Pathogenesis of influenza virus infections: the good, the bad and the ugly

The clinical outcome of different influenza virus infections ranges from subclinical upper respiratory tract disease to fatal lower respiratory tract disease. An important determinant in the pathogenesis of these diseases is the tissue tropism of the influenza virus. Furthermore, virulence is often correlated with virus replication and is regulated by multiple virus genes. Host defense against virus infection consists of both innate and adaptive immune responses. However, excessive or dysbalanced immune response may result in lung tissue damage, reduced respiratory capacity, and severe disease or even death. By interdisciplinary efforts to better understand the intricate interaction between virus, tissue, and immune response, we may be able to find new ways to improve the outcome of influenza virus infections.

► Tropism for upper or lower respiratory tract is a major determinant for the outcome of influenza virus infections and transmission. ► Virulence of influenza viruses is a polygenic viral trait. ► Pre-existing homosubtypic and heterosubtypic immunity to influenza viruses can have a major impact on the outcome of influenza virus infection. ► Host factors can contribute to the pathogenesis of influenza virus infections and may deteriorate the outcome of infections.