Binding Properties, Cell Delivery, and Gene Transfer of Adenoviral Penton Base Displaying Bacteriophage

Giovine, Monica Di; Salone, B.; Martina, Yuri; Amati, Viviana; Zambruno, Giovanna; Cundari, Enrico; Failla, Cristina Maria; Saggio, Isabella

doi:10.1006/viro.2000.0809

Cited by 50 publications

(35 citation statements)

References 38 publications

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“…A previous study showed that a filamentous phage displaying the full-length Ad2 penton base bound more efficiently to ␣3␤1 than a phage displaying only the region spanning residues 286 to 392 (4). Considering that both RGD and LDV motifs are included in the residue 286-to-392 fragment, this result suggests that other amino acid residues may be implicated in the interaction between Ad and the ␣3␤1 integrin.…”

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confidence: 81%

“…For this purpose, we analyzed the binding of adenovirions and recombinant penton base to HeLa and SCC-25 human cell lines, which are known to express ␤1 integrins. HeLa cells also display CAR receptors but are poor in ␣v␤3 and ␣v␤5 integrin subtypes (4,18). The tongue squamous-cell carcinoma-derived cell line SCC-25 is characterized by high levels of ␣2␤1 and ␣3␤1 integrins but displays low levels of CAR, ␣v␤3, and ␣v␤5 receptors (18).…”

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confidence: 99%

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Integrinα3β1 Is an Alternative Cellular Receptor for AdenovirusSerotype5

Salone

Martina

Piersanti

et al. 2003

J Virol

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Many adenovirus serotypes enter cells by high-affinity binding to the coxsackievirus-adenovirus receptor (CAR) and integrin-mediated internalization. In the present study, we analyzed the possible receptor function of ␣3␤1 for adenovirus serotype 5 (Ad5). We found that penton base and integrin ␣3␤1 could interact in vitro. In vivo, both Ad5-cell binding and virus-mediated transduction were inhibited in the presence of anti-␣3 and anti-␤1 function-blocking antibodies, and this occurred in both CAR-positive and CAR-negative cell lines. Peptide library screenings and data from binding experiments with wild-type and mutant penton base proteins suggest that the Arg-Gly-Asp (RGD) in the penton base protein, the best known integrin binding motif, is only part of the binding interface with ␣3␤1, which involved multiple additional contact sites.Adenovirus (Ad) host cell entry requires an initial attachment to cells which is mediated by the fiber interaction with the coxsackievirus-Ad receptor (CAR) (2). The subsequent association of the capsid protein penton base with integrin molecules promotes Ad entry (31). Integrins are a family of structurally and functionally related cell surface heterodimeric receptors that mediate cell migration and adhesion. The major extracellular ligands for integrins are collagens, laminins, fibronectin, tenascin, vitronectin, von Willebrand factor, and fibrinogen, reflecting the primary function of integrins in cell adhesion to the extracellular matrix. The ␣v␤1, -3, -5, -6, and -8 integrins, the ␣5␤1 and ␣8␤1 integrins, and the ␣IIb␤3 integrins form a subgroup that primarily recognizes ligands containing Arg-Gly-Asp (RGD) motifs (see reference 13 and references therein). Many microorganisms utilize integrins to gain entry into cells: the SA11 rotavirus binds to ␣2␤1 and ␣4␤1 (9), ␣v␤3 and ␣v␤1 integrins are receptors of the human parechovirus 1 (30), and ␣v␤5 has been proposed, although not conclusively, as a coreceptor in adeno-associated virus type 2 infection (27, 29). The foot-and-mouth disease virus uses different integrins for cell infection (14,15,16). Integrin ␣3␤1 is a cellular receptor for Kaposi's sarcoma-associated herpesvirus (1). Yersinia pseudotuberculosis binds to members of the ␤1 integrin family in order to enter eukaryotic cells (22).Several Ad serotypes contain an RGD motif in the penton base protein. This feature, and the Ad cell-detaching property, suggested an interaction of the virus with the integrin receptors. Indeed, ␣v␤3 and ␣v␤5 are receptors for human Ad2 and Ad5, and direct binding to isolated ␣v␤5 was shown for human Ad2, Ad3, Ad4, Ad5, and Ad37 (24, 31). In hematopoietic and melanoma cells, respectively, the ␣M␤2 and b1 integrins were found to be implicated in human Ad5 infection (3, 12). More recent evidence indicates ␣v␤1 as an Ad2 and Ad5 coreceptor in the human embryonic kidney (HEK293) cell line (23). Ad interaction with the ␣v␤1, -3, and -5 integrin subtypes is efficiently competed by RGD-containing peptides (23, 31). A second integrin binding motif is...

