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Query: UMLS:C0001486 (Adenovirus)
 3,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Viruses are multivalent particles that attach to cells through one or more bonds between viral attachment proteins (VAP) and specific cellular receptors. Three modes of virus binding are presented that can explain the diversity in binding data observed among viruses. They are based on multivalency of attachment and spatial versus receptor saturation effects which are easily distinguished based upon simple criteria. Mode 1 involves only monovalent virus/receptor binding. Modes 2 and 3 involve multivalent bonds between the virus and cell; however, in mode 3 space on the cell surface becomes saturated before receptors. A model is developed for viral attachment that accounts for nonspecific binding, receptor/virus interactions, and spatial saturation effects. The model can describe each mode in different limits and can be applied to virus binding data to extract key physical information such as receptor number and affinity. These values are used to postulate the type of VAP/receptor interaction involved and to predict binding at different parameter values. For the mode 2 binding of Adenovirus 2, the model predicts a receptor number of 4-15 x 10(3) on HeLa cells and an affinity of 2-6 x 10(7) M-1 which closely approximate experimental estimates. For the binding of three, broad-host-range, enveloped viruses, Semliki Forest virus, Vesicular Stomatitis virus, and the baculovirus, Autographa californica nuclear polyhedrosis virus, the model predicts receptor numbers of 10(5) or greater and affinities in the range of 10(4) to 10(5) M-1. These values are indicative of a VAP/oligosaccharide interaction which has been documented for a number of other viruses. Experimental evidence is presented that is the first to demonstrate that baculovirus binding is mediated by a cell surface receptor.
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PMID:General analysis of receptor-mediated viral attachment to cell surfaces. 217 56

Adenoviruses have been previously shown to enhance the delivery of many ligands including proteins and plasmid DNAs to the cells. The key biochemical step during this process is the ability of adenovirus to disrupt (lyse) the endosome membrane releasing the co-internalized virus and the other ligands into the cytosol (Seth et al, 1986, In: Adenovirus attachment and entry into cells, pp 191-195, American Society for Microbiology, Washington, D.C.). To understand the role of the adenovirus proteins involved in the endosome lysis, it is further shown here that empty capsids of adenovirus also possess this membrane vesicle lytic activity; though the activity is about 5-times lower than the adenovirus. Incubation of adenovirus with low concentration of ionic detergent or brief exposure to 45 degrees C destroyed this lytic activity without affecting the adenovirus binding to cell surface receptor, suggesting the lytic activity of adenovirus to be of enzymatic nature. However, exposing adenovirus to conditions that can disrupt adenovirus capsid structure such as heating at 65 degrees C, treating with 0.5% SDS, treating with different proteases, dialyzing against no glycerol buffer, treating with 6 M urea or with 10% pyridine, and sonication destroyed the adenovirus-associated lytic activity. Results suggest the requirement of an intact capsid structure for adenovirus-mediated lysis of the endosome.
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PMID:Mechanism of adenovirus-mediated endosome lysis: role of the intact adenovirus capsid structure. 780 64

Group B coxsackieviruses are etiologically linked with many human diseases including acute myocarditis and associated chronic dilated cardiomyopathy. Well-established CVB3 cardiovirulent strains (CVB3c(s)) with known phenotypic difference have been used to study the pathogenesis of virus-induced heart disease. The receptor-binding characteristics of cardiovirulent CVB3 are not known, but may represent one mechanism accounting for differences in disease virulence. In this study, interactions between CVB3c(s) and the decay-accelerating factor (DAF or CD55) cell surface receptor were examined. Anti-DAF monoclonal antibodies (MAbs) blocked virus binding and infection of susceptible HeLa cells. Virus binding was significantly reduced by treatment of these cells with phosphatidylinositol phospholipase C enzyme, which rendered them DAF-deficient CVB3c(s) exhibited a differential propensity for the DAF receptor, as several cardiovirulent strains interacted more strongly than others. However, virus binding and infection was always most effectively blocked by MAbs directed against the SCR 2 and 3 domains of DAF, suggesting that binding occurs at a similar site(s) on the molecule for all strains. Virus binding and internalization were associated with DAF down-regulation at the cell surface, as monitored by flow cytometry analysis. Cardiovirulent CVB3 did not interact with molecules functionally and/or structurally related to DAF, including CD35, CD46, Factor H, or C4-binding protein. Adenovirus type 2 (Ad2) does not use the DAF receptor. However, competitive binding assays between Ad2 and CVB1-6, CVB3c(s), anti-DAF MAbs, or DAF-reduced cells indicated that DAF is associated with Ad2 receptors on the HeLa cell membrane. In summary, this study indicates that DAF is an attachment receptor for cardiovirulent CVB3 and that DAF interaction may be important in the pathogenesis of CVB-mediated heart disease.
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PMID:Cardiovirulent coxsackieviruses and the decay-accelerating factor (CD55) receptor. 960 1

