NSS_HTRV
ID NSS_HTRV Reviewed; 299 AA.
AC J3TRC5;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2012, sequence version 1.
DT 03-AUG-2022, entry version 18.
DE RecName: Full=Non-structural protein NS-S;
DE Short=NSs;
GN Name=NSS;
OS Heartland virus (HTRV).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Ellioviricetes; Bunyavirales; Phenuiviridae; Bandavirus;
OC Heartland bandavirus.
OX NCBI_TaxID=1216928;
OH NCBI_TaxID=999462; Alces americanus (American moose).
OH NCBI_TaxID=6943; Amblyomma americanum (Lone star tick).
OH NCBI_TaxID=9614; Canis latrans (Coyote).
OH NCBI_TaxID=9267; Didelphis virginiana (North American opossum) (Didelphis marsupialis virginiana).
OH NCBI_TaxID=9796; Equus caballus (Horse).
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9874; Odocoileus virginianus (White-tailed deer).
OH NCBI_TaxID=9654; Procyon lotor (Raccoon).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Isolate Human/United States/1/2009, and
RC Isolate Human/United States/2/2009;
RA McMullan L.K., Folk S.M., Kelly A.J., MacNeil A., Goldsmith C.S.,
RA Metcalfe M.G., Batten B.C., Albarino C.G., Zaki S.R., Rollin P.E.,
RA Nicholson W.L., Nichol S.T.;
RT "A newly discovered phlebovirus associated with severe febrile illness
RT following tick bite in two patients in Missouri.";
RL N. Engl. J. Med. 367:834-841(2012).
RN [2]
RP FUNCTION, AND INTERACTION WITH HOST TBK1.
RX PubMed=28848048; DOI=10.1074/jbc.m117.805127;
RA Ning Y.J., Feng K., Min Y.Q., Deng F., Hu Z., Wang H.;
RT "Heartland virus NSs protein disrupts host defenses by blocking the TBK1
RT kinase-IRF3 transcription factor interaction and signaling required for
RT interferon induction.";
RL J. Biol. Chem. 292:16722-16733(2017).
RN [3]
RP FUNCTION, INTERACTION WITH HOST TBK1, AND SUBCELLULAR LOCATION.
RX PubMed=28680969; DOI=10.1128/msphere.00234-17;
RA Rezelj V.V., Li P., Chaudhary V., Elliott R.M., Jin D.Y., Brennan B.;
RT "Differential Antagonism of Human Innate Immune Responses by Tick-Borne
RT Phlebovirus Nonstructural Proteins.";
RL MSphere 2:0-0(2017).
RN [4]
RP INTERACTION WITH HOST TBK1, AND MUTAGENESIS OF 21-VAL--LEU-23;
RP 24-VAL--LEU-26; 27-VAL--LEU-29 AND 66-PRO--PRO-69.
RX PubMed=30021900; DOI=10.1128/jvi.00706-18;
RA Moriyama M., Igarashi M., Koshiba T., Irie T., Takada A., Ichinohe T.;
RT "Two Conserved Amino Acids within the NSs of Severe Fever with
RT Thrombocytopenia Syndrome Phlebovirus Are Essential for Anti-interferon
RT Activity.";
RL J. Virol. 92:0-0(2018).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH HOST STAT2.
RC STRAIN=MO-4 {ECO:0000305};
RX PubMed=31040183; DOI=10.1074/jbc.ra118.006563;
RA Feng K., Deng F., Hu Z., Wang H., Ning Y.J.;
RT "Heartland virus antagonizes type I and III interferon antiviral signaling
RT by inhibiting phosphorylation and nuclear translocation of STAT2 and
RT STAT1.";
RL J. Biol. Chem. 294:9503-9517(2019).
RN [6]
RP INTERACTION WITH HOST TNIP2.
RX PubMed=30617349; DOI=10.1038/s41564-018-0329-x;
RA Choi Y., Park S.J., Sun Y., Yoo J.S., Pudupakam R.S., Foo S.S., Shin W.J.,
RA Chen S.B., Tsichlis P.N., Lee W.J., Lee J.S., Li W., Brennan B., Choi Y.K.,
RA Jung J.U.;
RT "Severe fever with thrombocytopenia syndrome phlebovirus non-structural
RT protein activates TPL2 signalling pathway for viral immunopathogenesis.";
RL Nat. Microbiol. 4:429-437(2019).
