SHUT_HHV11
ID SHUT_HHV11 Reviewed; 489 AA.
AC P10225; Q09I92; Q82170;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 95.
DE RecName: Full=Virion host shutoff protein;
DE Short=Vhs;
DE EC=3.1.27.-;
GN Name=UL41;
OS Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Alphaherpesvirinae; Simplexvirus.
OX NCBI_TaxID=10299;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2839594; DOI=10.1099/0022-1317-69-7-1531;
RA McGeoch D.J., Dalrymple M.A., Davison A.J., Dolan A., Frame M.C., McNab D.,
RA Perry L.J., Scott J.E., Taylor P.;
RT "The complete DNA sequence of the long unique region in the genome of
RT herpes simplex virus type 1.";
RL J. Gen. Virol. 69:1531-1574(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=HSZP;
RX PubMed=9421879; DOI=10.1023/a:1007915025086;
RA Vojvodova A., Matis J., Kudelova M., Rajcani J.;
RT "Herpes simplex virus type 1 (HSV-1) strain HSZP host shutoff gene:
RT nucleotide sequence and comparison with HSV-1 strains differing in early
RT shutoff of host protein synthesis.";
RL Virus Genes 15:155-159(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Nonneuroinvasive mutant HF10;
RA Nishiyama Y., Ushijima Y.;
RT "Sequence analysis of a nonneuroinvasive Herpes simplex virus type 1 mutant
RT HF10.";
RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION.
RC STRAIN=F;
RX PubMed=12072498; DOI=10.1128/jvi.76.14.6974-6986.2002;
RA Trgovcich J., Johnson D., Roizman B.;
RT "Cell surface major histocompatibility complex class II proteins are
RT regulated by the products of the gamma(1)34.5 and U(L)41 genes of herpes
RT simplex virus 1.";
RL J. Virol. 76:6974-6986(2002).
RN [5]
RP FUNCTION.
RX PubMed=16940547; DOI=10.1128/jvi.01008-06;
RA Taddeo B., Roizman B.;
RT "The virion host shutoff protein (UL41) of herpes simplex virus 1 is an
RT endoribonuclease with a substrate specificity similar to that of RNase A.";
RL J. Virol. 80:9341-9345(2006).
RN [6]
RP FUNCTION.
RX PubMed=17093196; DOI=10.1128/jvi.01812-06;
RA Read G.S., Patterson M.;
RT "Packaging of the virion host shutoff (Vhs) protein of herpes simplex
RT virus: two forms of the Vhs polypeptide are associated with intranuclear B
RT and C capsids, but only one is associated with enveloped virions.";
RL J. Virol. 81:1148-1161(2007).
RN [7]
RP FUNCTION.
RX PubMed=20357089; DOI=10.1128/jvi.01819-09;
RA Saffran H.A., Read G.S., Smiley J.R.;
RT "Evidence for translational regulation by the herpes simplex virus virion
RT host shutoff protein.";
RL J. Virol. 84:6041-6049(2010).
RN [8]
RP FUNCTION, AND INTERACTION WITH EIF4H AND EIF4A1.
RX PubMed=20427534; DOI=10.1128/jvi.00166-10;
RA Page H.G., Read G.S.;
RT "The virion host shutoff endonuclease (UL41) of herpes simplex virus
RT interacts with the cellular cap-binding complex eIF4F.";
RL J. Virol. 84:6886-6890(2010).
RN [9]
RP FUNCTION.
RX PubMed=23077305; DOI=10.1128/jvi.01557-12;
RA Shiflett L.A., Read G.S.;
RT "mRNA decay during herpes simplex virus (HSV) infections: mutations that
RT affect translation of an mRNA influence the sites at which it is cleaved by
RT the HSV virion host shutoff (Vhs) protein.";
RL J. Virol. 87:94-109(2013).
RN [10]
RP FUNCTION.
RX PubMed=27681138; DOI=10.1128/jvi.01672-16;
RA Jiang Z., Su C., Zheng C.;
RT "Herpes simplex virus 1 tegument protein UL41 counteracts IFIT3 antiviral
RT innate immunity.";
RL J. Virol. 90:11056-11061(2016).
RN [11]
RP FUNCTION.
RX PubMed=28404225; DOI=10.1016/j.antiviral.2017.04.004;
RA You H., Yuan H., Fu W., Su C., Wang W., Cheng T., Zheng C.;
RT "Herpes simplex virus type 1 abrogates the antiviral activity of Ch25h via
RT its virion host shutoff protein.";
RL Antiviral Res. 143:69-73(2017).
RN [12]
RP FUNCTION.
RX PubMed=28077645; DOI=10.1128/jvi.02414-16;
RA Su C., Zheng C.;
RT "Herpes simplex virus 1 abrogates the cGAS/STING-mediated Cytosolic DNA-
RT Sensing Pathway via its virion host shutoff protein, UL41.";
RL J. Virol. 91:0-0(2017).
