Functional Analyses of the Three Simian Hemorrhagic Fever Virus Nonstructural Protein 1 Papain-Like Proteases

Vatter, Heather A.; Han, Dongyi; Donaldson, Eric F.; Radu, Gertrud U.; Maines, Taronna R.; Brinton, Margo A.

doi:10.1128/jvi.01020-14

Cited by 11 publications

(18 citation statements)

References 28 publications

(60 reference statements)

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“…While EAV nsp1 contains a single active protease named PLP1, PRRSV and LDV nsp1 contain two protease domains each: PLP1α and PLP1β. In the case of SHFV, there are three functional PLPs in nsp1 that release nsp1α, β, and γ [191,194]. The PLP2 protease in nsp2 of arteriviruses was shown to cleave the nsp2-3 junction [195].…”

Section: Arteriviridaementioning

confidence: 99%

Structure and Function of Viral Deubiquitinating Enzymes

Bailey-Elkin

Knaap

Kikkert

et al. 2017

Journal of Molecular Biology

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Post-translational modification of cellular proteins by ubiquitin regulates numerous cellular processes, including innate and adaptive immune responses. Ubiquitin-mediated control over these processes can be reversed by cellular deubiquitinating enzymes (DUBs), which remove ubiquitin from cellular targets and depolymerize polyubiquitin chains. The importance of protein ubiquitination to host immunity has been underscored by the discovery of viruses that encode proteases with deubiquitinating activity, many of which have been demonstrated to actively corrupt cellular ubiquitin-dependent processes to suppress innate antiviral responses and promote viral replication. DUBs have now been identified in diverse viral lineages, and their characterization is providing valuable insights into virus biology and the role of the ubiquitin system in host antiviral mechanisms. Here, we provide an overview of the structural biology of these fascinating viral enzymes and their role innate immune evasion and viral replication.

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Section: Arteriviridaementioning

confidence: 99%

Structure and Function of Viral Deubiquitinating Enzymes

Bailey-Elkin

Knaap

Kikkert

et al. 2017

Journal of Molecular Biology

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“…The number of active PLP domains varies per virus species (e.g. 2 for EAV, 3 for PRRSV and LDV, and 4 for SHFV) and these proteases all reside in the first 850 residues upstream of TM1, where each of them processes a single downstream cleavage site (Vatter et al, 2014). In the case of EAV, the PLPs located in nsp1 and nsp2 (called PLP1␤ and PLP2) both swiftly process a single site in the polyprotein (the nsp1/nsp2 and nsp2/nsp3 junctions, respectively; Fig.…”

Section: Arterivirus Biologymentioning

confidence: 99%

Biogenesis and architecture of arterivirus replication organelles

Oudshoorn

Koster

et al. 2016

Virus Research

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All eukaryotic positive-stranded RNA (+RNA) viruses appropriate host cell membranes and transform them into replication organelles, specialized micro-environments that are thought to support viral RNA synthesis. Arteriviruses (order Nidovirales) belong to the subset of +RNA viruses that induce double-membrane vesicles (DMVs), similar to the structures induced by e.g. coronaviruses, picornaviruses and hepatitis C virus. In the last years, electron tomography has revealed substantial differences between the structures induced by these different virus groups. Arterivirus-induced DMVs appear to be closed compartments that are continuous with endoplasmic reticulum membranes, thus forming an extensive reticulovesicular network (RVN) of intriguing complexity. This RVN is remarkably similar to that described for the distantly related coronaviruses (also order Nidovirales) and sets them apart from other DMV-inducing viruses analysed to date. We review here the current knowledge and open questions on arterivirus replication organelles and discuss them in the light of the latest studies on other DMV-inducing viruses, particularly coronaviruses. Using the equine arteritis virus (EAV) model system and electron tomography, we present new data regarding the biogenesis of arterivirus-induced DMVs and uncover numerous putative intermediates in DMV formation. We generated cell lines that can be induced to express specific EAV replicase proteins and showed that DMVs induced by the transmembrane proteins nsp2 and nsp3 form an RVN and are comparable in topology and architecture to those formed during viral infection. Co-expression of the third EAV transmembrane protein (nsp5), expressed as part of a self-cleaving polypeptide that mimics viral polyprotein processing in infected cells, led to the formation of DMVs whose size was more homogenous and closer to what is observed upon EAV infection, suggesting a regulatory role for nsp5 in modulating membrane curvature and DMV formation.

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“…The function of the recently discovered ORF5a, a possible additional minor structural protein, is not known, but knocking out the expression of this protein in the EAV genome reduced the virus yield (21,22). Among arteriviruses, SHFV has the largest genome at ∼15.7 kb and encodes an additional nsp1 protein (nsp1γ) and an extra set of minor structural proteins (GP2′, GP3′, GP4′, and E′) (23,24). The functions of these additional minor structural proteins are not currently known, but each is required for the production of infectious extracellular virions (25).…”

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confidence: 99%

Expanded subgenomic mRNA transcriptome and coding capacity of a nidovirus

Han

Madden

Morantz

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Members of the order Nidovirales express their structural protein ORFs from a nested set of 3' subgenomic mRNAs (sg mRNAs), and for most of these ORFs, a single genomic transcription regulatory sequence (TRS) was identified. Nine TRSs were previously reported for the arterivirus (SHFV). In the present study, which was facilitated by next-generation sequencing, 96 SHFV body TRSs were identified that were functional in both infected MA104 cells and macaque macrophages. The abundance of sg mRNAs produced from individual TRSs was consistent over time in the two different cell types. Most of the TRSs are located in the genomic 3' region, but some are in the 5' ORF1a/1b region and provide alternative sources of nonstructural proteins. Multiple functional TRSs were identified for the majority of the SHFV 3' ORFs, and four previously identified TRSs were found not to be the predominant ones used. A third of the TRSs generated sg mRNAs with variant leader-body junction sequences. Sg mRNAs encoding E', GP2, or ORF5a as their 5' ORF as well as sg mRNAs encoding six previously unreported alternative frame ORFs or 14 previously unreported C-terminal ORFs of known proteins were also identified. Mutation of the start codon of two C-terminal ORFs in an infectious clone reduced virus yield. Mass spectrometry detected one previously unreported protein and suggested translation of some of the C-terminal ORFs. The results reveal the complexity of the transcriptional regulatory mechanism and expanded coding capacity for SHFV, which may also be characteristic of other nidoviruses.

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Functional Analyses of the Three Simian Hemorrhagic Fever Virus Nonstructural Protein 1 Papain-Like Proteases

Cited by 11 publications

References 28 publications

Structure and Function of Viral Deubiquitinating Enzymes

Structure and Function of Viral Deubiquitinating Enzymes

Biogenesis and architecture of arterivirus replication organelles

Expanded subgenomic mRNA transcriptome and coding capacity of a nidovirus

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