scholarly journals Expression of Concern: Active participation of cellular chaperone Hsp90 in regulating the function of rotavirus nonstructural protein 3 (NSP3).

2019 ◽  
Vol 294 (41) ◽  
pp. 15118-15118
Keyword(s):  
Nonstructural Protein ◽  
Active Participation ◽  
Nonstructural Protein 3

scholarly journals Withdrawal: Active participation of cellular chaperone Hsp90 in regulating the function of rotavirus nonstructural protein 3 (NSP3).

2020 ◽  
Vol 295 (39) ◽  
pp. 13696-13696
Author(s):  
Dipanjan Dutta ◽  
Shiladitya Chattopadhyay ◽  
Parikshit Bagchi ◽  
Umesh Chandra Halder ◽  
Satabdi Nandi ◽  
...  
Keyword(s):  
Nonstructural Protein ◽  
Active Participation ◽  
Nonstructural Protein 3

scholarly journals p53 down-regulates SARS coronavirus replication and is targeted by the SARS-unique domain and PLprovia E3 ubiquitin ligase RCHY1

2016 ◽  
Vol 113 (35) ◽  
pp. E5192-E5201 ◽  
Author(s):  
Yue Ma-Lauer ◽  
Javier Carbajo-Lozoya ◽  
Marco Y. Hein ◽  
Marcel A. Müller ◽  
Wen Deng ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Nonstructural Protein ◽  
E3 Ubiquitin Ligase ◽  
Ring Finger ◽  
Immune Recognition ◽  
Major Player ◽  
Nonstructural Protein 3 ◽  
Human Coronaviruses ◽  
Unique Domain

Highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) has developed strategies to inhibit host immune recognition. We identify cellular E3 ubiquitin ligase ring-finger and CHY zinc-finger domain-containing 1 (RCHY1) as an interacting partner of the viral SARS-unique domain (SUD) and papain-like protease (PLpro), and, as a consequence, the involvement of cellular p53 as antagonist of coronaviral replication. Residues 95–144 of RCHY1 and 389–652 of SUD (SUD-NM) subdomains are crucial for interaction. Association with SUD increases the stability of RCHY1 and augments RCHY1-mediated ubiquitination as well as degradation of p53. The calcium/calmodulin-dependent protein kinase II delta (CAMK2D), which normally influences RCHY1 stability by phosphorylation, also binds to SUD. In vivo phosphorylation shows that SUD does not regulate phosphorylation of RCHY1 via CAMK2D. Similarly to SUD, the PLpros from SARS-CoV, MERS-CoV, and HCoV-NL63 physically interact with and stabilize RCHY1, and thus trigger degradation of endogenous p53. The SARS-CoV papain-like protease is encoded next to SUD within nonstructural protein 3. A SUD–PLprofusion interacts with RCHY1 more intensively and causes stronger p53 degradation than SARS-CoV PLproalone. We show that p53 inhibits replication of infectious SARS-CoV as well as of replicons and human coronavirus NL63. Hence, human coronaviruses antagonize the viral inhibitor p53 via stabilizing RCHY1 and promoting RCHY1-mediated p53 degradation. SUD functions as an enhancer to strengthen interaction between RCHY1 and nonstructural protein 3, leading to a further increase in in p53 degradation. The significance of these findings is that down-regulation of p53 as a major player in antiviral innate immunity provides a long-sought explanation for delayed activities of respective genes.

scholarly journals Persistent Replication of a Chikungunya Virus Replicon in Human Cells Is Associated with Presence of Stable Cytoplasmic Granules Containing Nonstructural Protein 3

2018 ◽  
Vol 92 (16) ◽  
Author(s):  
Roland Remenyi ◽  
Yanni Gao ◽  
Ruth E. Hughes ◽  
Alistair Curd ◽  
Carsten Zothner ◽  
...  
Keyword(s):  
Chronic Disease ◽  
Chikungunya Virus ◽  
Protein Complexes ◽  
Nonstructural Protein ◽  
Viral Proteins ◽  
Human Cells ◽  
Chikv Infection ◽  
Cytoplasmic Granules ◽  
Nonstructural Protein 3

