Astroviruses are nonenveloped, positive-sense single-stranded RNA viruses that cause gastrointestinal illness. Although a leading cause of pediatric diarrhea, human astroviruses are among the least characterized enteric RNA viruses. However, by using in vitro methods and animal models to characterize virus-host interactions, researchers have discovered several important properties of astroviruses, including the ability of the astrovirus capsid to act as an enterotoxin, disrupting the gut epithelial barrier. Improved animal models are needed to study this phenomenon, along with the pathogenesis of astroviruses, particularly in those strains that can cause extraintestinal disease. Much like for other enteric viruses, the current dogma states that astroviruses infect in a species-specific manner; however, this assumption is being challenged by growing evidence that these viruses have potential to cross species barriers. This review summarizes these remarkable facets of astrovirus biology, highlighting critical steps toward increasing our understanding of this unique enteric pathogen.

Astroviruses are a major cause of diarrhea in the young, elderly, and the immunocompromised. Since the discovery of human astrovirus type 1 (HAstV-1) in 1975, the family Astroviridae has expanded to include two more human clades and numerous mammalian and avian-specific genotypes. Despite this, there is still little known about pathogenesis. The following review highlights the current knowledge of astrovirus pathogenesis, and outlines the critical steps needed to further astrovirus research, including the development of animal models of cell culture systems.

Astroviruses (AstV) are a leading cause of diarrhea, especially in the very young, the elderly, and immunocompromised populations. Despite their significant impact on public health, no drug therapies for astrovirus have been identified. In this study, we fill this gap in knowledge and demonstrate that the FDA-approved broad-spectrum anti-infective drug nitazoxanide (NTZ) blocks astrovirus replication in vitro with a 50% effective concentration (EC50) of approximately 1.47 μM. It can be administered up to 8 h postinfection and is effective against multiple human astrovirus serotypes, including clinical isolates. Most importantly, NTZ reduces viral shedding in vivo, exhibiting its potential as a future clinical therapeutic. IMPORTANCE Human astroviruses (HAstV) are thought to cause between 2 and 9% of acute, nonbacterial diarrhea cases in children worldwide. HAstV infection can be especially problematic in immunocompromised people and infants, where the virus has been associated with necrotizing enterocolitis and severe and persistent diarrhea, as well as rare instances of systemic and fatal disease. And yet, no antivirals have been identified to treat astrovirus infection. Our study provides the first evidence that nitazoxanide may be an effective therapeutic strategy against astrovirus disease.