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confidence: 81%

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confidence: 99%

Integrinα3β1 Is an Alternative Cellular Receptor for AdenovirusSerotype5

Salone

Martina

Piersanti

et al. 2003

J Virol

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“…However, despite some apparent advantages over eukaryotic viruses, tissue-targeted phage virions have shown limited efficacy as bacteriophage has evolved to infect bacteria only and has no optimized strategy to express transgenes upon entry into eukaryotic cells (5). To overcome this limitation, a new generation of hybrid prokaryotic-eukaryotic viral vectors was recently reported (9).…”

Section: Adeno-associated Virus/phage (Aavp) Is a Gene Delivery Vectomentioning

confidence: 99%

Clathrin-mediated Endocytosis and Subsequent Endo-Lysosomal Trafficking of Adeno-associated Virus/Phage

Stoneham

Hollinshead

Hajitou

2012

Journal of Biological Chemistry

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“…The other population of phages recovered after cell lysis corresponded to intracellular phages. It has been shown that recombinant bacteriophages carrying a portion of the Ad penton base sequence overlapping the RGD peptide motif were capable of binding to ␣v integrins of the mammalian-cell plasma membrane and were found to be endocytosed into endosomal vesicles (10). We then postulated that intracellular phage recovered from CF-KM4 cells were competent for cell entry and that this novel competency, conferred upon the bacteriophages by the extrinsic peptides displayed on their pIII attachment proteins, could also be conferred upon recombinant Ad vectors by insertion of the same peptides into their fibers.…”

Section: Screening For Peptide Ligands Of Cell Internalization Receptmentioning

confidence: 99%

Gene Transduction and Cell Entry Pathway of Fiber-Modified Adenovirus Type 5 Vectors Carrying Novel Endocytic Peptide Ligands Selected on Human Tracheal Glandular Cells

Gaden

Franqueville

Magnusson³

et al. 2004

J Virol

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Monolayers of cystic fibrosis transmembrane conductance regulator (CFTR)-deficient human tracheal glandular cells (CF-KM4) were subjected to phage biopanning, and cell-internalized phages were isolated and sequenced, in order to identify CF-KM4-specific peptide ligands that would confer upon adenovirus type 5 (Ad5) vector a novel cell target specificity and/or higher efficiency of gene delivery into airway cells of patients with cystic fibrosis (CF). Three different ligands, corresponding to prototypes of the most represented families of phagotopes recovered from intracellular phages, were designed and individually inserted into Ad5-green fluorescent protein (GFP) (AdGFP) vectors at the extremities of short fiber shafts (seven repeats [R7]) terminated by scissile knobs. Only one vector, carrying the decapeptide GHPRQMSHVY (abbreviated as QM10), showed an enhanced gene transduction of CF-KM4 cells compared to control nonliganded vector with fibers of the same length (AdGFP-R7-knob). The enhancement in gene transfer efficiency was not specific to CF-KM4 cells but was observed in other mammalian cell lines tested. The QM10-liganded vector was referred to as AdGFP-QM10-knob in its knobbed version and as AdGFP-QM10 in its proteolytically deknobbed version. AdGFP-QM10 was found to transduce cells with a higher efficiency than its knob-bearing version, AdGFP-QM10-knob. Consistent with this, competition experiments indicated that the presence of knob domains was not an absolute requirement for cell attachment of the QM10-liganded vector and that the knobless AdGFP-QM10 used alternative cell-binding domains on its capsid, including penton base capsomer, via a site(s) different from its RGD motifs. The QM10-mediated effect on gene transduction seemed to take place at the step of endocytosis in both quantitative and qualitative manners. Virions of AdGFP-QM10 were endocytosed in higher numbers than virions of the control vector and were directed to a compartment different from the early endosomes targeted by members of species C Ad. AdGFP-QM10 was found to accumulate in late endosomal and low-pH compartments, suggesting that QM10 acted as an endocytic ligand of the lysosomal pathway. These results validated the concept of detargeting and retargeting Ad vectors via our deknobbing system and redirecting Ad vectors to an alternative endocytic pathway via a peptide ligand inserted in the fiber shaft domain.Viruses have developed natural strategies to infect and grow in specific tissues of particular hosts, and their specificity and restricted host range make them theoretically the best-adapted vectors to transfer therapeutic genes into recipient cells that are their natural targets. However, when desired cell targets are not part of the natural host range of the virus, genetic modifications are required to adapt the virus and its derived vectors to these novel hosts. Since viral tropism is, in large part, under the control of primary virus-cell interaction occurring at the cell surface, the most obvious modification consists of...

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Binding Properties, Cell Delivery, and Gene Transfer of Adenoviral Penton Base Displaying Bacteriophage

Cited by 50 publications

References 38 publications

Integrinα3β1 Is an Alternative Cellular Receptor for AdenovirusSerotype5

Integrinα3β1 Is an Alternative Cellular Receptor for AdenovirusSerotype5

Clathrin-mediated Endocytosis and Subsequent Endo-Lysosomal Trafficking of Adeno-associated Virus/Phage

Gene Transduction and Cell Entry Pathway of Fiber-Modified Adenovirus Type 5 Vectors Carrying Novel Endocytic Peptide Ligands Selected on Human Tracheal Glandular Cells

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