Human Astroviruses: A Tale of Two Strains

Abstract

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.

Astrovirus-induced epithelial-mesenchymal transition via activated TGF-β increases viral replication

“…Unlike classical HAstVs, HAstV-VA1 has rarely been linked to diarrhea [ 43 , 44 ] but has been reported in association with neurological disease [ 31 , 45 ]. Classical and non-classical HAstVs are genetically distinct and differ on key factors of replication and pathogenesis [ 46 , 47 ]. Since the novel HAstV strain was discovered just over 10 years ago, investigations into its pathogenesis are just beginning and our finding that it does not induce EMT may reveal an underlying fundamental difference between it and classical HAstVs.…”

High Seropositivity Rate of Neutralizing Antibodies to Astrovirus VA1 in Human Populations

“…The observation that commercially available IVIG lots contain neutralizing antibodies to VA1 suggests that IVIG could be used for passive immunization of patients at risk for infection and as a treatment for acute infections with VA1. Interferon, nitazoxanide, ribavirin, and favipiravir have been previously identified to have antiviral activity against VA1 in cell culture ( 34 , 38 , 39 ), but it is unclear if these therapies are effective in vivo .…”

Neonatal Fc receptor is a functional receptor for human astrovirus

“…FcRn is bound to the spike protein (VP27) of HAstVs (Fig. 5D); however, the amino acid sequences of the spike regions of HAstV1 and VA1 are quite different 20 and, therefore, VA1 and MLB could not use FcRn as a receptor. Indeed, while VA1 infected primary astrocytes and immortalized neuronal cell lines, a slight HAstV4 infection was observed 31 .…”