CC -!- FUNCTION: Minor structural protein that acts as an endoribonuclease
CC during lytic infection. Degrades host mRNAs in the cytoplasm by cutting
CC them at preferred sites, including some in regions of translation
CC initiation. Together with inhibition of host splicing by ICP27,
CC contributes to an overall decrease in host protein synthesis. Also,
CC after the onset of viral transcription, accelerates the turnover of
CC viral mRNA, thereby facilitating the sequential expression of different
CC classes of viral genes. Binds translation initiation factors eIF4H,
CC eIF4AI, and eIF4AII, thereby may interact directly with the translation
CC initiation complex and thus digest specifically mRNAs. Also impedes
CC antigen presentation by major histocompatibility complex class I and
CC class II molecules, inhibits secretion of cytokines that would
CC otherwise recruit lymphocytes and neutrophils cells to the site of
CC infection and blocks the activation of dendritic cells. Plays a role in
CC the inhibition of interferon-beta activation by the cGAS/STING pathway.
CC Mechanistically, down-regulates the expression of host cGAS/MB21D1.
CC Decreases also the accumulation of other interferon-induced mRNAs such
CC as host IFIT3 or CH25H to subvert their antiviral activity.
CC {ECO:0000269|PubMed:12072498, ECO:0000269|PubMed:16940547,
CC ECO:0000269|PubMed:17093196, ECO:0000269|PubMed:20357089,
CC ECO:0000269|PubMed:20427534, ECO:0000269|PubMed:23077305,
CC ECO:0000269|PubMed:27681138, ECO:0000269|PubMed:28077645,
CC ECO:0000269|PubMed:28404225}.
CC -!- SUBUNIT: Interacts with human EIF4H, EIF4A1 and EIF4A2; interaction
CC with eIF4AI and EIF4A2 presumably allows Vhs protein to associate with
CC the eIF4F cap-binding complex. {ECO:0000305|PubMed:20427534}.
CC -!- INTERACTION:
CC P10225; P06492: UL48; NbExp=3; IntAct=EBI-6148417, EBI-7489933;
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000305}.
CC -!- MISCELLANEOUS: Strain 17 is relatively weak regarding early shutoff
CC compared to strain KOS. Strain HSZP protein is non-functional for host
CC protein shutoff.
CC -!- SIMILARITY: Belongs to the herpesviridae VHS protein family.
CC {ECO:0000305}.
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DR EMBL; X14112; CAA32304.1; -; Genomic_DNA.
DR EMBL; DQ889502; ABI63503.1; -; Genomic_DNA.
DR EMBL; Z72337; CAA96524.1; -; Genomic_DNA.
DR PIR; E30088; WMBEF1.
DR BioGRID; 971408; 1.
DR DIP; DIP-57855N; -.
DR IntAct; P10225; 8.
DR PRIDE; P10225; -.
DR Proteomes; UP000009294; Genome.
DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0039595; P:induction by virus of catabolism of host mRNA; IEA:UniProtKB-KW.
DR GO; GO:0039657; P:suppression by virus of host gene expression; IEA:UniProtKB-KW.
DR InterPro; IPR029060; PIN-like_dom_sf.
DR InterPro; IPR006086; XPG-I_dom.
DR Pfam; PF00867; XPG_I; 1.
DR SUPFAM; SSF88723; SSF88723; 1.
PE 1: Evidence at protein level;
KW Decay of host mRNAs by virus; Endonuclease;
KW Eukaryotic host gene expression shutoff by virus;
KW Host gene expression shutoff by virus; Host mRNA suppression by virus;
KW Host-virus interaction; Hydrolase; Interferon antiviral system evasion;
KW Late protein; Nuclease; Reference proteome; RNA-binding;
KW Viral immunoevasion; Virion.
FT CHAIN 1..489
FT /note="Virion host shutoff protein"
FT /id="PRO_0000116054"
FT REGION 110..135
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 142..161
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 285..319
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 332..364
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 18
FT /note="R -> H (in strain: HSZP)"
FT VARIANT 115
FT /note="V -> A (in strain: HSZP)"
FT VARIANT 316
FT /note="E -> K (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 364
FT /note="P -> S (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 374
FT /note="L -> R (in strain: HSZP)"
FT VARIANT 384..386
FT /note="NPR -> SRQ (in strain: HSZP)"
FT VARIANT 385
FT /note="P -> R (in strain: Nonneuroinvasive mutant HF10)"
FT VARIANT 392
FT /note="D -> N (in strain: HSZP)"
FT VARIANT 452
FT /note="V -> M (in strain: HSZP)"
SQ SEQUENCE 489 AA; 54918 MW; 3DD706B26A1873BD CRC64;
MGLFGMMKFA HTHHLVKRRG LGAPAGYFTP IAVDLWNVMY TLVVKYQRRY PSYDREAITL
HCLCRLLKVF TQKSLFPIFV TDRGVNCMEP VVFGAKAILA RTTAQCRTDE EASDVDASPP
PSPITDSRPS SAFSNMRRRG TSLASGTRGT AGSGAALPSA APSKPALRLA HLFCIRVLRA
LGYAYINSGQ LEADDACANL YHTNTVAYVY TTDTDLLLMG CDIVLDISAC YIPTINCRDI
LKYFKMSYPQ FLALFVRCHT DLHPNNTYAS VEDVLRECHW TPPSRSQTRR AIRREHTSSR
STETRPPLPP AAGGTETRVS WTEILTQQIA GGYEDDEDLP LDPRDVTGGH PGPRSSSSEI
LTPPELVQVP NAQLLEEHRS YVANPRRHVI HDAPESLDWL PDPMTITELV EHRYIKYVIS
LIGPKERGPW TLLKRLPIYQ DIRDENLARS IVTRHITAPD IADRFLEQLR TQAPPPAFYK
DVLAKFWDE
