John Schoggins, Ph.D.

One of the viruses that causes seasonal flu is called influenza A virus. This virus is transmitted from person to person through air droplets, for example through sneezing or coughing. The virus then enters the respiratory tract, where it encounters numerous different cell types. One cell type critical for controlling influenza virus is the alveolar macrophage. Without these cells, influenza causes severe disease. We will study how alveolar macrophages help keep influenza in check, and how genetic modification of alveolar macrophages affect the ability of influenza to cause disease. We will use mouse models in which we have genetically altered the alveolar macrophages so that they cannot be infected easily with the influenza virus. These studies have the potential to reveal new avenues for the development of anti-flu therapies.

Update:

The mammalian protein LY6E is emerging as an important host factor with diverse roles in viral infection. We previously showed that LY6E helps promote influenza A virus infection in cultured cells. In more recent studies, we discovered that LY6E has the opposite effect on coronaviruses—it functions as a restriction factor to inhibit fusion of coronaviruses with cells. This includes the recently emerged SARS-CoV-2, which causes COVID-19. Thus, for two distinct classes of respiratory viruses, Ly6e has opposing effects in viral entry. We are currently examining how Ly6e impacts these viruses using mouse models in which Ly6e has been genetically modified.