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 27-MAR-2024, entry version 101. 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; Orthoherpesviridae; Alphaherpesvirinae; Simplexvirus; OC Simplexvirus humanalpha1; Human herpesvirus 1. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 Proteomes; UP000009294; Genome. DR GO; GO:0044423; C:virion component; IEA:UniProtKB-KW. 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 GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-KW. DR Gene3D; 3.40.50.1010; 5'-nuclease; 1. DR InterPro; IPR029060; PIN-like_dom_sf. DR InterPro; IPR006086; XPG-I_dom. DR Pfam; PF00867; XPG_I; 1. DR SUPFAM; SSF88723; PIN domain-like; 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; KW Inhibition of host innate immune response by virus; KW Interferon antiviral system evasion; Late protein; Nuclease; KW Reference proteome; RNA-binding; 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 //