Laboratoire de virologie médicale et moléculaire, CHU de Reims, Avenir Inserm EA/ IFR53, faculté de médecine, avenue Koenig, 51100 Reims, Laboratoire P4 Jean-Mérieux-Inserm, Lyon
Human enteroviruses, which belong to the family of Picornaviridae, are common infectious viral agents transmitted by fecal-oral or airway routes. These positive RNA viruses possess a high genetic diversity and variability. They can evolve through genetic mutations or recombination mechanisms that are associated to the emergence of new potential epidemic serotypes. Human enteroviruses use different cellular receptors: receptors and co-receptors that are directly related to the tropism and the epidemiologic characteristics of some enterovirus serotypes. The receptors onto the cell-surface settle within a capsid depression, called canyon, initiating the process of viral uncoating. For some enteroviruses, a co-receptor molecule allows the crossing of cell topological barriers that is required to initiate the target cell infection. After the attachment phase, enteroviruses use the endocellar signaling pathways to support and optimize their entry into target-cells via endocytic pathways. The clathrin coated pits and the caveolae are both major ways of enterovirus entry in the cell even if “new” endocytic pathways regulated by enzymes of the ADP ribosylation factors family and of the Rho family small GTPases have been recently described. The viral genetic diversity allows the human enteroviruses to simultaneously or alternatively use several distinct endocytic pathways in accordance to the infected cell lines, and allows a rapid and efficient adaptation to cellular microenvironments and to multiple immune selection pressures developed during the pathophysiological course of human infection. In conclusion, entry mechanisms used by human enteroviruses to infect target cells are various but they are closely dependent on the cellular functions that will be driven towards viral benefits. In the present time, the attachment and entry phases of the human enteroviruses into the target cell represent major viral events that may be targeted for the development of further new antiviral strategies.