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)

Adenovirus (Ad) infection is concluded by assembly of virions in the cell nucleus followed by lysis of cells by an unknown mechanism. We have described an Ad nuclear membrane glycoprotein of 11,600 kDa (E3-11.6K) which is encoded by the E3 transcription unit and which is synthesized in small amounts from the E3 promoter at early stages of infection but in large amounts from the major late promoter at very late stages of infection. We now report that E3-11.6K is required for the efficient lysis (death) of Ad-infected cells, and we propose that the function of E3-11.6K is to mediate the release of Ad progeny from infected cells. We have renamed E3-11.6K the Ad death protein (ADP). Virus mutants that lack ADP replicated as well as adp+ Ad, but the cells lysed more slowly, virus release from the cell was retarded, and the plaques were small and developed slowly. Cells infected with adp+ viruses began to lyse at 2 or 3 days postinfection (p.i.) and were completely lysed by 5 or 6 days p.i. In contrast, cells infected with adp mutants did not begin significant lysis until 5 or 6 days p.i. Cell lysis and viability were determined by plaque size, extracellular virus, cell morphology, release of lactate dehydrogenase, trypan blue exclusion, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay for mitochondrial activity, RNA degradation, and DNA degradation as determined by agarose gel electrophoresis and the terminal deoxynucleotidyltransferase end labeling assay. Protein synthesis was almost nonexistent at 3 days p.i. in cells infected with adp+ Ads, but it was still increasing in cells infected with adp mutants. Host cell protein synthesis was undetectable at 1 day p.i. in cells infected with adp+ Ads or adp mutants. Cells infected with adp mutants showed Ad cytopathic effect at 1 or 2 days p.i. in that they rounded up and detached, but the cells remained metabolically active and intact for >5 days p.i. When examined by electron microscopy, the nuclei were extremely swollen and full of virus, and the nuclear membrane appeared to be intact. ADP is unrelated in sequence to other known cell death-promoting proteins.
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PMID:The adenovirus death protein (E3-11.6K) is required at very late stages of infection for efficient cell lysis and release of adenovirus from infected cells. 864 56

Homeostasis of cell numbers in tissues is maintained by a critical balance between cell proliferation and programmed cell death or apoptosis. Many human viruses are able to develop suitable strategies for modifying apoptosis in virus-infected cells and in virus-primed T cells. Apoptosis is characterized by the fragmentation of nuclear DNA into 180-200 bp apoptotic bodies and can be analysed microscopically or by flow cytometry using staining with various dyes. Moreover DNA cleavage can be identified by electrophoresis and by specific labeling using in situ nucleotidyltransferase assay (ISNT), terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling technique (Tunel), or by Elisa. Adenovirus E1A induces expression of protooncogenes c-myc and c-fos which sensitize cells to apoptosis; EBV EBNA-5, and adenovirus E1A, HPV E7, and polyomavirus large T act in the same way by displacing pRB-bound E2F. EBV EBNA-5, HPV E6, Adenovirus E1B 55 kDa inactivate the tumor suppressor protein p53 and engage the cells in the transformation process. EBV LMP-1, HHV6, and HTLV1 tax induce the antiapoptotic bcl-2 protein. EBV BHRF1 encodes proteins with homology to bcl-2 and Adenovirus E1B 19 kDa encodes proteins that have protective functions similar to bcl-2. Activated lymphocytes responding to viral infections express high levels of fas and are susceptible to apoptosis. TNF alpha can down- or up-regulate fas and down-regulates TNF-R. Adenovirus E1B 19 kDa blocks the proapoptotic activity of TNF alpha. Inversly, Cytomegalovirus, hepatitis C virus and Myxoviruses up-regulate fas antigen prior to undergoing apoptosis. In HIV-infected patients, CD4+ T-cell apoptosis is mediated by the cytopathic effect of the virus and the cell surface expression of gp 120-env protein. Moreover, an accelerated T-cell apoptosis in HIV-infected individuals is characterized by (i) HIV gp120-CD4+ cross-linking and subsequent aberrant signaling of T-cells, (ii) involvement of TNF alpha-fas/Apo-1 (TNF-R) binding, (iii) involvement of accessory cells as an apoptosis inducer and as a result of defective antigen presentation, (iv) possible superantigen activity induced by HIV products and cofactors. Many viruses also encode proteins with protease activity which could induce apoptosis. The induction of apoptosis may result in virus clearance, in contrast the inhibition of apoptosis may result in virus cell transformation and viral persistence. Indirectly, the apoptosis of infected cells may be induced by CTLs, NK cells and cytokines. In addition, apoptosis-mediated physiological depletion of T lymphocytes in the course of viral infection can silence the immune response and can induce immunodeficiency.
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PMID:[Apoptosis and human viral infections]. 886 58

Adenovirus-transduced CD34+ cells expressing membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (CD34-TRAIL+ cells) exert potent antitumor activity. To further investigate the mechanism(s) of action of CD34-TRAIL+ cells, we analyzed their homing properties as well as antitumor and antivascular effects using a subcutaneous myeloma model in immunodeficient mice. After intravenous injection, transduced cells homed in the tumor peaking at 48 hours when 188 plus or minus 25 CD45+ cells per 10(5) tumor cells were detected. Inhibition experiments showed that tumor homing of CD34-TRAIL+ cells was largely mediated by vascular cell adhesion molecule-1 and stromal cell-derived factor-1. Both CD34-TRAIL+ cells and soluble (s)TRAIL significantly reduced tumor volume by 40% and 29%, respectively. Computer-aided analysis of TdT-mediated dUTP nick end-labeling-stained tumor sections demonstrated significantly greater effectiveness for CD34-TRAIL+ cells in increasing tumor cell apoptosis and necrosis over sTRAIL. Proteome array analysis indicated that CD34-TRAIL+ cells and sTRAIL activate similar apoptotic machinery. In vivo staining of tumor vasculature with sulfosuccinimidyl-6-(biotinamido) hexanoate-biotin revealed that CD34-TRAIL+ cells but not sTRAIL significantly damaged tumor vasculature, as shown by TdT-mediated dUTP nick end-labeling+ endothelial cells, appearance of hemorrhagic areas, and marked reduction of endothelial area. These results demonstrate that tumor homing of CD34-TRAIL+ cells induces early vascular disruption, resulting in hemorrhagic necrosis and tumor destruction.
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PMID:Human CD34+ cells engineered to express membrane-bound tumor necrosis factor-related apoptosis-inducing ligand target both tumor cells and tumor vasculature. 2007 60