Gene ID:HHVTW001
GenBank Locus Tag:
DNA Molecule Name:
1
GenBank ID:
132753
Gene Name:
gamma34.5 RL1
Definition:
anti-host defense factor, ICP34.5 (RL1_HSV2H)
Cellular Location:
[Evidence]
Gene Start:
440
Gene Stop:
1379
Gene Length:
940
Molecular Weight*:
27894
pI*:
11.90
Net Charge*:
19.83
EC:
Functional Class:
translation regulation
virulence factor; neurovirulence
Gene Ontology:
Pathway: pathway table
Primary Evidence:
Ravi V, Kennedy PG, MacLean AR, Functional analysis of the herpes simplex virus type 2 strain HG52 RL1 gene: the intron plays no role in virulence, J Gen Virol 1998 Jul;79 ( Pt 7):1613-7,
Medline: 98343716.
Suzutani T, The relationship between gene function and virulence in alpha-herpesviruses, Nippon Rinsho 2000 Apr;58(4):801-6, Medline: 10774198.
Harland JE, Bdour S, Brown SM, MacLean AR, The herpes simplex virus type 2 strain HG52 RL1 gene contains a 154 bp intron as
predicted from sequence analysis, J Gen Virol 1996 Mar;77 ( Pt 3):481-4, Medline: 96177330.
McGeoch,D.J., Cunningham,C., McIntyre,G. and Dolan,A., Comparative sequence analysis of the long repeat regions and adjoining parts of the long unique regions in the genomes of herpes simplex viruses types 1 and 2, J. Gen. Virol. 72 (Pt 12), 3057-3075 (1991), Medline: 92113549.
Secondary Evidence:
Trgovcich J, Johnson D, Roizman B., Cell surface major histocompatibility complex class II proteins are regulated by the products of the gamma(1)34.5 and U(L)41 genes of herpes simplex virus 1, J Virol. 2002 Jul;76(14):6974-86.
PMID: 12072498.
Poppers J, Mulvey M, Khoo D, Mohr I., Inhibition of PKR activation by the proline-rich RNA binding domain of the herpes simplex virus type 1 Us11 protein, J Virol 2000 Dec;74(23):11215-21, Medline: 11070019.
Howard MK, Kershaw T, Gibb B, Storey N, MacLean AR, Zeng BY, Tel BC, Jenner P, Brown SM, Woolf CJ, Anderson PN, Coffin RS, Latchman DS, High efficiency gene transfer to the central nervous system of rodents and primates using herpes virus vectors lacking functional ICP27 and ICP34.5, Gene Ther 1998 Aug;5(8):1137-47, Medline: 99257888.
Bower JR, Mao H, Durishin C, Rozenbom E, Detwiler M, Rempinski
D, Karban TL, Rosenthal KS, Intrastrain variants of herpes simplex virus type 1 isolated from a neonate with fatal disseminated infection differ in the ICP34.5 gene, glycoprotein processing, and neuroinvasiveness, J Virol 1999 May;73(5):3843-53, Medline: 99214322.
Cassady KA, Gross M, Roizman B, The second-site mutation in the herpes simplex virus recombinants lacking the gamma134.5 genes precludes shutoff protein synthesis by blocking the phosphorylation of eIF-2alpha, J Virol 1998 Sep;72(9):7005-11, Medline: 98362101.
Martin DW, Weber PC, Role of the DR2 repeat array in the regulation of the ICP34.5 gene promoter of herpes simplex virus type 1 during productive infection, J Gen Virol 1998 Mar;79 ( Pt 3):517-23, Medline: 98178645.
Brown SM, MacLean AR, McKie EA, Harland J, The herpes simplex virus virulence factor ICP34.5 and the cellular protein MyD116 complex with proliferating cell nuclear antigen through the 63-amino-acid domain conserved in ICP34.5, MyD116, and GADD34, J Virol 1997 Dec;71(12):9442-9, Medline: 98037656.
