herpes simplex virus protein vmw65


Summary: Trans-acting protein that combines with host factors to induce immediate early gene transcription in herpes simplex virus.

Top Publications

  1. Wilson A, LaMarco K, Peterson M, Herr W. The VP16 accessory protein HCF is a family of polypeptides processed from a large precursor protein. Cell. 1993;74:115-25 pubmed
    ..When expressed in human cells, this large open reading frame encodes both the 300 kd and smaller HCF polypeptides, indicating that the smaller polypeptides arise by processing of the 300 kd protein. ..
  2. Preston C, McFarlane M. Cytodifferentiating agents affect the replication of herpes simplex virus type 1 in the absence of functional VP16. Virology. 1998;249:418-26 pubmed
  3. Stagljar I, Korostensky C, Johnsson N, te Heesen S. A genetic system based on split-ubiquitin for the analysis of interactions between membrane proteins in vivo. Proc Natl Acad Sci U S A. 1998;95:5187-92 pubmed
    ..Specific interactions are detected between Wbp1p and Ost1p, but not between Wbp1p and Alg5p. The new system might be useful as a genetic and biochemical tool for the analysis of interactions between membrane proteins in vivo. ..
  4. Kim J, Mandarino A, Chao M, Mohr I, Wilson A. Transient reversal of episome silencing precedes VP16-dependent transcription during reactivation of latent HSV-1 in neurons. PLoS Pathog. 2012;8:e1002540 pubmed publisher
    ..Thus regulated localization of de novo synthesized VP16 is likely to be a critical determinant of HSV-1 reactivation in sympathetic neurons. ..
  5. Herrera F, Triezenberg S. VP16-dependent association of chromatin-modifying coactivators and underrepresentation of histones at immediate-early gene promoters during herpes simplex virus infection. J Virol. 2004;78:9689-96 pubmed
    ..Thus, the VP16 activation domain is responsible for recruiting general transcription factors and coactivators to IE promoters and also for dramatically reducing the association of histones with those promoters. ..
  6. Mahajan S, Wilson A. Mutations in host cell factor 1 separate its role in cell proliferation from recruitment of VP16 and LZIP. Mol Cell Biol. 2000;20:919-28 pubmed
  7. Jonker H, Wechselberger R, Boelens R, Folkers G, Kaptein R. Structural properties of the promiscuous VP16 activation domain. Biochemistry. 2005;44:827-39 pubmed
    ..The models showed multiple distinct binding surfaces upon interaction with various partners, providing an explanation for the promiscuous properties, cooperativity, and the high activity of this activation domain. ..
  8. Tumbar T, Belmont A. Interphase movements of a DNA chromosome region modulated by VP16 transcriptional activator. Nat Cell Biol. 2001;3:134-9 pubmed
    ..In contrast, VP16 AAD targeting induced this site's permanent interior localization in early G1. A single transcriptional activator therefore can modify the cell-cycle-dependent programme of intranuclear positioning of chromosome loci. ..
  9. Naldinho Souto R, Browne H, Minson T. Herpes simplex virus tegument protein VP16 is a component of primary enveloped virions. J Virol. 2006;80:2582-4 pubmed

More Information


  1. Barreca C, O Hare P. Characterization of a potent refractory state and persistence of herpes simplex virus 1 in cell culture. J Virol. 2006;80:9171-80 pubmed
    ..These results may be relevant to consider in studies of HSV latency in different animal models. ..
  2. Langlois C, Mas C, Di Lello P, Jenkins L, Legault P, Omichinski J. NMR structure of the complex between the Tfb1 subunit of TFIIH and the activation domain of VP16: structural similarities between VP16 and p53. J Am Chem Soc. 2008;130:10596-604 pubmed publisher
  3. Mittler G, Stühler T, Santolin L, Uhlmann T, Kremmer E, Lottspeich F, et al. A novel docking site on Mediator is critical for activation by VP16 in mammalian cells. EMBO J. 2003;22:6494-504 pubmed
    ..Despite many known targets of VP16, ARC92/ACID1 appears to impose a critical control on transcription activation by VP16 in mammalian cells. ..
  4. Wysocka J, Herr W. The herpes simplex virus VP16-induced complex: the makings of a regulatory switch. Trends Biochem Sci. 2003;28:294-304 pubmed
    ..The activities of Oct-1 and HCF-1 - two important regulators of cellular gene expression and proliferation - illuminate strategies by which HSV might coexist with its host. ..
