The V protein of the paramyxovirus Nipah virus (NiV) has been shown to antagonize the interferon (IFN) response in human cells via sequestration of STAT1 and STAT2. This study describes a mutant of the NiV V protein, referred to as V(AAHL), that is unable to antagonize IFN signalling and demonstrates that a single amino acid substitution is responsible for its inactivity. The molecular basis for this was identified as a failure to interact with STAT1 and STAT2. It was also shown that NiV V, but not V(AAHL), was functional as an IFN antagonist in human, monkey, rabbit, dog, horse, pig and bat cells, which suggests that the ability of NiV to block IFN signalling is not a major constraint that prevents this virus from crossing species barriers.
AbuBakarS.,
ChangL.-Y.,
AliA. R. M.,
SharifahS. H.,
YusoffK.,
ZamrodZ.2004; Isolation and molecular identification of Nipah virus from pigs. Emerg Infect Dis 10:2228–2230[CrossRef]
ChatziandreouN.,
YoungD.,
AndrejevaJ.,
GoodbournS.,
RandallR. E.2002; Differences in interferon sensitivity and biological properties of two related isolates of simian virus 5: a model for virus persistence. Virology 293:234–242[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
GarcinD.,
MarqJ.-B.,
StrahleL.,
le MercierP.,
KolakofskyD.2002; All four Sendai virus C proteins bind Stat1, but only the larger forms also induce its mono-ubiquitination and degradation. Virology 295:256–265[CrossRef]
HalpinK.,
YoungP. L.,
FieldH. E.,
MackenzieJ. S.2000; Isolation of Hendra virus from pteropid bats: a natural reservoir of Hendra virus. J Gen Virol 81:1927–1932
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- β induction and interferon signaling. Virology 303:15–32[CrossRef]
HooperP.,
ZakiS.,
DanielsP.,
MiddletonD.2001; Comparative pathology of the diseases caused by Hendra and Nipah viruses. Microbes Infect 3:315–322[CrossRef]
LambR. A.,
KolakofskyD.2001; Paramyxoviridae : the viruses and their replication. In Fields Virology , 4th edn. pp 1305–1340 Edited by
KnipeD. M.,
HowleyP. M.
Philadelphia: Lippincott Williams & Wilkins;
MiddletonD. J.,
WestburyH. A.,
MorrissyC. J.,
van der HeideB. M.,
RussellG. M.,
BraunM. A.,
HyattA. D.2002; Experimental Nipah virus infection in pigs and cats. J Comp Pathol 126:124–136[CrossRef]
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. Curr Top Microbiol Immunol 283:197–248
O'SullivanJ. D.,
AllworthA. M.,
PatersonD. L.,
SnowT. M.,
BootsR.,
GleesonL. J.,
GouldA. R.,
HyattA. D.,
BradfieldJ.1997; Fatal encephalitis due to novel paramyxovirus transmitted from horses. Lancet 349:93–95[CrossRef]
ParkM.-S.,
ShawM. L.,
Muñoz-JordanJ.,
CrosJ. F.,
NakayaT.,
BouvierN.,
PaleseP.,
García-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]
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.,
García-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]
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.
Dordecht: Springer;
WangL.-F.,
YuM.,
HanssonE.,
PritchardL. I.,
ShiellB.,
MichalskiW. P.,
EatonB. T.2000; The exceptionally large genome of Hendra virus: support for creation of a new genus within the family Paramyxoviridae
. J Virol 74:9972–9979[CrossRef]
WongK. T.,
GrosjeanI.,
BrissonC.& 11 other authors2003; A golden hamster model for human acute Nipah virus infection. Am J Pathol 163:2127–2137[CrossRef]
YobJ. M.,
FieldH.,
RashdiA. M.& 8 other authors2001; Nipah virus infection in bats (order Chiroptera) in peninsular Malaysia. Emerg Infect Dis 7:439–441[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]