UR 892 Inra, Unité de virologie et immunologie moléculaires, Domaine de Vilvert, 78352 Jouy-en-Josas, France, Hôpital Saint-Louis, Service de recherches en hémato-immunologie, UMR-E, Université Paris-VII, IUH, Paris, France, CEA, I2BM, Paris, France
Influenza is one of the most common infectious diseases in humans occurring as seasonal epidemic and sporadic pandemic outbreaks. The ongoing infections of humans with avian H5N1 influenza A viruses (IAV) and the ongoing pandemic caused by recently emerged swine-origin H1N1 viruses highlights the permanent threat caused by these viruses. Tropism and virulence of influenza is determined by host cellular proteases. In addition to the direct proteolytic cleaveage of viral proteins, proteases can also participate in the pathogenicity of influenza through the activation of a family of receptors called Protease-Activated Receptors. This review summarizes the role of proteases and their receptors in the virulence of influenza viruses, focusing on two families of proteases receptors (Annexin II and PAR-2) that represent a major therapeutic interest in fighting against viral infections. Finally, a better understanding of IAV-host cell interactions as well as immune responses against IAV is required for the development of more efficient means of prevention and treatment of influenza. In light of this observation, this review also highlights the more recent evidence suggesting that the nonclassical human leukocyte antigen (HLA-G) molecule is important to control the host immune response during infection.