A New Link Between Virus Cell Entry and Inflammation: Adenovirus Interaction With Integrins Induces Specific Proinflammatory Responses

Abstract

Replication-defective or conditionally replicating human adenoviral (HAdV) vectors have shown considerable promise as gene or vaccine delivery vehicles, particularly for the treatment of cardiovascular diseases or cancer. Nevertheless, the propensity of HAdV vectors to elicit a robust proinflammatory response following systemic administration limits their use in the clinic.1 As a result of the potential severity of virus-induced inflammation and accompanying toxicity,2 the majority of HAdV-mediated gene delivery studies have used local rather than systemic delivery of the viral vector. For example, the efficiency of HAdV-mediated gene delivery has been evaluated following direct injection into a tumor mass3 or into the confined spaces of certain organs such as the bladder4 so as to limit exposure of the viral vector to immune cells that mediate cytokine production. However, the disadvantage of local injection is that vector spread throughout the target tissues is often suboptimal. Furthermore, local administration of HAdV vectors is not intended to reach distant sites in the body that may contain migrating tumor cells. Thus, to exploit the advantages of systemic HAdV administration, it will be necessary to obtain a better understanding of how this virus provokes host inflammatory responses.