CC -!- FUNCTION: Plays a role in the inhibition of host RLR-induced
CC interferon-beta activation by inhibiting the phosphorylation of TANK-
CC binding kinase 1/TBK1, thereby blocking IRF3 activation and preventing
CC the establishment of an antiviral state (PubMed:28848048,
CC PubMed:28680969). Also blocks IFN-triggered nuclear translocation and
CC activation of host STAT2 (PubMed:31040183, PubMed:28680969).
CC {ECO:0000269|PubMed:28680969, ECO:0000269|PubMed:28848048,
CC ECO:0000269|PubMed:31040183}.
CC -!- SUBUNIT: Interacts with host TBK1; this interaction antagonizes TBK1
CC phosphorylation and inhibits TBK1-IRF3 interaction (PubMed:28848048,
CC PubMed:28680969) (Probable). Interacts with host STAT2; this
CC interaction blocks the nuclear translocation and activation of host
CC STAT2 (PubMed:31040183). Interacts with host TNIP2 (PubMed:30617349).
CC {ECO:0000269|PubMed:28680969, ECO:0000269|PubMed:28848048,
CC ECO:0000269|PubMed:30617349, ECO:0000269|PubMed:31040183,
CC ECO:0000305|PubMed:30021900}.
CC -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000269|PubMed:28680969,
CC ECO:0000269|PubMed:31040183}.
CC -!- SIMILARITY: Belongs to the Bandavirus NS-S protein family.
CC {ECO:0000305}.
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DR EMBL; JX005842; AFP33390.1; -; Genomic_RNA.
DR RefSeq; YP_009047243.1; NC_024496.1.
DR GeneID; 19893503; -.
DR KEGG; vg:19893503; -.
DR Proteomes; UP000203778; Genome.
DR InterPro; IPR039434; NSs-like.
DR Pfam; PF11073; NSs; 1.
PE 1: Evidence at protein level;
KW Host cytoplasm; Host-virus interaction;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus;
KW Inhibition of host IRF3 by virus; Inhibition of host RLR pathway by virus;
KW Inhibition of host STAT2 by virus; Inhibition of host TBK1 by virus;
KW Inhibition of host TLR pathway by virus; Viral immunoevasion.
FT CHAIN 1..299
FT /note="Non-structural protein NS-S"
FT /id="PRO_0000456168"
FT REGION 66..69
FT /note="Involved in inclusion bodies formation"
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC19"
FT REGION 148..220
FT /note="Interaction with host TNIP2"
FT /evidence="ECO:0000250|UniProtKB:A0A0B5AC19"
FT SITE 21
FT /note="Essential for suppression of TBK1/IRF3-mediated IFN
FT response"
FT /evidence="ECO:0000269|PubMed:30021900"
FT SITE 23
FT /note="Essential for suppression of TBK1/IRF3-mediated IFN
FT response"
FT /evidence="ECO:0000269|PubMed:30021900"
FT MUTAGEN 21..23
FT /note="VVL->AVA: 50% loss of the inhibition of IFN-beta
FT activation and loss of interaction with host TBK1."
FT /evidence="ECO:0000269|PubMed:30021900"
FT MUTAGEN 24..26
FT /note="EPN->APA: Almost complete loss of the inhibition of
FT IFN-beta activation and interaction with host TBK1."
FT /evidence="ECO:0000269|PubMed:30021900"
FT MUTAGEN 27..29
FT /note="LAE->AAA: No effect on the inhibition of IFN-beta
FT promoter activity."
FT /evidence="ECO:0000269|PubMed:30021900"
FT MUTAGEN 66..69
FT /note="PNNP->ANNA: Almost complete loss of the inhibition
FT of IFN-beta activation."
FT /evidence="ECO:0000269|PubMed:30021900"
SQ SEQUENCE 299 AA; 34006 MW; 1C12BB38CD48A1C9 CRC64;
MSLSKASQPS VKSACVRLPI VVLEPNLAEL STSYVGLVSC KCSVLTCSMM RKMKAFTNTV
WLFGNPNNPL HALEPAVEQL LDEYSGDLGS YSQQEKSALR WPSGKPSVHF LQAAHLFFSL
KNTWAVETGQ ENWRGFFHRI TSGKKYKFEG DMVIDSCYKI DERRRRMGLP DTFITGLNPI
MDVALLQIES LLRVRGLTLN YHLFTSSFLD KPLLDSLYFA IWRDKKKDDG SYSQDEGARQ
DDPLNPLDEL LYLSDLPKPL AHYLNKCPLH NIIMHDEEVR EAYLNPIWGK DWPALSSSP
