Isolation of a Common Receptor for Coxsackie B Viruses and Adenoviruses 2 and 5

Abstract

A complementary DNA clone has been isolated that encodes a coxsackievirus and adenovirus receptor (CAR). When transfected with CAR complementary DNA, nonpermissive hamster cells became susceptible to coxsackie B virus attachment and infection. Furthermore, consistent with previous studies demonstrating that adenovirus infection depends on attachment of a viral fiber to the target cell, CAR-transfected hamster cells bound adenovirus in a fiber-dependent fashion and showed a 100-fold increase in susceptibility to virus-mediated gene transfer. Identification of CAR as a receptor for these two unrelated and structurally distinct viral pathogens is important for understanding viral pathogenesis and has implications for therapeutic gene delivery with adenovirus vectors.

Effects of bronchopulmonary inflammation induced by Pseudomonas aeruginosa on adenovirus-mediated gene transfer to airway epithelial cells in mice

“…37 Therefore, viral surface proteins or their cellular surface receptor(s) may undergo proteolysis by neutrophil elastase and/or damage by oxidants in secretions of infected airways. These proteins include the fiber protein of the viral capsid and its receptors on host cells, 38 including the recently described coxsackievirus and adenovirus receptor (CAR) 39 and the alpha-2 domain of major histocompatibility (MHC) class I, 40 in addition to the penton base complex of viral capsid and the ␣ v ␤3 and ␣ v ␤5 integrins on the host cell membrane. 41 Of further interest is the observation that P. aeruginosa has been found to upregulate the expression of the mucin gene MUC 2.…”

An interaction between penton base and αv integrins plays a minimal role in adenovirus-mediated gene transfer to hepatocytes in vitro and in vivo

“…Such studies have established the importance of interactions between the viral fiber and penton base proteins, and the fiber receptors [9][10][11][12] and ␣v integrins 13-17 on the cell surface. However, there is less knowledge about the importance of these interactions in cells that are targets for gene therapy.…”

“…First, the adenovirus fiber protein recognizes a receptor on the cell membrane. [9][10][11][12] Second, viral penton base binds to ␣v␤3 or ␣v␤5 integrins. 13,14 The interaction of penton base with cell surface integrins is thought to have several effects.…”

Dual targeting of gene delivery by genetic modification of adenovirus serotype 5 fibers and cell-selective transcriptional control

“…This is particularly important for cell types that have low or negligible coxsackie and adenovirus receptor (CAR) or heparan sulfate proteoglycans (HSPG) expression, the primary receptors for Ad 5 and AAV-2, respectively. [10][11][12] It is important to note, however, that vectors modified in this manner are not selective and can transduce a wide repertoire of cell types. In fact, RGD-modified vectors were originally developed to broaden the tropism of Adbased vectors.…”