  5. Thompson R, Preston C, Sawtell N. De novo synthesis of VP16 coordinates the exit from HSV latency in vivo. PLoS Pathog. 2009;5:e1000352 pubmed publisher
    ..HSV reactivation from latency conforms to a model in which stochastic derepression of the VP16 promoter and expression of VP16 initiates entry into the lytic cycle. ..
  6. Hirai H, Tani T, Kikyo N. Structure and functions of powerful transactivators: VP16, MyoD and FoxA. Int J Dev Biol. 2010;54:1589-96 pubmed publisher
  7. Wysocka J, Myers M, Laherty C, Eisenman R, Herr W. Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1. Genes Dev. 2003;17:896-911 pubmed
    ..These results suggest that HCF-1 can broadly regulate transcription, both positively and negatively, through selective modulation of chromatin structure. ..
  8. Schratt G, Philippar U, Berger J, Schwarz H, Heidenreich O, Nordheim A. Serum response factor is crucial for actin cytoskeletal organization and focal adhesion assembly in embryonic stem cells. J Cell Biol. 2002;156:737-50 pubmed
    ..Our findings suggest an involvement of SRF in cell migratory processes in multicellular organisms. ..
  9. Kurosu T, Peterlin B. VP16 and ubiquitin; binding of P-TEFb via its activation domain and ubiquitin facilitates elongation of transcription of target genes. Curr Biol. 2004;14:1112-6 pubmed
    ..Thus, the ubiquitylation of AADs increases their interaction with P-TEFb and augments rates of elongation of transcription. ..
  10. Hall D, Struhl K. The VP16 activation domain interacts with multiple transcriptional components as determined by protein-protein cross-linking in vivo. J Biol Chem. 2002;277:46043-50 pubmed
    ..We show that the VP16 activation domain directly interacts with TATA-binding protein (TBP), TFIIB, and the SAGA histone acetylase complex in vivo. ..
  11. Bearer E, Breakefield X, Schuback D, Reese T, LaVail J. Retrograde axonal transport of herpes simplex virus: evidence for a single mechanism and a role for tegument. Proc Natl Acad Sci U S A. 2000;97:8146-50 pubmed
  12. Kristie T, Vogel J, Sears A. Nuclear localization of the C1 factor (host cell factor) in sensory neurons correlates with reactivation of herpes simplex virus from latency. Proc Natl Acad Sci U S A. 1999;96:1229-33 pubmed
    ..The regulated localization suggests that C1 is a critical switch determinant of the viral lytic-latent cycle. ..
  13. Miller C, Danaher R, Jacob R. ICP0 is not required for efficient stress-induced reactivation of herpes simplex virus type 1 from cultured quiescently infected neuronal cells. J Virol. 2006;80:3360-8 pubmed
  14. Liu M, Tang J, Wang X, Yang T, Geller A. Enhanced long-term expression from helper virus-free HSV-1 vectors packaged in the presence of deletions in genes that modulate the function of VP16, U L 46 and U L 47. J Neurosci Methods. 2005;145:1-9 pubmed
    ..The implications of these results for strategies to improve long-term expression are discussed...
  15. Barreca C, O Hare P. Suppression of herpes simplex virus 1 in MDBK cells via the interferon pathway. J Virol. 2004;78:8641-53 pubmed
    ..We believe the conclusions have significant implications for the study of HSV-1 and interferon signaling both in culture and in animal models. ..
  16. Kutluay S, DeVos S, Klomp J, Triezenberg S. Transcriptional coactivators are not required for herpes simplex virus type 1 immediate-early gene expression in vitro. J Virol. 2009;83:3436-49 pubmed publisher
  17. Kutluay S, Triezenberg S. Regulation of histone deposition on the herpes simplex virus type 1 genome during lytic infection. J Virol. 2009;83:5835-45 pubmed publisher
  18. Proença J, Coleman H, Nicoll M, Connor V, Preston C, Arthur J, et al. An investigation of herpes simplex virus promoter activity compatible with latency establishment reveals VP16-independent activation of immediate-early promoters in sensory neurones. J Gen Virol. 2011;92:2575-85 pubmed publisher
    ..We conclude that only IE promoter activation can efficiently precede latency establishment and that this activation is likely to occur through a VP16-independent mechanism. ..