ABSTRACTChikungunya virus (CHIKV), a mosquito-borne human pathogen, causes a disabling disease characterized by severe joint pain that can persist for weeks, months, or even years in patients. The nonstructural protein 3 (nsP3) plays essential roles during acute infection, but little is known about the function of nsP3 during chronic disease. Here, we used subdiffraction multicolor microscopy for spatial and temporal analysis of CHIKV nsP3 within human cells that persistently replicate replicon RNA. Round cytoplasmic granules of various sizes (i) contained nsP3 and stress granule assembly factors 1 and 2 (G3BP1/2), (ii) were next to double-stranded RNA foci and nsP1-positive structures, and (iii) were close to the nuclear membrane and the nuclear pore complex protein Nup98. Analysis of protein turnover and mobility by live-cell microscopy revealed that the granules could persist for hours to days, accumulated newly synthesized protein, and moved through the cytoplasm at various speeds. The granules also had a static internal architecture and were stable in cell lysates. Refractory cells that had cleared the noncytotoxic replicon regained the ability to respond to arsenite-induced stress. In summary, nsP3 can form uniquely stable granular structures that persist long-term within the host cell. This continued presence of viral and cellular protein complexes has implications for the study of the pathogenic consequences of lingering CHIKV infection and the development of strategies to mitigate the burden of chronic musculoskeletal disease brought about by a medically important arthropod-borne virus (arbovirus).IMPORTANCEChikungunya virus (CHIKV) is a reemerging alphavirus transmitted by mosquitos and causes transient sickness but also chronic disease affecting muscles and joints. No approved vaccines or antivirals are available. Thus, a better understanding of the viral life cycle and the role of viral proteins can aid in identifying new therapeutic targets. Advances in microscopy and development of noncytotoxic replicons (A. Utt, P. K. Das, M. Varjak, V. Lulla, A. Lulla, A. Merits, J Virol 89:3145–3162, 2015,https://doi.org/10.1128/JVI.03213-14) have allowed researchers to study viral proteins within controlled laboratory environments over extended durations. Here we established human cells that stably replicate replicon RNA and express tagged nonstructural protein 3 (nsP3). The ability to track nsP3 within the host cell and during persistent replication can benefit fundamental research efforts to better understand long-term consequences of the persistence of viral protein complexes and thereby provide the foundation for new therapeutic targets to control CHIKV infection and treat chronic disease symptoms.

scholarly journals Global Origin and Transmission of Hepatitis C Virus Nonstructural Protein 3 Q80K Polymorphism

2014 ◽  
Vol 211 (8) ◽  
pp. 1288-1295 ◽  
Author(s):  
Rosemary M. McCloskey ◽  
Richard H. Liang ◽  
Jeffrey B. Joy ◽  
Mel Krajden ◽  
Julio S. G. Montaner ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Nonstructural Protein ◽  
Nonstructural Protein 3

scholarly journals Proteomics Analysis Unravels the Functional Repertoire of Coronavirus Nonstructural Protein 3

2008 ◽  
Vol 82 (11) ◽  
pp. 5279-5294 ◽  
Author(s):  
Benjamin W. Neuman ◽  
Jeremiah S. Joseph ◽  
Kumar S. Saikatendu ◽  
Pedro Serrano ◽  
Amarnath Chatterjee ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Metal Ion ◽  
Rna Binding ◽  
Virus Assembly ◽  
Nonstructural Protein ◽  
Domain Architecture ◽  
Complete Characterization ◽  
Functional Domain ◽  
Metal Ion Binding ◽  
Nonstructural Protein 3

ABSTRACT Severe acute respiratory syndrome (SARS) coronavirus infection and growth are dependent on initiating signaling and enzyme actions upon viral entry into the host cell. Proteins packaged during virus assembly may subsequently form the first line of attack and host manipulation upon infection. A complete characterization of virion components is therefore important to understanding the dynamics of early stages of infection. Mass spectrometry and kinase profiling techniques identified nearly 200 incorporated host and viral proteins. We used published interaction data to identify hubs of connectivity with potential significance for virion formation. Surprisingly, the hub with the most potential connections was not the viral M protein but the nonstructural protein 3 (nsp3), which is one of the novel virion components identified by mass spectrometry. Based on new experimental data and a bioinformatics analysis across the Coronaviridae, we propose a higher-resolution functional domain architecture for nsp3 that determines the interaction capacity of this protein. Using recombinant protein domains expressed in Escherichia coli, we identified two additional RNA-binding domains of nsp3. One of these domains is located within the previously described SARS-unique domain, and there is a nucleic acid chaperone-like domain located immediately downstream of the papain-like proteinase domain. We also identified a novel cysteine-coordinated metal ion-binding domain. Analyses of interdomain interactions and provisional functional annotation of the remaining, so-far-uncharacterized domains are presented. Overall, the ensemble of data surveyed here paint a more complete picture of nsp3 as a conserved component of the viral protein processing machinery, which is intimately associated with viral RNA in its role as a virion component.

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