYL352 motifs in the WNV envelope are indispensable for WNV particle production. Although these motifs bear sequence similarity to retroviral late domains and are essential for WNV assembly, they are functionally distinct suggesting that they are not the typical late domain like motifs of retroviruses and may play a role other than Alix/Tsg101 utilization/dependence.

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“…Several viral proteins of other viruses have been reported to interact with the cytoskeleton or cytoskeleton-associated proteins. For example, for both Japanese encephalitis virus and Kunjin virus, which, like HCV, belong to the family Flaviviridae, their NS3 proteins are associated with microtubules (10,42). The structural Gag matrix protein, which is a component of the reverse transcription complex of human immunodeficiency virus type 1, directly interacts with actin (8).…”

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confidence: 99%

Association of Hepatitis C Virus Replication Complexes with Microtubules and Actin Filaments Is Dependent on the Interaction of NS3 and NS5A

Lai

Jeng

Machida

et al. 2008

J Virol

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The hepatitis C virus (HCV) RNA replication complex (RC), which is composed of viral nonstructural (NS) proteins and host cellular proteins, replicates the viral RNA genome in association with intracellular membranes. Two viral NS proteins, NS3 and NS5A, are essential elements of the RC. Here, by using immunoprecipitation and fluorescence resonance energy transfer assays, we demonstrated that NS3 and NS5A interact with tubulin and actin. Furthermore, immunofluorescence microscopy and electron microscopy revealed that HCV RCs were aligned along microtubules and actin filaments in both HCV replicon cells and HCV-infected cells. In addition, the movement of RCs was inhibited when microtubules or actin filaments were depolymerized by colchicine and cytochalasin B, respectively. Based on our observations, we propose that microtubules and actin filaments provide the tracks for the movement of HCV RCs to other regions in the cell, and the molecular interactions between RCs and microtubules, or RCs and actin filaments, are mediated by NS3 and NS5A.Hepatitis C virus (HCV) is a major causative agent of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The positive-sense, single-stranded 9.6-kb RNA genome encodes a large polyprotein (Ͼ3,000 amino acids), which is processed by host and viral proteases into 10 structural and nonstructural (NS) proteins (17, 34). Most of the NS proteins (NS2, NS3, NS4A, NS4B, NS5A, and NS5B) of HCV were associated with the endoplasmic reticulum (ER) or other subcellular membranes when these proteins were expressed individually or as a polyprotein (23,24,40,52), with the probable exception of NS2, and are involved in HCV RNA replication (4,35,43). NS3 is a helicase and a serine protease, with the latter requiring a cofactor, NS4A. It is conceivable that the enzymatic activities of these proteins are key elements of the HCV replication complex (RC). The NS4B protein alone induces the membranous web in a membranous matrix; the newly synthesized HCV RNA also exists in these membranous webs (12, 16). NS5A is a phosphoprotein and an essential component of the HCV RC and plays an indispensable role in viral replication (4). NS5B is an RNA-dependent RNA polymerase. All of these NS proteins and the replicating HCV RNA, together with host proteins, are believed to form a membrane-associated HCV RC. We have further shown that HCV RNA synthesis occurs in a lipid raft membrane structure (2, 47). However, the full content and mechanisms of replication of HCV RC remain unclear.Our previous studies have shown that vesicle-associated membrane protein-associated protein (VAP) subtype A (VAP-A) and VAP subtype B (VAP-B) bind to both NS5A and NS5B and play a critical role in the formation of HCV RC

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Association of Japanese encephalitis virus NS3 protein with microtubules and tumour susceptibility gene 101 (TSG101) protein

Cited by 53 publications

References 36 publications

Ultrastructural Characterization of Zika Virus Replication Factories

Ultrastructural Characterization of Zika Virus Replication Factories

Identification of conserved motifs in the Westnile virus envelope essential for particle secretion

Association of Hepatitis C Virus Replication Complexes with Microtubules and Actin Filaments Is Dependent on the Interaction of NS3 and NS5A

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