Perng GC, Chokephaibulkit K, Thompson RL, Sawtell NM, Slanina SM, Ghiasi H, Nesburn AB, Wechsler SL, The region of the herpes simplex virus type 1 LAT gene that is colinear with the ICP34.5 gene is not involved in spontaneous reactivation, J Virol 1996 Jan;70(1):282-91, Medline: 96099441.
Chou J, Chen JJ, Gross M, Roizman B, Association of a M(r) 90,000 phosphoprotein with protein kinase PKR in cells exhibiting enhanced phosphorylation of translation initiation factor eIF-2 alpha and premature shutoff of protein synthesis after infection with gamma 134.5- mutants of herpes simplex virus 1, Proc Natl Acad Sci U S A 1995 Nov 7;92(23):10516-20, Medline: 96068646.
Brown SM, MacLean AR, Aitken JD, Harland J,ICP34.5 influences herpes simplex virus type 1 maturation and egress from infected cells in vitro, J Gen Virol 1994 Dec;75 ( Pt 12):3679-86, Medline:
95088619.
Chou J, Roizman B, Herpes simplex virus 1 gamma(1)34.5 gene
function, which blocks the host response to infection, maps in the homologous domain of the genes expressed during growth arrest and DNA damage, Proc Natl Acad Sci U S A 1994 Jun 1 : Proc Natl Acad Sci U S A 1994 Jun 7;91(12):5247-51, Medline: 94261562.
McKie EA, Hope RG, Brown SM, MacLean AR, Characterization of the herpes simplex virus type 1 strain 17+ neurovirulence gene RL1 and its expression in a bacterial system, J Gen Virol 1994 Apr;75 ( Pt 4):733-41, Medline: 94201749.
Dolan A, McKie E, MacLean AR, McGeoch DJ, Status of the ICP34.5 gene in herpes simplex virus type 1 strain 17,
J Gen Virol 1992 Apr;73 ( Pt 4):971-3, Medline: 92341080.
Chou J, Kern ER, Whitley RJ, Roizman B, Mapping of herpes simplex virus-1 neurovirulence to gamma 134.5, a gene nonessential for growth in culture, Science 1990 Nov 30;250(4985):1262-6, Medline: 91057661.
Chou,J. and Roizman,B., The herpes simplex virus 1 gene for ICP34.5, which maps in inverted repeats, is conserved in several limited-passage isolates but not in strain 17syn+, J. Virol. 64 (3), 1014-1020 (1990) Medline: 90156494.
Chou J, Roizman B, The terminal a sequence of the herpes simplex virus genome contains the promoter of a gene located in the repeat sequences of the L component, Virol 1986 Feb;57(2):629-37, Medline: 86115412.
Comment:
The HSV-2 genome contains two copies of gamma34.5 one wholly within the long terminal repeat, RL region, (this location) and one in the inverted repeat region separating the long and short unique regions. There are no reported counterparts in Alphaherpesvirinae other than in HSV-1. Unlike it's HSV-1 counterpart, Harland et al. report that gamma34.5 in HSV-2 contains a 154 bp intron, Medline: 96177330.
Gamma34.5 contains four tandem nucleotide repeats, with the 19 bp repeat located wholly within the intron. In genome indices they are:
1) start 444, period 15, copy # 2.7, 96% matches w no insert/deletes.
2) start 480, period 24, copy # 2.8, 97% matches w 1 insert/delete.
3) start 943, period 19, copy # 6.7, 100% matches w no insert/deletes.
4) start 1245, period 6, copy # 7, 81% matches, 2 insert/deletes.
Gamma34.5 appears to be multi functional. Chou et.al.(1996) report that null mutants of gamma34.5 in HSV-1 are attenuated and fail to block phosphorylation of eIF-2alpha by activated protein kinase RNA-dependent kinase, allowing complete shutoff of protein synthesis and premature cell death. They suggest that one function of ICP34.5 is to block this host response to HSV infection. Chou and Roizman (1994) report that the carboxyl terminus of the HSV-1 protein is essential for this function and homologous to corresponding domains of mammalian MyD116 and GADD34. Earlier Chou et.al.(1990) reported that the HSV-1 counterpart has a profound affect on the growth of the virus in central nervous system tissue. It has a cytoplasmic location and accumulates in the infected cell late in infection.