Studies in cultured cell lines have shown that adenovirus infection involves binding of adenovirus fiber to its cell surface receptor and binding of penton base to alpha v integrins. However, much less is known about the role of these interactions in cells that are targets for adenovirus-mediated gene transfer. Earlier work showed that hepatocytes are readily infected by adenovirus, making them an attractive target for gene therapy in several diseases. We found that addition of fiber protein blocked adenovirus infection of primary cultures of hepatocytes. This suggests an important role for fiber and its receptor. However, mutation of the integrin-binding motif in penton base did not inhibit infection of hepatocytes, even though the mutation impaired infection of HeLa cells. Hepatocytes had undetectable amounts of alpha v integrins on their cell surface and showed no specific adherence to vitronectin, the natural substrate of alpha v integrins. Adenovirus with an intact penton base enhanced infection of liver following intravenous injection, but only by three-fold as compared with virus in which the integrin-binding motif was disrupted. These studies suggest that interactions between cell surface integrins and penton base are not required for adenovirus infection of hepatocytes in vitro, but the interaction enhances infection to a small degree in vivo.
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PMID:An interaction between penton base and alpha v integrins plays a minimal role in adenovirus-mediated gene transfer to hepatocytes in vitro and in vivo. 993 Mar 28

Adenovirus (Ad) entry into cells is initiated by the binding of the fiber knob to a cell surface receptor. The coxsackie- and adenovirus receptor (CAR) functions as the attachment receptor for many, but not all, Ad serotypes. Ad type 37 (Ad37), a subgroup D virus that causes keratoconjunctivitis in humans, does not infect cells via CAR despite demonstrated binding of the Ad37 knob to CAR. We have pseudotyped a fiber deletion Ad5 vector with the Ad37 fiber (Ad37f), and this vector retains the ocular tropism of Ad37. Here we present a cryo-electron microscopy reconstruction of Ad37f that shows the entire Ad37 fiber, including the shaft and knob domains. We have previously proposed that Ad37 may not utilize CAR for cell entry because of the geometric constraints imposed by a rigid fiber (E. Wu, J. Fernandez, S. K. Fleck, D. Von Seggern, S. Huang, and G. R. Nemerow, Virology 279:78-89, 2001). Consistent with this hypothesis, our structural results show that the Ad37 fiber is straight and rigid. Modeling of the interaction between Ad37f and host cell receptors indicates that fiber flexibility or rigidity, as well as length, can affect receptor usage and cellular tropism.
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PMID:Structural analysis of a fiber-pseudotyped adenovirus with ocular tropism suggests differential modes of cell receptor interactions. 1133 20

Adenovirus-based gene therapy may provide an alternative mode of treatment for prostate cancer, especially for late-stage and androgen-independent disease for which there is currently no effective treatment. Efficient adenovirus infection of target cells depends upon the presence of the coxsackie adenovirus cell surface receptor, CAR, which is the primary receptor for group C adenoviruses and is important for the attachment of adenovirus to the cell membrane. To evaluate the potential efficacy of adenoviral therapy for prostate cancer, we evaluated CAR expression in normal prostate tissue and in prostate carcinoma of increasing Gleason grades in paraffin-embedded, archival tissues using a polyclonal antibody raised against human CAR. Immunohistochemical analysis of benign prostate epithelia demonstrated intense luminal and lateral cell membrane staining. There was a statistically significant difference in CAR membrane expression with respect to Gleason score. In addition, metastatic prostate specimens demonstrated strong membrane staining for CAR. Adenovirus therapy may, therefore, provide an alternate modality in the treatment of prostate cancer and may be especially efficacious in the treatment of metastatic disease.
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PMID:Expression of the coxsackie adenovirus receptor in normal prostate and in primary and metastatic prostate carcinoma: potential relevance to gene therapy. 1209 94