Induction and protective effect of innate interferons during human astrovirus infection (VIR1P.1003)

Abstract

Abstract Members of the relatively new Astroviridae family are non-enveloped, single-stranded RNA viruses that cause diarrheal disease in a wide range species. Human astroviruses, of which there are eight canonical strains, are a leading cause of gastroenteritis in children <2 years old, the elderly, and immunocompromised patients. Because of the lack of a small animal model of astroviral gastroenteritis, little is known about the host response to infection. The role of type I and type III interferons (IFN), IFN-α/β and IFN-λ respectively, in mediating innate antiviral immune responses through a STAT1-dependent mechanism have been well established. Using human astrovirus type 1 (HAstV-1), the most common serotype isolated from human cases of gastroenteritis, we investigated the innate IFN response to astrovirus in cultured colonic epithelial cells (Caco2). HAstV-1 induced modest levels of IFN-β in Caco2 cells by 24 hours post-infection. Pre-treatment of cells with IFN-β protected Caco2 cells from HAstV-1 infection in a dose-dependent manner. Further, viral titers were significantly elevated in the presence of a neutralizing antibody to IFN-β. These data are in contrast to IFN-λ, which is induced by HAstV-1 to levels approximately 10-fold greater than those of IFN-β. However, IFN-λ pretreatment was not protective. Consistent with this, IFN-λ treatment did not induce STAT1 phosphorylation, suggesting that Caco2 cells are not responsive to IFN-λ.