Mapuera virus (MPRV) is a paramyxovirus that was originally isolated from bats, but its host range remains unknown. It was classified as a member of the genus Rubulavirus on the basis of structural and genetic features. Like other rubulaviruses it encodes a V protein (MPRV/V) that functions as an interferon (IFN) antagonist. Here we show that MPRV/V differs from the IFN antagonists of other rubulaviruses in that it does not induce the proteasomal degradation of STAT proteins, key factors in the IFN signalling cascade. Rather, MPRV/V prevents the nuclear translocation of STATs in response to IFN stimulation and inhibits the formation of the transcription factor complex ISGF3. We also show that MPRV/V blocks IFN signalling in cells from diverse mammalian species and discuss the IFN response as a barrier to cross-species infections.
AndrejevaJ.,
PooleE.,
YoungD. F.,
GoodbournS.,
RandallR. E.2002a; The p127 subunit (DDB1) of the UV-DNA damage repair binding protein is essential for the targeted degradation of STAT1 by the V protein of the paramyxovirus simian virus 5. J Virol 76:11379–11386[CrossRef]
AndrejevaJ.,
YoungD. F.,
GoodbournS.,
RandallR. E.2002b; Degradation of STAT1 and STAT2 by the V proteins of simian virus 5 and human parainfluenza virus type 2, respectively: consequences for virus replication in the presence of alpha/beta and gamma interferons. J Virol 76:2159–2167[CrossRef]
AndrejevaJ.,
ChildsK. S.,
YoungD. F.,
CarlosT. S.,
StockN.,
GoodbournS.,
RandallR. E.2004; The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN- β promoter. Proc Natl Acad Sci U S A 101:17264–17269[CrossRef]
BossertB.,
ConzelmannK. K.2002; Respiratory syncytial virus (RSV) nonstructural (NS) proteins as host range determinants: a chimeric bovine RSV with NS genes from human RSV is attenuated in interferon-competent bovine cells. J Virol 76:4287–4293[CrossRef]
ChildsK.,
StockN.,
RossC.,
AndrejevaJ.,
HiltonL.,
SkinnerM.,
RandallR.,
GoodbournS.2006; mda-5, but not RIG-I, is a common target for paramyxovirus V proteins. Virology. (in press). doi: 10.1016/j.virol.2006.09.023
ChoppinP. W.1964; Multiplication of a myxovirus (Sv5) with minimal cytopathic effects and without interference. Virology 23:224–233[CrossRef]
DidcockL.,
YoungD. F.,
GoodbournS.,
RandallR. E.1999; The V protein of simian virus 5 inhibits interferon signalling by targeting STAT1 for proteasome-mediated degradation. J Virol 73:9928–9933
Garcia-SastreA.2004; Identification and characterisation of viral antagonists of type 1 interferon in negative-strand RNA viruses. In Biology of Negative Strand RNA Viruses pp 249–280 Edited by
KawaokaY.
Berlin/Heidelberg/New York: Springer-Verlag;
HagmaierK.,
StockS.,
GoodbournS.,
WangL.-F.,
RandallR. E.2006; A single amino acid substitution in the V protein of Nipah virus alters its ability to block interferon signalling in cells from different species. J Gen Virol 87:3649–3653[CrossRef]
HeB.,
PatersonR. G.,
StockN.,
DurbinJ. E.,
DurbinR. K.,
GoodbournS.,
RandallR. E.,
LambR. A.2002; Recovery of paramyxovirus simian virus 5 with a V protein lacking the conserved cysteine-rich domain: the multifunctional V protein blocks both interferon-beta induction and interferon signaling. Virology 303:15–32[CrossRef]
HendersonG. W.,
LairdC.,
DermottE.,
RimaB. K.1995; Characterization of Mapuera virus: structure, proteins and nucleotide sequence of the gene encoding the nucleocapsid protein. J Gen Virol 76:2509–2518[CrossRef]
KatoH.,
TakeuchiO.,
SatoS.,
YoneyamaM.,
YamamotoM.,
MatsuiK.,
UematsuS.,
JungA.,
KawaiT.other authors2006; Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 441:101–105[CrossRef]
KubotaT.,
YokosawaN.,
YokotaS.,
FujiiN.,
TashiroM.,
KatoA.2005; Mumps virus V protein antagonizes interferon without the complete degradation of STAT1. J Virol 79:4451–4459[CrossRef]
LiT.,
ChenX.,
GarbuttK. C.,
ZhouP.,
ZhengN.2006; Structure of DDB1 in complex with a paramyxovirus V protein: viral hijack of a propeller cluster in ubiquitin ligase. Cell 124:105–117[CrossRef]
LinG. Y.,
PatersonR. G.,
RichardsonC. D.,
LambR. A.1998; The V protein of the paramyxovirus SV5 interacts with damage-specific DNA binding protein. Virology 249:189–200[CrossRef]
MassonN.,
EllisM.,
GoodbournS.,
LeeK. A.1992; Cyclic AMP response element-binding protein and the catalytic subunit of protein kinase A are present in F9 embryonal carcinoma cells but are unable to activate the somatostatin promoter. Mol Cell Biol 12:1096–1106
NagaiY.,
KatoA.2004; Accessory genes of the Paramyxoviridae, a large family of nonsegmented negative-strand RNA viruses, as a focus of active investigation by reverse genetics. In Biology of Negative Strand RNA Viruses pp 197–248 Edited by
KawaokaY.
