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

1988 ◽  
Vol 2 (6) ◽  
pp. 718-729 ◽  
Author(s):  
S J Triezenberg ◽  
R C Kingsbury ◽  
S L McKnight
Keyword(s):  
Gene Expression ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Immediate Early Gene ◽  
Early Gene ◽  
Immediate Early ◽  
Early Gene Expression ◽  
Simplex Virus

scholarly journals Herpes Simplex Virus Downregulates Secretory Leukocyte Protease Inhibitor: a Novel Immune Evasion Mechanism

2008 ◽  
Vol 82 (19) ◽  
pp. 9337-9344 ◽  
Author(s):  
Esra Fakioglu ◽  
Sarah S. Wilson ◽  
Pedro M. M. Mesquita ◽  
Ehsan Hazrati ◽  
Natalia Cheshenko ◽  
...  
Keyword(s):  
Gene Expression ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Protease Inhibitor ◽  
Immediate Early Gene ◽  
Secretory Leukocyte Protease Inhibitor ◽  
Early Gene ◽  
Immediate Early ◽  
Early Gene Expression ◽  
Simplex Virus

ABSTRACT Secretory leukocyte protease inhibitor (SLPI), an anti-inflammatory mediator of mucosal immunity, inhibits human immunodeficiency virus (HIV) and herpes simplex virus (HSV) in cell culture. Epidemiological studies demonstrate that higher concentrations of SLPI in mucosal secretions are associated with a reduced risk of HIV transmission. The current studies were designed to test the hypothesis that HSV triggers a loss of SLPI to evade innate immunity and that this response may contribute to the increased risk of HIV infection in the setting of HSV infection. Exposure of human cervical epithelial cells to HSV-1 or HSV-2, but not HIV or vesicular stomatitis virus, triggered a significant and sustained reduction in SLPI levels. The reduction persisted when cells were infected in the presence of acyclovir but not following infection with UV-inactivated virus, indicating that viral gene expression, but not replication, is required. Reverse transcriptase PCR studies demonstrated that the loss of SLPI is mediated by downregulation of gene expression. SLPI downregulation was associated with activation of NF-κB signaling pathways and upregulation of proinflammatory cytokines, consistent with the known inhibitor effects of SLPI on NF-κB pathways. The downregulation mapped to viral early-gene expression, as variants impaired in expression of the ICP4 or ICP0 immediate-early gene failed to downregulate SLPI or activate NF-κB. Together, these results identify a novel role for HSV immediate-early-gene expression in regulating mucosal immune responses.

Regulation of Herpes Simplex virus immediate early gene expression

1998 ◽  
Vol 26 (3) ◽  
pp. S258-S258 ◽  
Author(s):  
Helen L. Jameson ◽  
Caroline H. Arnott ◽  
Karen A. Lillycrop
Keyword(s):  
Gene Expression ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Immediate Early Gene ◽  
Early Gene ◽  
Immediate Early ◽  
Early Gene Expression ◽  
Simplex Virus

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

1985 ◽  
Vol 5 (8) ◽  
pp. 1997-2008 ◽  
Author(s):  
N A DeLuca ◽  
P A Schaffer
Keyword(s):  
Gene Expression ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Immediate Early Genes ◽  
Early Gene ◽  
Immediate Early ◽  
Temperature Sensitive ◽  
Wild Type ◽  
Early Genes ◽  
Simplex Virus

To better define the activities on herpes simplex virus type 1 gene expression of temperature-sensitive and wild-type forms of the transcriptional regulatory protein ICP4, regulatory sequences from immediate-early, early, and late herpes simplex virus genes were fused to the gene for chloramphenicol acetyltransferase (CAT). These constructs were used in trans induction and cotransfection experiments with wild-type and temperature-sensitive mutant alleles of ICP4. The ICP4 genes used in this study were cloned from the KOS strain (wild type) and two phenotypically distinct temperature-sensitive ICP4 mutants, tsB32 and tsL14 (DeLuca et al., J. Virol. 52:767-776, 1984), both alone and in conjunction with three other immediate-early genes. The latter series of plasmids was used to assess the influence of additional immediate-early gene products on gene expression in the presence of a given ICP4 allele. The results of this study demonstrate that the phenotypes of these ICP4 mutants observed in cell culture at the nonpermissive temperature were determined in part by activities associated with the mutant ICP4 polypeptides and that these activities differed from those of wild-type ICP4. Low levels of wild-type ICP4 had a marginal but reproducible stimulatory effect on immediate-early CAT gene expression, especially the pIE4/5CAT chimera. This effect was diminished with increasing quantities of ICP4, suggesting an inhibitory role for the wild-type form of the protein. The ICP4 mutants had a strong stimulatory effect on immediate-early CAT expression, consistent with their phenotypes at 39 degrees C. The mutant forms of the ICP4 polypeptide differed in their ability to induce CAT activity from an early chimeric gene. Thus, the tsL14 form of ICP4 was effective in early gene induction (i.e., ptkCAT was induced), whereas the ICP4 derived from tsB32 was slightly inhibitory. 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. Cotransfecting tsL14 ICP4 with the other immediate-early genes resulted in activation of p5CAT but not pL42CAT. 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.

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