Activation of immediate-early, early, and late promoters by temperature-sensitive and wild-type forms of herpes simplex virus type 1 protein ICP4.

Activation of immediate-early, early, and late promoters by temperature-sensitive and wild-type forms of herpes simplex virus type 1 protein ICP4.

Herpes simplex virus (HSV) enters cells by fusion at plasma membranes or endosomes. Truncated forms of gD lacking the transmembrane and cytoplasmic tail regions have been shown to bind to cells and block plaque formation. In accordance with the guiding principles established by George Ellery Hale in 1914, PNAS publishes brief first announcements of Academy Members’ and Foreign Associates’ more important contributions to research and of work that appears to a Member to be of particular importance. The second glycoprotein, having a molecular weight of approximately 230,000, was identified as a multimeric form of the gC glycoprotein. The crystal structure of HSV-2 gH/gL was obtained with a functional protein that had a deletion of 28 residues at the gH N terminus (gHΔ48/gL). Furthermore, the mouse genital model showed quantitative differences in the degree of protection induced by various viral vaccine constructs. The data suggest that virions contain two populations of Vhs that are packaged by different pathways.
Activation of immediate-early, early, and late promoters by temperature-sensitive and wild-type forms of herpes simplex virus type 1 protein ICP4.

Ryan, J. After initial replication in epithelial cells, herpes simplex viruses (HSVs) establish latent infections in neurons innervating these regions. The ICP4 mutants had a strong stimulatory effect on immediate-early CAT expression, consistent with their phenotypes at 39 degrees C. Taken together, the data suggest that ICP4 interacts with components of TFIID and Mediator in the context of viral infection, and this may explain the broad transactivation properties of ICP4. On de novo infection, VP16 is released into the cell and associates with two cellular factors, HCF (also called C1, CFF, and VCAF) and Oct-1, on HSV IE promoters at VP16-responsive sites called TAATGARAT. Cotransfection of tsB32 ICP4 simultaneously with other immediate-early genes resulted in a marginal increase in ptkCAT induction. This induction was enhanced when the gene for ICP4 was inactivated by restriction enzyme cleavage, substantiating the inhibitory effect of the tsB32 form of ICP4.

The two mutant ICP4 genes (tsB32 and tsL14) were unable to trans-activate either of the late CAT constructs (p5CAT and pL42CAT) tested. © 1995. Taken together, these studies demonstrate that (i) low levels of wild-type ICP4 have stimulatory effect on immediate-early promoters and that higher concentrations of wild-type ICP4 have an inhibitory effect on these promoters, (ii) isolated mutant form of ICP4 exhibit activities that reflect the phenotypes of the mutants from which they were isolated, and (iii) immediate-early gene products other than ICP4 are involved in determining the distinct phenotypes of the two mutants at 39 degrees Celsius. Entry into CHO cells is through acidic endosomes, irrespective of the presence of αVβ3-integrin. Get a printable copy (PDF file) of the complete article (2.8M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

You may also like