The Newcastle disease virus V protein binds zinc

Steward, M. W.; Samson, A. C. R.; Errington, William; Emmerson, Peter T.

doi:10.1007/bf01322759

Cited by 60 publications

(35 citation statements)

References 24 publications

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“…Similar findings have also been reported for SV5, measles virus, and Newcastle disease virus (21,25,29). In the case of SV5, it was found, by using inductively coupled argon plasma atomic emission spectroscopy, that each molecule of the V protein binds two atoms of zinc (25).…”

Section: Discussionsupporting

confidence: 82%

“…This Vu region features a motif formed by seven cysteine residues (CX 3 CX 11 CXCX 2 CX 3 CX 2 C, where X refers to any amino acid residue), which are highly conserved in almost all the members of the subfamily Paramyxovirinae. The number and spacing of these cysteine residues resemble those of zinc finger structures and metalloproteins, and the V proteins of other members of the subfamily Paramyxovirinae, including simian virus 5 (SV5), measles virus, and Newcastle disease virus, have been shown to bind zinc (21,25,29). It is not known, however, whether the SeV V protein actually binds zinc ions.…”

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confidence: 99%

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Involvement of the Zinc-Binding Capacity of Sendai Virus V Protein in Viral Pathogenesis

Huang

Kiyotani

Fujii

et al. 2000

J Virol

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The V protein of Sendai virus (SeV) is nonessential to virus replication in cell culture but indispensable to viral pathogenicity in mice. The highly conserved cysteine-rich zinc finger-like domain in its carboxyl terminus is believed to be responsible for this viral pathogenicity. In the present study, we showed that the cysteine-rich domain of the SeV V protein could actually bind zinc by using glutathione-S-transferase fusion proteins. When the seven conserved cysteine residues at positions 337, 341, 353, 355, 358, 362, and 365 were replaced individually, the zinc-binding capacities of the mutant proteins were greatly impaired, ranging from 22 to 68% of that of the wild type. We then recovered two mutant SeVs from cDNA, which have V-C 341 S and V-C 365 R mutations and represent maximal and minimal zinc-binding capacities among the corresponding mutant fusion proteins, respectively. The mutant viruses showed viral protein synthesis and growth patterns similar to those of wild-type SeV in cultured cells. However, the mutant viruses were strongly attenuated in mice in a way similar to that of SeV V ⌬C , which has a truncated V protein lacking the cysteine-rich domain, by exhibiting earlier viral clearance from the mouse lung and less virulence to mice. We therefore conclude that the zinc-binding capacity of the V protein is involved in viral pathogenesis.Sendai virus (SeV), which belongs to the genus Respirovirus in the family Paramyxoviridae, is a respiratory tract pathogen of rodents. Like other members within the order Mononegavirales, it is an enveloped virus with a single-stranded, negativesense RNA genome of approximately 15.4 kb. The arrangement of the SeV genome starts with a short 3Ј leader sequence, followed by six genes encoding the structural proteins, including N (nucleocapsid), P (phosphoprotein), M (matrix), F (fusion), HN (hemagglutinin-neuraminidase), and L (large) proteins and terminates with a 5Ј trailer sequence (19).Among the six genes, the P gene was found to be unique in that it encodes not a single but multiple proteins. The colinear transcript encodes the P protein as well as the C, CЈ, Y 1 , and Y 2 proteins; these four proteins are translated in a shifted frame by alternative translational starts. The P gene also directs synthesis of an accessory mRNA for the V protein by inserting a pseudotemplated G residue at the specific editing site (30, 31). Consequently, the V and P proteins have the same 317 residues at the amino terminus (the P/V common region), while the V protein contains a 67-residue unique carboxyl terminus (the Vu region). This Vu region features a motif formed by seven cysteine residues (CX 3 CX 11 CXCX 2 CX 3 CX 2 C, where X refers to any amino acid residue), which are highly conserved in almost all the members of the subfamily Paramyxovirinae. The number and spacing of these cysteine residues resemble those of zinc finger structures and metalloproteins, and the V proteins of other members of the subfamily Paramyxovirinae, including simian virus 5 (SV5), measles virus, ...

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Section: Discussionsupporting

confidence: 82%

mentioning

confidence: 99%

Involvement of the Zinc-Binding Capacity of Sendai Virus V Protein in Viral Pathogenesis

Huang

Kiyotani

Fujii

et al. 2000

J Virol

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“…The matrix protein (M) is involved in the budding process of the newly formed virus particles (Peeples et al , 1992), while the haemagglutinin-neuraminidase (HN) and fusion protein (F), two glycoproteins anchored in the virion envelope, are involved in the binding and/or fusion to the host cell membrane, and, for HN, in the release of the newly formed virus particles (Yusoff & Tan, 2001). The P gene also encodes two non-structural proteins, called V and W, which seem to be involved in the pathogenesis of the virus (Steward et al , 1995;Mebatsion et al , 2001;Park et al , 2003).…”

