Noroviruses are a leading cause of gastroenteritis worldwide. Although infections in healthy individuals are self-resolving, immunocompromised individuals are at risk for chronic disease and severe complications. Chronic norovirus infections in immunocompromised hosts are often characterized by long-term virus shedding, but it is unclear whether this shed virus remains infectious. We investigated the prevalence, genetic heterogeneity, and temporal aspects of norovirus infections in 1140 patients treated during a 6-year period at a pediatric research hospital. Additionally, we identified 20 patients with chronic infections lasting 37 to >418 days. Using a new human norovirus in vitro assay, we confirmed the continuous shedding of infectious virus for the first time. Shedding lasted longer in male patients and those with diarrheal symptoms. Prolonged shedding of infectious norovirus in immunocompromised hosts can potentially increase the likelihood of transmission, highlighting the importance of isolation precautions to prevent nosocomial infections.

Since the 1970s, eight closely related serotypes of classical human astroviruses (HAstV) have been associated with gastrointestinal illness worldwide. In the late 2000s, three genetically unique human astrovirus clades, VA1-VA3, VA2-VA4, and MLB, were described. While the exact disease associated with these clades remains to be defined, VA1 has been associated with central nervous system infections. The discovery that VA1 could be grown in cell culture, supports exciting new studies aimed at understanding viral pathogenesis. Given the association of VA1 with often lethal CNS infections, we tested its susceptibility to the antimicrobial drug, nitazoxanide (NTZ), which we showed could inhibit classical HAstV infections. Our studies demonstrate that NTZ inhibited VA1 replication in Caco2 cells even when added at 12 h post-infection, which is later than in HAstV-1 infection. These data led us to further probe VA1 replication kinetics and cellular responses to infection in Caco-2 cells in comparison to the well-studied HAstV-1 strain. Overall, our studies highlight that VA1 replicates more slowly than HAstV-1 and elicits significantly different cellular responses, including the inability to disrupt cellular junctions and barrier permeability.

Influenza A virus (IAV) is a major pathogen of the human respiratory tract where the virus co-exists and interacts with bacterial populations comprising the respiratory microbiome. Synergies between IAV and respiratory bacterial pathogens promote enhanced inflammation and disease burden that exacerbate morbidity and mortality. We demonstrate that direct interactions between IAV and encapsulated bacteria commonly found in the respiratory tract promote environmental stability and infectivity of IAV. Antibiotic-mediated depletion of the respiratory bacterial flora abrogated IAV transmission in ferret models, indicating that these viral-bacterial interactions are operative for airborne transmission of IAV. Restoring IAV airborne transmission in antibiotic treated ferrets by co-infection with Streptococcus pneumoniae confirmed a role for specific members of the bacterial respiratory community in promoting IAV transmission. These results implicate a role for the bacterial respiratory flora in promoting airborne transmission of IAV.