ICP34.5 is dispensable in cell culture, Roizman, PNAS 93:11307,1996, Medline: 97030190.
Blast Summary: PSI-Blast Search
Residues 1-238 of ICP34.5 are 50% similar using gapped BLAST to residues 1-245 of both copies of ICP34.5 (HHVONE001 and HHVONE062) in Human Herpesvirus 1 (strain 17). BLAST finds no significant similarity to proteins other than ICP34.5.
Top Blast Hits: Updated monthly
Click here to view the entire PsiBlast results.
COGS Summary: COGS Search
None.
Blocks Summary: Blocks Search
None.
ProDom Summary: Protein Domain Search
Residues 20-164 constitute a neurovirulence factor domain as seen in RL1_HSV2H. Residues 165-228 are 82% similar to a neurovirulence factor domain as seen in ICP3_HSV11.
Paralogs: Local Blast Search
There are two identical copies of the gamma34.5 gene in the genome.
Pfam Summary: Pfam Search
None.
Structural Feature(s):
| Feature Type | Start | Stop |
| non-globular |
Top PDB Hits:
None.
Gene Protein Sequence:
MSRRRGPRRRGPRRRPRPGAPAVPRPGAPAVPRPGALPTADSQMVPAYDS
GTAVESAPAASSLLRRWLLVPQADDSDDADYAGNDDAEWANSPPSEGGGK
APEAPHAAPAAACPPPPPRKERGPQRPLPPHLALRLRTTTEYLARLSLRR
RRPPASPPADAPRGKVCFSPRVQVRHLVAWETAARLARRGSWARERADRD
RFRRRVAAAEAVIGPCLEPEARARARARARAHEDGGPAEEEEAAAAARGS
SAAAGPGRRAV
Gene Nucleotide Sequence: Sequence Viewer
ATGTCCCGCCGCCGGGGTCCCCGCCGCCGGGGTCCCCGGCGCCGGCCGCG
CCCCGGCGCTCCAGCCGTGCCGCGCCCCGGCGCTCCAGCCGTGCCGCGCC
CCGGCGCGCTCCCAACCGCAGACTCCCAAATGGTCCCTGCGTACGACTCG
GGAACCGCGGTCGAGAGCGCGCCGGCCGCGTCCTCGCTCCTGCGGCGCTG
GCTGCTGGTGCCCCAGGCGGACGACAGCGACGACGCGGACTACGCCGGCA
ACGACGACGCAGAGTGGGCGAACAGCCCCCCGAGCGAGGGCGGGGGGAAG
GCGCCGGAGGCCCCGCACGCCGCGCCTGCCGCCGCCTGCCCCCCGCCGCC
GCCGCGCAAGGAGCGCGGGCCGCAGCGCCCCCTTCCGCCCCACCTGGCGC
TACGGCTGCGCACCACGACGGAGTACCTGGCGCGCCTGAGCCTGCGCCGG
CGGCGGCCCCCCGCGTCCCCGCCCGCGGACGCGCCGCGCGGGAAGGTACG
CCTCCCCTCCGACCCCCTGACGCCCCTCCGACCCCCTGACGCCCCTCCGA
CCCCCTGACGCCCCTCCGACCCCCTGACGCCCCTCCGACCCCCTGACGCC
CCTCCGACCCCCTGACGCCCCTCCGACCCCCGTGTCTCCCCGCCCGCAGG
TGTGCTTCTCGCCGCGCGTGCAGGTGCGCCATCTGGTGGCCTGGGAGACG
GCCGCGCGCCTGGCCCGACGGGGGTCCTGGGCGCGCGAGCGGGCCGACCG
CGACCGGTTCCGGCGCCGCGTGGCGGCGGCCGAGGCGGTCATCGGACCGT
GCCTGGAGCCCGAGGCCCGAGCTCGGGCCCGAGCCCGAGCCCGGGCCCAC
GAAGACGGCGGACCCGCGGAGGAGGAGGAGGCGGCGGCGGCGGCGCGCGG
GTCCTCCGCCGCCGCGGGCCCGGGCCGTCGGGCGGTCTAG