Section: Introductionmentioning

confidence: 99%

Molecular study of the quasispecies evolution of a typical pigeon paramyxovirus type 1 after serial passages in pigeons by contact

Barbezange

Jestin

2005

Avian Pathology

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The quasispecies nature of a typical pigeon paramyxovirus type 1 (pPMV-1) was, for the first time, studied under conditions close to the natural infectious environment. The virus was serially passaged in pigeons by successive contacts. Viral heterogeneity was analysed in the kidneys and brain of five pigeons from the last contact, by reverse transcriptase-polymerase chain reactions performed on RNA directly extracted from the organ and targeting the P and HN genes of the virus. The viral diversity following in vivo passage was found to be different from that in the inoculum, but demonstrated the reality of the quasispecies concept for pPMV-1 strains. Moreover, some aberrant genomic RNAs comprising insertions in the P gene editing site or deletions in the HN gene were also detected, with possible consequences for the pathogenicity and infectivity of the virus.

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“…Paramyxovirus V proteins are composed of an N-terminal domain that is shared with the P and W/I proteins and a unique, highly conserved C-terminal domain (due to P gene mRNA editing) that is approximately 50% identical in amino acid sequence between all these viruses. Paramyxovirus V proteins have no cellular homologues but are readily identifiable by seven conserved cysteines at their C termini that bind two atoms of zinc (13,34,40). These conserved Cys residues play a critical role in specifically binding to DDB1 (1,23).…”

mentioning

confidence: 99%

Identification of Paramyxovirus V Protein Residues Essential for STAT Protein Degradation and Promotion of Virus Replication

Nishio

Tsurudome

Ito

et al. 2005

J Virol

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Some paramyxovirus V proteins induce STAT protein degradation, and the amino acids essential for this process in the human parainfluenza virus type 2 (hPIV2) V protein have been studied. Various recombinant hPIV2s and cell lines constitutively expressing various mutant V proteins were generated. We found that V proteins with replacement of Cys residues of the Cys cluster were still able to bind STATs but were unable to induce their degradation. The hPIV2 V protein binds STATs via a W-(X) 3 -W-(X) 9 -W Trp motif located just upstream of the Cys cluster. Replacements of two or more Trp residues in this motif resulted in a failure to form a V/STAT2 complex. We have also identified two Phe residues of the hPIV2 V protein that are essential for STAT degradation, namely, Phe207, lying within the Cys cluster, and Phe143, in the P/V common region of the protein. Interestingly, infection of BHK cells with hPIV2 led to the specific degradation of STAT1 and not STAT2. Other evidence for the cell species specificity of hPIV2-induced STAT degradation is presented. Finally, a V-minus hPIV2, which can express only the P protein from its P gene, was generated and partially characterized. In contrast to V-minus viruses of other paramyxovirus genera, this V-minus rubulavirus was highly debilitated, and its growth even in Vero cells was very limited. The structural rubulavirus V proteins, as expected, are thus clearly important in promoting virus growth, independent of their anti-interferon (IFN) activity. Interestingly, many of the residues that are essential for anti-IFN activity, e.g., the Cys of this cluster and Phe207 within this cluster, as well as the Trp of this motif, are also essential for promoting virus growth.The interferon (IFN) system is the first line of host defense against virus infection. Viruses of the Paramyxovirinae, similarly to other viruses, have evolved proteins that specifically inhibit IFN-induced innate antiviral responses, at least in part through direct inhibition of cellular STAT proteins that are responsible for IFN signal transduction. The V proteins encoded by the rubulaviruses simian virus 5 (SV5), SV41, and mumps virus (MuV) and by Newcastle disease virus (NDV, an avulavirus) block IFN signaling by targeting STAT1 for degradation (1,5,6,14,20,25,33,45,46,49,51), whereas the V protein of human parainfluenza virus type 2 (hPIV2, a rubulavirus) targets STAT2 for degradation (25,32). Moreover, the V proteins of measles virus (morbillivirus) and Nipah virus and Hendra virus (henipaviruses) have been shown to inhibit IFN signaling by preventing STAT1 and STAT2 nuclear accumulation (30,37,38,41). Sendai virus (SeV) and hPIV3 also block IFN signaling, and this anti-IFN ability has been shown to be a property of these respirovirus C proteins (7,8,10,11,17,19,42). In cells that are highly IFN competent, the Sendai virus C protein also induces the intracellular loss of STAT1 (9). The rubulavirus V protein-dependent degradation of STAT proteins involves degradation complexes that contain the V protein, STA...

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The Newcastle disease virus V protein binds zinc

Cited by 60 publications

References 24 publications

Involvement of the Zinc-Binding Capacity of Sendai Virus V Protein in Viral Pathogenesis

Involvement of the Zinc-Binding Capacity of Sendai Virus V Protein in Viral Pathogenesis

Molecular study of the quasispecies evolution of a typical pigeon paramyxovirus type 1 after serial passages in pigeons by contact

Identification of Paramyxovirus V Protein Residues Essential for STAT Protein Degradation and Promotion of Virus Replication

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