Measles Virus V Protein Binds Zinc

Liston, Peter; Briedis, Dalius J.

doi:10.1006/viro.1994.1050

Cited by 97 publications

(61 citation statements)

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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: 69%

“…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: 69%

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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“…Thus, it seems that most if not all P gene accessory proteins have evolved for roles in immune evasion as important pathogenicity factors [24][25][26][27][28] . Consistent with important roles in infection, V proteins show high conservation in the unique C-terminal region ( Figure 2) [29][30][31] , including absolute conservation of seven conserved cysteine residues and a histidine, which form a zinc-finger domain (highlighted in Figure 2). In the parainfluenza virus 5 (PIV5) V protein (Rubulavirus genus), two zinc atoms are coordinated by two loops, incorporating V residues H171, C190, C215, C218, and C194, C206, C208, C211 respectively [31,32] , and mutations of these residues disrupt certain IFN inhibitory functions (see below), although the role of zincbinding is not known.…”

Section: Paramyxovirus P Genementioning

confidence: 90%

Paramyxovirus evasion of innate immunity: Diverse strategies for common targets

Audsley

Moseley²

2013

WJV

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“…The V protein C-terminal domain contains seven cysteine residues (resembling a zinc finger domain) and binds atomic zinc (31,40,48,53). The V protein of SV5 interacts with soluble nucleocapsid protein (41), and the N-terminal domain of V binds RNA through a basic region (29).…”

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confidence: 99%

Conserved Cysteine-Rich Domain of Paramyxovirus Simian Virus 5 V Protein Plays an Important Role in Blocking Apoptosis

Sun¹,

Rothermel²,

Shuman³

et al. 2004

J Virol

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The paramyxovirus family includes many well-known human and animal pathogens as well as emerging viruses such as Hendra virus and Nipah virus. The V protein of simian virus 5 (SV5), a prototype of the paramyxoviruses, contains a cysteine-rich C-terminal domain which is conserved among all paramyxovirus V proteins. The V protein can block both interferon (IFN) signaling by causing degradation of STAT1 and IFN production by blocking IRF-3 nuclear import. Previously, it was reported that recombinant SV5 lacking the C terminus of the V protein (rSV5V⌬C) induces a severe cytopathic effect (CPE) in tissue culture whereas wild-type (wt) SV5 infection does not induce CPE. In this study, the nature of the CPE and the mechanism of the induction of CPE were investigated. Through the use of DNA fragmentation, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling, and propidium iodide staining assays, it was shown that rSV5V⌬C induced apoptosis. Expression of wt V protein prevented apoptosis induced by rSV5V⌬C, suggesting that the V protein has an antiapoptotic function. Interestingly, rSV5V⌬C induced apoptosis in U3A cells (a STAT1-deficient cell line) and in the presence of neutralizing antibody against IFN, suggesting that the induction of apoptosis by rSV5V⌬C was independent of IFN and IFN-signaling pathways. Apoptosis induced by rSV5V⌬C was blocked by a general caspase inhibitor, Z-VAD-FMK, but not by specific inhibitors against caspases 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 13, suggesting that rSV5V⌬C-induced apoptosis can occur in a caspase 12-dependent manner. Endoplasmic reticulum stress can lead to activation of caspase 12; compared to the results seen with mock and wt SV5 infection, rSV5V⌬C infection induced ER stress, as demonstrated by increased expression levels of known ER stress indicators GRP 78, GRP 94, and GADD153. These data suggest that rSV5V⌬C can trigger cell death by inducing ER stress.

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Measles Virus V Protein Binds Zinc

Cited by 97 publications

References 0 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

Paramyxovirus evasion of innate immunity: Diverse strategies for common targets

Conserved Cysteine-Rich Domain of Paramyxovirus Simian Virus 5 V Protein Plays an Important Role in Blocking Apoptosis

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