Adenoviral Infection

The knowledge of adenovirus infection provides the basics for the development of adenoviral retargeting strategies. The native adenoviral infection pathway starts with the adherence of the virus to the cell surface for which two cellular receptors are responsible. As shown in Fig. 1, the initial binding of the subtype C adenoviruses, like Ad type 5/2, on the cell is mediated by attachment of the adenoviral fiber-knob region (the distal tip of each fiber monomer) onto CAR (2,3). This cell surface protein has two immunoglobulin-like domains in its extracellular region (22). It, thus, has been suggested that it plays a role in cell-cell junction (23,24), but its complete function has not been fully elucidated yet. After binding to the cell surface via CAR, receptor-mediated endocytosis of the virion requires a second step that involves the interaction of Arg-Gly-Asp (RGD) motifs in the penton base with the surface integrins av^3 or avP525. The viral entry is followed by a stepwise disassembly of the virus in the endosome and the consecutive endosomal lysis, which is mediated by the penton base and low

Fig. 1. Mechanism of adenoviral infection. Initial binding of adenovirus to cells is mainly mediated by the interaction between the adenoviral fiber-knob region and the CAR on the surface of the cells. Subsequently, the RGD motif in the viral penton base region binds to integrins on the cell, inducing internalization of the virus. Stepwise disassembly in the endosome, and then endosomal lysis mediated by the penton base and low endosomal pH release the capsid into the cytosol, followed by transportation to the nucleus and finally viral DNA release.

Fig. 1. Mechanism of adenoviral infection. Initial binding of adenovirus to cells is mainly mediated by the interaction between the adenoviral fiber-knob region and the CAR on the surface of the cells. Subsequently, the RGD motif in the viral penton base region binds to integrins on the cell, inducing internalization of the virus. Stepwise disassembly in the endosome, and then endosomal lysis mediated by the penton base and low endosomal pH release the capsid into the cytosol, followed by transportation to the nucleus and finally viral DNA release.

intraendosomal pH. After the release of the capsid into the cytosol, it is transported to the cell nucleus where theviral DNA is released (26). Because viral entry and endosomal escape are independent phenomena, modification of the viral binding capability would not compromise downstream events.

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