The pathogenesis of influenza virus infections: the contributions of virus and host factors

Abstract

Influenza viruses cause acute respiratory inflammation in humans and symptoms such as high fever, body aches, and fatigue. Usually these symptoms improve after several days; however, the 2009 pandemic H1N1 influenza virus [influenza A(H1N1) 2009] is more pathogenic than seasonal influenza viruses and the pathogenicity of highly pathogenic H5N1 viruses is still higher. The 1918 influenza pandemic virus caused severe pneumonia, resulting in an estimated 50 million deaths worldwide. Several virulence factors have been identified in these virus strains, but host factors are also responsible for the pathogenesis of infections caused by virulent viruses. Here, we review the contributions of both virus and host factors to the pathogenesis of these viral infections.

Figure

A model depicting the multi-cellular interactions that regulate the inflammatory response during influenza virus infection. Influenza virus infection induces innate immune responses mediated by the TLR7 and RIG-I signaling pathways. Pulmonary macrophages migrate to infected epithelial cells in an CCL2-CCR2-dependent manner and induce apoptosis in the respiratory epithelial cells via TRAIL-death receptor 5 (DR5) interactions. On the other hand, the interaction of CD200 and CD200R downregulates the inflammatory response, including IL-6 and TNFα production by macrophages. Effector CD8 T cells also inhibit the inflammatory response by IL-10. CD4 T cells and macrophages produce IL-2 and IL-27, respectively, to support the regulatory function of IL-10-producing effector CD8 T cells.