  19. Herr W, Cleary M. The POU domain: versatility in transcriptional regulation by a flexible two-in-one DNA-binding domain. Genes Dev. 1995;9:1679-93 pubmed
  20. Suzuki N, Peter W, Ciesiolka T, Gruss P, Scholer H. Mouse Oct-1 contains a composite homeodomain of human Oct-1 and Oct-2. Nucleic Acids Res. 1993;21:245-52 pubmed
    ..Nevertheless, VP16 interacts albeit weakly with murine Oct-1. We speculate that the differences in the human and mouse Oct-1 homeodomains reflect host-specific differences in protein-protein interactions. ..
  21. Hancock M, Cliffe A, Knipe D, Smiley J. Herpes simplex virus VP16, but not ICP0, is required to reduce histone occupancy and enhance histone acetylation on viral genomes in U2OS osteosarcoma cells. J Virol. 2010;84:1366-75 pubmed publisher
    ..We also show that HSV infection results in decreased histone levels on some actively transcribed genes within the cellular genome, demonstrating that viral infection alters cellular chromatin structure...
  22. Cun W, Guo L, Zhang Y, Liu L, Wang L, Li J, et al. Transcriptional regulation of the Herpes Simplex Virus 1alpha-gene by the viral immediate-early protein ICP22 in association with VP16. Sci China C Life Sci. 2009;52:344-51 pubmed publisher
    ..These findings support the possibility that ICP22 and VP16 control transcription of HSV1alpha genes in a common pathway for the establishment of either viral lytic or latent infections. ..
  23. Ikeda K, Stuehler T, Meisterernst M. The H1 and H2 regions of the activation domain of herpes simplex virion protein 16 stimulate transcription through distinct molecular mechanisms. Genes Cells. 2002;7:49-58 pubmed
    ..The H1 and H2 regions of the VP16 activation domain activate transcription via distinct pathways. The H2 requires CBP for activation, whereas the H1 may function through Mediator and general transcription factors. ..
  24. Yamauchi Y, Kiriyama K, Kubota N, Kimura H, Usukura J, Nishiyama Y. The UL14 tegument protein of herpes simplex virus type 1 is required for efficient nuclear transport of the alpha transinducing factor VP16 and viral capsids. J Virol. 2008;82:1094-106 pubmed
    ..The tegument protein UL14 could be part of the machinery that regulates HSV-1 replication. ..
  25. Wilson A, Freiman R, Goto H, Nishimoto T, Herr W. VP16 targets an amino-terminal domain of HCF involved in cell cycle progression. Mol Cell Biol. 1997;17:6139-46 pubmed
    ..Rescue of the tsBN67 cell proliferation defect by HCF, however, requires both the VP16 interaction domain and an adjacent basic region, indicating that HCF utilizes multiple regions to promote cell cycle progression. ..
  26. Kobayashi N, Horn P, Sullivan S, Triezenberg S, Boyer T, Berk A. DA-complex assembly activity required for VP16C transcriptional activation. Mol Cell Biol. 1998;18:4023-31 pubmed
    ..These results argue that the ability of VP16C to increase the rate and extent of DA-complex assembly makes a significant contribution to the overall mechanism of transcriptional activation in vivo. ..
  27. Näär A, Beaurang P, Zhou S, Abraham S, Solomon W, Tjian R. Composite co-activator ARC mediates chromatin-directed transcriptional activation. Nature. 1999;398:828-32 pubmed
    ..Thus, ARC/DRIP is a large composite co-activator that belongs to a family of related cofactors and is targeted by different classes of activator to mediate transcriptional stimulation. ..
  28. Smiley J, Duncan J. Truncation of the C-terminal acidic transcriptional activation domain of herpes simplex virus VP16 produces a phenotype similar to that of the in1814 linker insertion mutation. J Virol. 1997;71:6191-3 pubmed
    ..Taken in combination, these data confirm the key role of VP16 in triggering the onset of the HSV lytic cycle. ..
  29. Lu R, Yang P, O Hare P, Misra V. Luman, a new member of the CREB/ATF family, binds to herpes simplex virus VP16-associated host cellular factor. Mol Cell Biol. 1997;17:5117-26 pubmed
    ..Luman appears to be a ubiquitous transcription factor, and its mRNA was detected in all human adult and fetal tissues examined. The possible role of HCF in regulating the function of this ubiquitous transcription factor is discussed. ..
