ID   SHUT_HHV23              Reviewed;         492 AA.
AC   O39988;
DT   03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   03-AUG-2022, entry version 71.
DE   RecName: Full=Virion host shutoff protein;
DE            Short=Vhs;
DE            EC=3.1.27.-;
GN   Name=UL41;
OS   Human herpesvirus 2 (strain 333) (HHV-2) (Human herpes simplex virus 2).
OC   Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC   Herpesvirales; Herpesviridae; Alphaherpesvirinae; Simplexvirus.
OX   NCBI_TaxID=10313;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=9311788; DOI=10.1128/jvi.71.10.7157-7166.1997;
RA   Everly D.N. Jr., Read G.S.;
RT   "Mutational analysis of the virion host shutoff gene (UL41) of herpes
RT   simplex virus (HSV): characterization of HSV type 1 (HSV-1)/HSV-2
RT   chimeras.";
RL   J. Virol. 71:7157-7166(1997).
RN   [2]
RP   FUNCTION.
RX   PubMed=8621929;
RA   Tigges M.A., Leng S., Johnson D.C., Burke R.L.;
RT   "Human herpes simplex virus (HSV)-specific CD8+ CTL clones recognize HSV-2-
RT   infected fibroblasts after treatment with IFN-gamma or when virion host
RT   shutoff functions are disabled.";
RL   J. Immunol. 156:3901-3910(1996).
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. Impedes the
CC       alpha/beta interferon-mediated response to infection (By similarity).
CC       {ECO:0000250, ECO:0000269|PubMed:8621929}.
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:0000250}.
CC   -!- SUBCELLULAR LOCATION: Virion {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the herpesviridae VHS protein family.
CC       {ECO:0000305}.
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DR   EMBL; AF007816; AAC58447.1; -; Genomic_DNA.
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   3: Inferred from homology;
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; RNA-binding; Viral immunoevasion; Virion.
FT   CHAIN           1..492
FT                   /note="Virion host shutoff protein"
FT                   /id="PRO_0000283699"
FT   REGION          110..130
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          288..307
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          334..371
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   492 AA;  55343 MW;  0373259CF41F06C8 CRC64;
     MGLFGMMKFA QTHHLVKRRG LRAPEGYFTP IAVDLWNVMY TLVVKYQRRY PSYDREAITL
     HCLCSMLRVF TQKSLFPIFV TDRGVECTEP VVFGAKAILA RTTAQCRTDE EASDVDASPP
     PSPITDSRPS FAFSNMRRRG HAFAPGDRGT RAAGPGPAAP WGAPSKPALR LAHLFCIRVL
     RALGYAYINS GQLEADDACA NLYHTNTVAY VHTTDTDLLL MGCDIVLDIS TGYIPTIHCR
     DLLQYFKMSY PQFLALFVRC HTDLHPNNTY ASVEDVLREC HWTAPSRSQA RRAARRERAN
     SRSLESMPTL TAAPVGLETR ISWTEILAQQ IAGEDDYEED PPLQPPDVAG GPRDGARSSS
     SEILTPPELV QVPNAQRVAE HRGYVAGRRR HVIHDAPEAL DWLPDPMTIA ELVEHRYVKY
     VISLISPKER GPWTLLKRLP IYQDLRDEDL ARSIVTRHIT APDIADRFLA QLWAHAPPPA
     FYKDVLAKFW DE