Berlin/Heidelberg/New York: Springer-Verlag;
NishioM.,
TsurudomeM.,
ItoM.,
ItoY.2005; Human parainfluenza virus type 4 is incapable of evading the interferon-induced antiviral effect. J Virol 79:14756–14768[CrossRef]
OhnoS.,
OnoN.,
TakedaM.,
TakeuchiK.,
YanagiY.2004; Dissection of measles virus V protein in relation to its ability to block alpha/beta interferon signal transduction. J Gen Virol 85:2991–2999[CrossRef]
PalosaariH.,
ParisienJ. P.,
RodriguezJ. J.,
UlaneC. M.,
HorvathC. M.2003; STAT protein interference and suppression of cytokine signal transduction by measles virus V protein. J Virol 77:7635–7644[CrossRef]
ParisienJ. P.,
LauJ. F.,
RodriguezJ. J.,
SullivanB. M.,
MosconaA.,
ParksG. D.,
LambR. A.,
HorvathC. M.2001; The V protein of human parainfluenza virus 2 antagonizes type I interferon responses by destabilizing signal transducer and activator of transcription 2. Virology 283:230–239[CrossRef]
ParisienJ. P.,
LauJ. F.,
RodriguezJ. J.,
UlaneC. M.,
HorvathC. M.2002b; Selective STAT protein degradation induced by paramyxoviruses requires both STAT1 and STAT2 but is independent of alpha/beta interferon signal transduction. J Virol 76:4190–4198[CrossRef]
ParkM. S.,
ShawM. L.,
Munoz-JordanJ.,
CrosJ. F.,
NakayaT.,
BouvierN.,
PaleseP.,
Garcia-SastreA.,
BaslerC. F.2003; Newcastle disease virus (NDV)-based assay demonstrates interferon-antagonist activity for the NDV V protein and the Nipah virus V, W, and C proteins. J Virol 77:1501–1511[CrossRef]
PatersonR. G.,
LeserG. P.,
ShaughnessyM. A.,
LambR. A.1995; The paramyxovirus SV5 V protein binds two atoms of zinc and is a structural component of virions. Virology 208:121–131[CrossRef]
PooleE.,
HeB.,
LambR. A.,
RandallR. E.,
GoodbournS.2002; The V proteins of simian virus 5 and other paramyxoviruses inhibit induction of interferon-beta. Virology 303:33–46[CrossRef]
PreciousB.,
ChildsK.,
Fitzpatrick-SwallowV.,
GoodbournS.,
RandallR. E.2005a; Simian virus 5 V protein acts as an adaptor, linking DDB1 to STAT2, to facilitate the ubiquitination of STAT1. J Virol 79:13434–13441[CrossRef]
PreciousB.,
YoungD. F.,
AndrejevaL.,
GoodbournS.,
RandallR. E.2005b; In vitro and in vivo specificity of ubiquitination and degradation of STAT1 and STAT2 by the V proteins of the paramyxoviruses simian virus 5 and human parainfluenza virus type 2. J Gen Virol 86:151–158[CrossRef]
RandallR. E.,
DinwoodieN.1986; Intranuclear localization of herpes simplex virus immediate-early and delayed-early proteins: evidence that ICP 4 is associated with progeny virus DNA. J Gen Virol 67:2163–2177[CrossRef]
RodriguezJ. J.,
ParisienJ. P.,
HorvathC. M.2002; Nipah virus V protein evades alpha and gamma interferons by preventing STAT1 and STAT2 activation and nuclear accumulation. J Virol 76:11476–11483[CrossRef]
RodriguezJ. J.,
CruzC. D.,
HorvathC. M.2004; Identification of the nuclear export signal and STAT-binding domains of the Nipah virus V protein reveals mechanisms underlying interferon evasion. J Virol 78:5358–5367[CrossRef]
ShawM. L.,