  30. La Boissière S, Izeta A, Malcomber S, O Hare P. Compartmentalization of VP16 in cells infected with recombinant herpes simplex virus expressing VP16-green fluorescent protein fusion proteins. J Virol. 2004;78:8002-14 pubmed
    ..Vesicular clusters containing VP16 were transported within projections to the termini, which developed bulbous ends and appeared to embed into the membranes of adjacent uninfected cells. ..
  31. Yang T, Zhang G, Zhang W, Sun M, Wang X, Geller A. Enhanced reporter gene expression in the rat brain from helper virus-free HSV-1 vectors packaged in the presence of specific mutated HSV-1 proteins that affect the virion. Brain Res Mol Brain Res. 2001;90:1-16 pubmed
    ..Vectors packaged in the presence of mutated vhs or U(S)11 displayed minimal changes in expression. ..
  32. Lu R, Misra V. Potential role for luman, the cellular homologue of herpes simplex virus VP16 (alpha gene trans-inducing factor), in herpesvirus latency. J Virol. 2000;74:934-43 pubmed
    ..Interestingly, Luman could activate the promoters of IE110 and LAT, two genes that are critical for reactivation of HSV-1 from latency. This suggests a role for Luman in the reactivation process as well. ..
  33. McFadden D, McAnally J, Richardson J, Charité J, Olson E. Misexpression of dHAND induces ectopic digits in the developing limb bud in the absence of direct DNA binding. Development. 2002;129:3077-88 pubmed
    ..These findings suggest that dHAND may act via novel transcriptional mechanisms mediated by protein-protein interactions independent of direct DNA binding. ..
  34. Hafezi W, Lorentzen E, Eing B, Müller M, King N, Klupp B, et al. Entry of herpes simplex virus type 1 (HSV-1) into the distal axons of trigeminal neurons favors the onset of nonproductive, silent infection. PLoS Pathog. 2012;8:e1002679 pubmed publisher
    ..HSV-1 entry into distal axons results in an insufficient transactivation of IE gene expression and favors the establishment of a nonproductive, silent infection in trigeminal neurons. ..
  35. Cao L, Tang D, Horb M, Li S, Yang L. High glucose is necessary for complete maturation of Pdx1-VP16-expressing hepatic cells into functional insulin-producing cells. Diabetes. 2004;53:3168-78 pubmed
    ..Thus, transdifferentiation of hepatocytes into functional IPCs may serve as a viable therapeutic option for patients with type 1 diabetes. ..
  36. Parcy F, Bomblies K, Weigel D. Interaction of LEAFY, AGAMOUS and TERMINAL FLOWER1 in maintaining floral meristem identity in Arabidopsis. Development. 2002;129:2519-27 pubmed
    ..These observations contrast with previous findings that LEAFY acts as a direct activator of floral homeotic genes, supporting the hypothesis that the transcriptional activity of LEAFY is dependent on specific co-regulators. ..
  37. Preston C, Rinaldi A, Nicholl M. Herpes simplex virus type 1 immediate early gene expression is stimulated by inhibition of protein synthesis. J Gen Virol. 1998;79 ( Pt 1):117-24 pubmed
    ..The results also highlight previously unrecognized difficulties in analysing the intrinsic activities of promoters when cloned into the HSV-1 genome. ..
  38. Wang L, Turcotte B, Guarente L, Berger S. The acidic transcriptional activation domains of herpes virus VP16 and yeast HAP4 have different co-factor requirements. Gene. 1995;158:163-70 pubmed
    ..These results strongly suggest that HAP4 and VP16 have distinct cofactor requirements, although they are both acidic activators. ..
  39. Klein T, Seugnet L, Haenlin M, Martinez Arias A. Two different activities of Suppressor of Hairless during wing development in Drosophila. Development. 2000;127:3553-66 pubmed
    ..After its release Su(H) can activate gene expression in absence of Nintra. ..
  40. Warren L, Ni Y, WANG J, Guo X. Feeder-free derivation of human induced pluripotent stem cells with messenger RNA. Sci Rep. 2012;2:657 pubmed publisher
  41. Lei J, Miao J, Li X, Schonig K, Bujard H, Xue C. [Preliminary study on regulable DNA vaccines against Plasmodium falciparum]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2004;20:356-9 pubmed
    ..In contrast, the mice immunized by pTL-8/AMA-1(rtTA) and pUHS6-1 with dox produced high level of antibodies. pTL-8/AMA-1(rtTA) combined with pUHS6-1 is a good regulable DNA vaccine candidate against Plasmodium falciparum. ..
