Disease relevance of HHV5wtgp107

• Taken together, these data demonstrate specific activation of c-FLIP by HCMV IE2 and indicate a novel role for c-FLIP in the pathogenesis of HCMV retinitis [1].
• The 86-kDa IE2 protein (IE2-p86) of human cytomegalovirus (HCMV) is a potent transactivator of viral as well as cellular promoters [2].
• Consequently, the sequence requirements of the HIV-1 LTR for transactivation by HCMV can be reproduced by these IE1 and IE2 gene products of HCMV [3].
• A 10-base-pair element of the human immunodeficiency virus type 1 long terminal repeat (LTR) is an absolute requirement for transactivation by the human cytomegalovirus 72-kilodalton IE1 protein but can be compensated for by other LTR regions in transactivation by the 80-kilodalton IE2 protein [3].
• Deletion mutants of HHV-6 variant A IE2 allowed us to map functional transactivation domains acting on complex and minimal promoter sequences [4].

High impact information on HHV5wtgp107

• Therefore, we propose a protein-tethered transactivation mechanism in which the il1b promoter-bound Spi-1 wHTH tethers IE2, which provides a TAD, resulting in the transactivation of il1b [5].
• Previously, we showed that viral immediate early 2 (IE2) protein may allow HCMV to evade the immune control by killing the Fas receptor-positive T lymphocytes attracted to the infected retina with increased secretion of Fas ligand (FasL) [1].
• Moreover, c-FLIP up-regulation by IE2 appeared to involve PI3K and might also render cells resistant to TRAIL-mediated death [1].
• However, a strong reduction of IE2-mediated transactivation of two viral early promoters and a heterologous promoter was observed in cotransfection analysis with the SUMOylation-defective mutant [2].
• Furthermore, fibroblasts infected with CR208 at a low multiplicity failed to form viral DNA replication compartments, despite having expressed IE2 p86 [6].

Chemical compound and disease context of HHV5wtgp107

• The human cytomegalovirus early promoter for the UL4 gene, which codes for an early viral envelope glycoprotein designated gpUL4, requires immediate-early viral protein two (IE2) synthesis to be activated (C.-P. Chang, C. L. Malone, and M. F. Stinski, J. Virol. 63:281, 1989) [7].

Biological context of HHV5wtgp107

• In transient transfection assays, the viral IE2 protein negated the effect of an upstream cis-acting negative element and enhanced downstream gene expression [7].
• One of these isoforms, the IE86 protein (UL122, IE2), is a DNA-binding protein that represses the MIEP through its cognate recognition sequence (designated the cis repression signal [crs]) located between the TATA box and the initiation site of transcription [8].
• Immunofluorescence analyses revealed that 1-2 h after infection (p.i.) with HCMV the immediate early gene (IE) products IE1 and IE2 transiently colocalize with ND10 proteins [9].
• The first three exons (the first is noncoding) are spliced to exon 4 to form IE1 and to exon 5 to form IE2 [10].
• We investigated the binding of cellular or viral IE2 protein to the negative regulatory region [11].

Anatomical context of HHV5wtgp107

• When the selected ribozymes were expressed in cultured cells, they were more effective in inhibiting viral IE1/IE2 and TK expression and viral growth than the wildtype ribozyme sequence [12].
• In order to study the expression and function of these IE gene products, we established several HeLa cell lines that stably expressed the 68-kD IE1 protein, the 82-kD IE2 protein, or both proteins [13].
• Furthermore, expression of both the IE1 and IE2 proteins was increased by treatment of these cell lines with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate [13].

References