Garcia-SastreA.,
PaleseP.,
BaslerC. F.2004; Nipah virus V and W proteins have a common STAT1-binding domain yet inhibit STAT1 activation from the cytoplasmic and nuclear compartments, respectively. J Virol 78:5633–5641[CrossRef]
ShuaiK.,
ZiemieckiA.,
WilksA. F.,
HarpurA. G.,
SadowskiH. B.,
GilmanM. Z.,
DarnellJ. E.1993; Polypeptide signalling to the nucleus through tyrosine phosphorylation of Jak and Stat proteins. Nature 366:580–583[CrossRef]
StockN.,
GoodbournS.,
RandallR. E.2005; The anti-interferon mechanisms of paramyxoviruses. In Modulation of Host Gene Expression and Innate Immunity in Viruses pp 115–140 Edited by
PaleseP.,
ChangeuxJ.-P.
Dordrecht: Springer;
TakeuchiK.,
KadotaS. I.,
TakedaM.,
MiyajimaN.,
NagataK.2003; Measles virus V protein blocks interferon (IFN)-alpha/beta but not IFN-gamma signaling by inhibiting STAT1 and STAT2 phosphorylation. FEBS Lett 545:177–182[CrossRef]
ThomasS. M.,
LambR. A.,
PatersonR. G.1988; Two mRNAs that differ by two nontemplated nucleotides encode the amino coterminal proteins P and V of the paramyxovirus SV5. Cell 54:891–902[CrossRef]
UlaneC. M.,
HorvathC. M.2002; Paramyxoviruses SV5 and HPIV2 assemble STAT protein ubiquitin ligase complexes from cellular components. Virology 304:160–166[CrossRef]
UlaneC. M.,
KentsisA.,
CruzC. D.,
ParisienJ. P.,
SchneiderK. L.,
HorvathC. M.2005; Composition and assembly of STAT-targeting ubiquitin ligase complexes: paramyxovirus V protein carboxyl terminus is an oligomerization domain. J Virol 79:10180–10189[CrossRef]
WansleyE. K.,
ParksG. D.2002; Naturally occurring substitutions in the P/V gene convert the noncytopathic paramyxovirus simian virus 5 into a virus that induces alpha/beta interferon synthesis and cell death. J Virol 76:10109–10121[CrossRef]
YokosawaN.,
YokotaS.,
KubotaT.,
FujiiN.2002; C-terminal region of STAT-1alpha is not necessary for its ubiquitination and degradation caused by mumps virus V protein. J Virol 76:12683–12690[CrossRef]
YokotaS.,
SaitoH.,
KubotaT.,
YokosawaN.,
AmanoK.,
FujiiN.2003; Measles virus suppresses interferon-alpha signaling pathway: suppression of Jak1 phosphorylation and association of viral accessory proteins, C and V, with interferon-alpha receptor complex. Virology 306:135–146[CrossRef]
YoungD. F.,
ChatziandreouN.,
HeB.,
GoodbournS.,
LambR. A.,
RandallR. E.2001; Single amino acid substitution in the V protein of simian virus 5 differentiates its ability to block interferon signaling in human and murine cells. J Virol 75:3363–3370[CrossRef]
YoungD. F.,
AndrejevaL.,
LivingstoneA.,
GoodbournS.,
LambR. A.,
CollinsP. L.,
ElliottR. M.,
RandallR. E.2003; Virus replication in engineered human cells that do not respond to interferons. J Virol 77:2174–2181[CrossRef]
ZellerH. G.,
KarabatsosN.,
CalisherC. H.,
DigoutteJ. P.,
MurphyF. A.,
ShopeR. E.1989; Electron microscopy and antigenic studies of uncharacterized viruses. I. Evidence suggesting the placement of viruses in families Arenaviridae, Paramyxoviridae, or Poxviridae. Arch Virol 108:191–209[CrossRef]