  42. Bordonaro M, Lazarova D, Sartorelli A. Pharmacological and genetic modulation of Wnt-targeted Cre-Lox-mediated gene expression in colorectal cancer cells. Nucleic Acids Res. 2004;32:2660-74 pubmed
    ..These findings demonstrated that the Cre-Lox system, in combination with pharmacological and genetic modulators, represents effective methodology for enhancing Wnt-targeted gene therapy. ..
  43. Gillette K, Misra V, Bratanich A. Sequence analysis of the alpha trans-inducing factor of bovine herpesvirus type 5 (BHV-5). Virus Genes. 2002;24:149-52 pubmed
    ..Amino acid alignment of the alpha-tifs of BHV-1 and BHV-5 with other alphaherpesviruses indicates areas of conserved motifs but also important differences located mainly at the amino and carboxyl termini...
  44. Stege J, Guan X, Ho T, Beachy R, Barbas C. Controlling gene expression in plants using synthetic zinc finger transcription factors. Plant J. 2002;32:1077-86 pubmed
    ..These results provide evidence that synthetic zinc finger proteins can be used to manipulate the expression of endogenous genes in plants. ..
  45. Liu M, Wang X, Geller A. Improved long-term expression from helper virus-free HSV-1 vectors packaged using combinations of mutated HSV-1 proteins that include the UL13 protein kinase and specific components of the VP16 transcriptional complex. BMC Mol Biol. 2009;10:58 pubmed publisher
    ..Implications of these results for strategies to further improve long-term expression are discussed. Moreover, long-term expression will benefit specific gene therapy applications. ..
  46. Johnson D, Cress W, Jakoi L, Nevins J. Oncogenic capacity of the E2F1 gene. Proc Natl Acad Sci U S A. 1994;91:12823-7 pubmed
    ..Cells transfected with E2F1 and DP1 or the E2F1-VP16 chimera form colonies in soft agar and induce tumor formation in nude mice. We conclude that deregulated E2F1 expression and function can have oncogenic consequences. ..
  47. Ma Q, Dong L, Whitlock J. Transcriptional activation by the mouse Ah receptor. Interplay between multiple stimulatory and inhibitory functions. J Biol Chem. 1995;270:12697-703 pubmed
    ..The inhibitory activity depends upon the cell type in which AhR is expressed, implying that a cell-specific protein mediates the effect. ..
  48. Li J, Blue R, Zeitler B, Strange T, Pearl J, Huizinga D, et al. Activation domains for controlling plant gene expression using designed transcription factors. Plant Biotechnol J. 2013;11:671-80 pubmed publisher
    ..These results demonstrate that plant sequences capable of facilitating transcriptional activation can be found and, when fused to DNA-binding proteins, can enhance gene expression. ..
  49. Esengil H, Chang V, Mich J, Chen J. Small-molecule regulation of zebrafish gene expression. Nat Chem Biol. 2007;3:154-5 pubmed
    ..Coupled with tissue-specific promoters, this system provides multidimensional control of gene expression and will enable new models of human disorders and diseases. ..
  50. Yang L. Liver stem cell-derived beta-cell surrogates for treatment of type 1 diabetes. Autoimmun Rev. 2006;5:409-13 pubmed
  51. Preston C, Nicholl M. Human cytomegalovirus tegument protein pp71 directs long-term gene expression from quiescent herpes simplex virus genomes. J Virol. 2005;79:525-35 pubmed
    ..The ability to provoke slow reactivation of quiescent genomes, in conjunction with cell survival, represents a novel property for a viral structural protein. ..
  52. Dibner C, Elias S, Frank D. XMeis3 protein activity is required for proper hindbrain patterning in Xenopus laevis embryos. Development. 2001;128:3415-26 pubmed
    ..These results provide evidence that XMeis3 protein in the hindbrain is required to modify anterior neural-inducing activity, thus, enabling the transformation of these cells to posterior fates. ..
  53. Papageorgiou K, Isenberg D, Latchman D. Optimisation of herpes simplex virus-based vectors for delivery to human peripheral blood mononuclear cells. J Immunol Methods. 2002;270:235-46 pubmed
    ..This optimised HSV vector may thus represent an effective tool for gene delivery to unstimulated PBMCs in culture. ..