Periplaneta fuliginosa densovirus nonstructural protein NS1 contains an endonuclease activity that is regulated by its phosphorylation

Han, Yajuan; Wang, Qinrong; Qiu, Yang; Wu, Wenzhe; He, Huihui; Zhang, Jiamin; Hu, Yuanyang; Zhou, Xi

doi:10.1016/j.virol.2012.12.006

Cited by 13 publications

(12 citation statements)

References 62 publications

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“…A cDNA fragment of the putative EoV helicase domain (amino acids [aa] 1374 to 1789 of polyprotein open reading frame [ORF]) of hepatitis C virus (HCV) NS3 protein was inserted into the vector pFastBacHTA-MBP. Briefly, pFastBacHTA-MBP vector originated from the vector pFastBacHTA (Invitrogen, Carlsbad, CA), into which the maltose-binding protein (MBP) was N-terminally fused by our laboratory as previously described (45)(46)(47)(48). Mutations were generated as described previously (44).…”

Section: Construction Of Recombinant Baculovirusesmentioning

confidence: 99%

The Nonstructural Protein 2C of a Picorna-Like Virus Displays Nucleic Acid Helix Destabilizing Activity That Can Be Functionally Separated from Its ATPase Activity

Cheng

Yang

Xia

et al. 2013

J Virol

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b Picorna-like viruses in the Picornavirales order are a large group of positive-strand RNA viruses that include numerous important pathogens for plants, insects, and humans. In these viruses, nonstructural protein 2C is one of the most conserved proteins and contains ATPase activity and putative RNA helicase activity. Here we expressed 2C protein of Ectropis obliqua picorna-like virus (EoV; genus Iflavirus, family Iflaviridae, order Picornavirales) in a eukaryotic expression system and determined that EoV 2C displays ATP-independent nucleic acid helix destabilizing and strand annealing acceleration activity in a concentration-dependent manner, indicating that this picornaviral 2C is more like an RNA chaperone than like the previously predicted RNA helicase. Our further characterization of EoV 2C revealed that divalent metal ions, such as Mg 2؉ and Zn 2؉ , inhibit 2C-mediated helix destabilization to different extents. Moreover, we determined that EoV 2C also contains ATPase activity like that of other picornaviral 2C proteins and further assessed the functional relevance between its RNA chaperone-like and ATPase activities using mutational analysis as well as their responses to Mg 2؉ . Our data show that, when one of the two 2C activities was dramatically inhibited or almost abolished, the other activity could remain intact, showing that the RNA chaperone-like and ATPase activities of EoV 2C can be functionally separated. This report reveals that a picorna-like virus 2C protein displays RNA helix destabilizing and strand annealing acceleration activity, which may be critical for picornaviral replication and pathogenesis, and should foster our understanding of picorna-like viruses and viral RNA chaperones.

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Section: Construction Of Recombinant Baculovirusesmentioning

confidence: 99%

The Nonstructural Protein 2C of a Picorna-Like Virus Displays Nucleic Acid Helix Destabilizing Activity That Can Be Functionally Separated from Its ATPase Activity

Cheng

Yang

Xia

et al. 2013

J Virol

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“…The genome of HBoV1 is a single-stranded DNA (ssDNA) of 5,543 nucleotides (nt) with a left-end hairpin (LEH) and a right-end hairpin (REH), which appear to be hybrid remnants of the animal bocaviruses bovine parvovirus 1 (BPV1) and minute virus of canine (MVC), respectively (15,(17)(18)(19). All parvoviruses encode a nonstructural protein NS1 (termed Rep in adeno-associated virus [AAV]) that is essential for viral DNA replication (20)(21)(22)(23)(24) and packaging of viral DNA into capsid (25)(26)(27). It may play other versatile roles, for example, in the transactivation of viral (28)(29)(30)(31) and cellular (32) gene expression, DNA damage response (33)(34)(35)(36), cell cycle arrest, apoptosis (37)(38)(39)(40), and/or the modulation of innate immunity (41).…”

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confidence: 99%

Structure of the NS1 Protein N-Terminal Origin Recognition/Nickase Domain from the Emerging Human Bocavirus

