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June 1, 1988Genes & DevelopmentOpen Access

Functional dissection of VP16, the trans-activator of herpes simplex virus immediate early gene expression.

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Population

Cells cotransfected with a plasmid encoding VP16 and a reporter gene driven by immediate early…

Design

Preclinical

Authors

STSteven J. TriezenbergVan Andel InstituteRKRobert C. KingsburyCarnegie Institution for ScienceSMSteven L. McKnightUniversity of Geneva

Discussion

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Overview

These VP16 domains may aid HSV antiviral design; leaves open translation from animal models to human efficacy.

Key Points

  • To characterize the structural domains of herpes simplex virus type 1 VP16 polypeptide responsible for trans-activating immediate early viral gene expression.
  • Generated mutant variants across the 65-kD VP16 polypeptide sequence.
  • Cotransfected cultured cells with VP16-expressing plasmids and reporter genes controlled by viral immediate early cis-regulatory elements to evaluate transcriptional activity.
  • Identified an essential activation domain located within the acidic carboxy-terminal 78 amino acids of VP16.
  • Determined that an amino-terminal domain confers immediate early gene specificity, mediated through protein-protein rather than direct protein-DNA interactions.

Structured PICO

P
Population
Cells cotransfected with a plasmid encoding VP16 and a reporter gene driven by immediate early (IE) cis-regulatory sequences
I
Intervention
Mutant forms of VP16
O
Outcome
Trans-activating function (induction of IE gene expression)surrogate

VP16 achieves immediate early gene specificity through protein-protein interactions mediated by specific amino-terminal and carboxy-terminal domains.

Cite This Study

Triezenberg et al. (1988) studied this question.

synapsesocial.com/papers/6a1bf4ebbc71fb1015a91cdehttps://doi.org/10.1101/gad.2.6.718
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Also Consider

Synapse has enriched 4 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Structural features of the herpes simplex virus alpha gene 4, 0, and 27 promoter-regulatory sequences which confer alpha regulation on chimeric thymidine kinase genes1982 · 297 citations
  2. 2The immediate-early enhancer element of herpes simplex virus type 1 can replace a regulatory region of the c-Ha-ras1 oncogene required for transformation1985 · 19 citations
  3. 3Effects of deletions on expression of the herpes simplex virus thymidine kinase gene from the intact viral genome: the amino terminus of the enzyme is dispensable for catalytic activity1984 · 63 citations
  4. 4Functional analysis of a herpes simplex virus type 1 promoter: identification of far-upstream regulatory sequences1983 · 98 citations