Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001486 (Adenovirus)
 3,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have reported previously that human group C adenoviruses down-regulate the epidermal growth factor (EGF) receptor (EGF-R) (C. R. Carlin, A. E. Tollefson, H. A. Brady, B. L. Hoffman, and W. S. M. Wold, Cell 57:135-144, 1989). Expression of a 13.7-kDa protein encoded by a gene in the E3 transcription unit is necessary and sufficient for this effect (Carlin et al., Cell, 1989; B. L. Hoffman, A. Ullrich, W. S. M. Wold, and C. R. Carlin, Mol. Cell. Biol. 10:5521-5524, 1990). We show here that EGF-R down-regulation is accelerated in cells which overexpress the receptor when these cells are infected with virus mutants that overproduce the 13.7-kDa protein compared with wild-type virus. This is in contrast to EGF stimulation, for which others have shown that high concentrations of ligand are associated with low rates of receptor internalization in EGF-R-overexpressing cells (D. Kuppuswamy and L. J. Pike, J. Biol. Chem. 264:3357-3363, 1989; H. S. Wiley, J. Cell Biol. 107:801-810, 1988). We also show that the E3 protein is not present in media conditioned by infected cells and that it does not induce secretion of an EGF-like autocrine factor. Moreover, while mature membrane-bound EGF-R is down-regulated, the precursor of the membrane-bound form is not. Adenovirus infection also does not affect receptor-related molecules expressed in the secretory pathway. Interestingly, adenovirus-induced down-regulation is not regulated by concentrations of EGF associated with a slow rate of internalization in A431 cells. This suggests that 13.7-kDa protein expression triggers receptor entry by a novel ligand-independent pathway or, alternatively, that it compensates for a cellular factor that may be rate limiting during EGF-mediated endocytosis.
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PMID:Evidence for intracellular down-regulation of the epidermal growth factor (EGF) receptor during adenovirus infection by an EGF-independent mechanism. 172 83

Human adenoviruses are providing insights into strategies that viruses may adopt to evade immune surveillance. There are 47 serotypes that form six groups (A to F) with different genetic and biological properties. Adenovirus type 2 (Ad2) and Ad5, two group C types, the most common and best understood in terms of molecular biology, cause respiratory infections in young children and often form persistent infections. Following infection, the linear duplex DNA genome is expressed in two broad phases: "early", when viral proteins function to usurp the cell; and "late", when viral DNA and structural proteins are synthesized and virions are assembled. One of the early transcription units, region E3, encodes two proteins that appear to counteract different branches of the host's anti-viral defenses. A 19,000 Mr protein called gp19K protects cells against cytolysis by adenovirus-specific cytotoxic T lymphocytes (CTL). Gp19K has two properties that are crucial to this function: it is localized in the endoplasmic reticulum, and it binds strongly to class I antigens of the major histocompatibility complex (MHC). The effect of these two properties is to block transport of class I antigens to the cell surface. In order to lyse adenovirus-infected cells, CTL must recognize adenovirus peptide antigens complexed with class I major histocompatability complex antigens displayed on the cell surface. Since gp19K prevents this, it renders the cell effectively invisible to CTL. The second anti-immune E3 protein is a 14,700 Mr protein called 14.7K. The 14.7K protects adenovirus-infected cells against cytolysis by tumor necrosis factor (TNF). TNF is a pleiotropic immunoregulatory protein that has anti-viral properties and is believed to provide a defense against virus infections. The 14.7K presumably counteracts the anti-viral effects of TNF in vivo. The mechanism of action of the 14.7K is unknown. Further studies on gp19K and 14.7K should assist our understanding of the immune system and adenovirus pathogenesis.
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PMID:Adenovirus region E3 proteins that prevent cytolysis by cytotoxic T cells and tumor necrosis factor. 253 58

Receptor tyrosine kinases (RTKs) are grouped into subcategories based on shared sequence and structural features. Human group C adenoviruses down-regulate EGF receptors, which are members of the class I family of RTKs, during the early stages of infection. Adenovirus appears to utilize a nonsaturable intracellular pathway since it causes EGF-R down-regulation even in cells that significantly overexpress EGF-R. Adenovirus-induced down-regulation is mediated by a small hydrophobic molecule coded for by the E3 early transcription region that has recently been localized to plasma membrane. Here we examine intracellular trafficking of other RTKs in adenovirus-infected cells, to better understand the molecular basis for the action of the E3 protein. Although p185c-neu, which is a class I RTK closely related to the EGF receptor, is down-regulated in cells expressing physiological concentrations of this molecule, it is not down-regulated in tumor cell lines that significantly overexpress p185c-neu. Cell surface receptors for insulin and IGF1, which are class II RTKs, are also reduced in cells expressing the E3 protein, although to a slightly lesser extent than the EGF receptor. Moreover, whereas EGF receptors are degraded between 3- and 9-h postinfection, insulin and IGF1 receptors are degraded between 6- and 12-h postinfection under identical conditions. In contrast to the class I and class II RTKs, there is no difference in the expression of the class III receptors for PDGF and aFGF in cells infected with a virus with an intact E3 region versus a virus mutant with an internal deletion in the relevant E3 gene. These results suggest that the E3 protein provides an internalization and degradative sorting signal for some class I and class II RTKs, although down-regulation of class II RTKs is somewhat less efficient. Molecular recognition of class I and class II RTKs during adenovirus infection may not be due strictly to amino acid structure, however, since EGF-R but not p185c-neu is down-regulated in cells where it is significantly overexpressed.
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PMID:Structurally related class I and class II receptor protein tyrosine kinases are down-regulated by the same E3 protein coded for by human group C adenoviruses. 809 18

Adenovirus encodes multiple gene products that regulate proapoptotic cellular responses to viral infection mediated by both the innate and adaptive immune systems. The E3-10.4K and 14.5K gene products are known to modulate the death receptor Fas. In this study, we demonstrate that an additional viral E3 protein, 6.7K, functions in the specific modulation of the two death receptors for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). The 6.7K protein is expressed on the cell surface and forms a complex with the 10.4K and 14.5K proteins, and this complex is sufficient to induce down-modulation of TRAIL receptor-1 and -2 from the cell surface and reverse the sensitivity of infected cells to TRAIL-mediated apoptosis. Down-modulation of TRAIL-R2 by the E3 complex is dependent on the cytoplasmic tail of the receptor, but the death domain alone is not sufficient. These results identify a mechanism for viral modulation of TRAIL receptor-mediated apoptosis and suggest the E3 protein complex has evolved to regulate the signaling of selected cytokine receptors.
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PMID:Three adenovirus E3 proteins cooperate to evade apoptosis by tumor necrosis factor-related apoptosis-inducing ligand receptor-1 and -2. 1105 95