Tewary

Zhao

Shen

et al. 2013

J Virol

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Human bocavirus is a newly identified, globally prevalent, parvovirus that is associated with respiratory infection in infants and young children. Parvoviruses encode a large nonstructural protein 1 (NS1) that is essential for replication of the viral singlestranded DNA genome and DNA packaging and may play versatile roles in virus-host interactions. Here, we report the structure of the human bocavirus NS1 N-terminal domain, the first for any autonomous parvovirus. The structure shows an overall fold that is canonical to the histidine-hydrophobic-histidine superfamily of nucleases, which integrates two distinct DNA-binding sites: (i) a positively charged region mediated by a surface hairpin (residues 190 to 198) that is responsible for recognition of the viral origin of replication of the double-stranded DNA nature and (ii) the nickase active site that binds to the single-stranded DNA substrate for site-specific cleavage. The structure reveals an acidic-residue-rich subdomain that is present in bocavirus NS1 proteins but not in the NS1 orthologs in erythrovirus or dependovirus, which may mediate bocavirus-specific interaction with DNA or potential host factors. These results provide insights into recognition of the origin of replication and nicking of DNA during bocavirus genome replication. Mapping of variable amino acid residues of NS1s from four human bocavirus species onto the structure shows a scattered pattern, but the origin recognition site and the nuclease active site are invariable, suggesting potential targets for antivirals against this clade of highly diverse human viruses.

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“…and several studies have suggested that viral proteins are not active until phosphorylated by cellular kinase. The phosphorylation of NS1 protein from Periplaneta fuliginosa densovirus (PfDNV) triggers the activation of viral genome replication and transcription [48]. IE63 from vesicular stomatitis virus (VSV) is phosphorylated by host cellular cyclin-dependent kinase (CDK) 1 and CDK2, then translocates from the nucleus to the cytoplasm [49].…”

Section: Discussionmentioning

confidence: 99%

Grass Carp Reovirus (GCRV) Giving Its All to Suppress IFN Production by Countering MAVS-TBK1 Activation

Zhang

et al. 2019

Preprint

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As a crucial signaling pathway for interferon (IFN) production, the RIG-I-like receptor (RLR) axis is usually the host target of viruses to enhance viral infection. To date, though immune evasion methods to contrapose IFN production have been characterized for a series of terrestrial viruses, the strategies employed by fish viruses remain unclear. Here, we report that all grass carp reovirus (GCRV) proteins encoded by segments S1 to S11 interact with fish RLR factors, specifically for mitochondrial antiviral signaling protein-TANK-binding kinase 1 (MAVS-TBK1) signaling transduction, leading to decreased IFN expression. First, the GCRV viral proteins blunted the MAVS-induced expression of IFN but had little effect on TBK1-induced IFN expression. Subsequently, interestingly, co-immunoprecipitation experiments demonstrated that all GCRV viral proteins interacted with several RLR cascades, especially with TBK1. To further illustrate the mechanisms of these interactions between GCRV viral proteins and host RLRs, two of the viral proteins, NS79 (S4) and VP3 (S3), were selected as representative proteins for the study. The obtained data demonstrated that NS79 did not affect the stability of the host RLR protein, but was phosphorylated by gcTBK1, leading to the reduction of host substrate gcIRF3/7 phosphorylation. On the other hand, VP3 degraded gcMAVS and the degradation was significantly reversed by 3-MA. The biological effects of both NS79 and VP3 were consistently found to be related to the suppression of IFN expression and the promotion of viral evasion. Our findings shed light on the special evasion mechanism utilized by fish virus through IFN regulation, which might differ between fish and mammals. Author summaryThe RLR signaling pathway is crucial for IFN induction when host cells are infected with virus and RLR factors are targeted by virus. To date, the evasion mechanisms of fish viruses remain mysterious. In this study, we reveal that all 11 GCRV proteins interact with fish RLR factors and suppress the activation of MAVS-TBK1 signaling transduction, leading to the reduction of IFN expression. Two viral proteins were employed as examples to investigate the different evasion mechanisms of GCRV.These findings reveal the novel countermeasures used by fish virus to avoid the host IFN response.

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Periplaneta fuliginosa densovirus nonstructural protein NS1 contains an endonuclease activity that is regulated by its phosphorylation

Cited by 13 publications

References 62 publications

The Nonstructural Protein 2C of a Picorna-Like Virus Displays Nucleic Acid Helix Destabilizing Activity That Can Be Functionally Separated from Its ATPase Activity

The Nonstructural Protein 2C of a Picorna-Like Virus Displays Nucleic Acid Helix Destabilizing Activity That Can Be Functionally Separated from Its ATPase Activity

Structure of the NS1 Protein N-Terminal Origin Recognition/Nickase Domain from the Emerging Human Bocavirus

Grass Carp Reovirus (GCRV) Giving Its All to Suppress IFN Production by Countering MAVS-TBK1 Activation

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