Human Astroviruses: A Tale of Two Strains.

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.

Molecular evolutionary analysis of type-1 human astroviruses identifies putative sites under selection pressure on the capsid protein.

Human astroviruses (HAstV) are important enteric pathogens that can be classified into eight sero/genotypes (HAstV-1 to -8). Although the various HAstV types show global spread, type-1 strains tend to be predominant. Molecular analysis of the genomic region encoding the capsid protein (ORF2) has revealed discrete sequence variation, with different lineages within each HAstV type and at least three major lineages have been identified within HAstV-1. Longitudinal epidemiological surveillance has revealed temporal shift of the various HAstV-1 lineages. Metadata analysis of HAstV-1 sequences available in the databases also revealed temporal shifts of the circulation of HAstV-1 lineages, suggesting possible antigenic-related mechanisms of selection at the sub-genotype level. By comparison of HAstV-1 capsid sequences, lineage-defining residues under positive selection were identified. Structural analysis of HAstV-1 capsid allowed identifying at least six residues exposed on the virion surface. Two residues were located in the VP34 (shell region) whilst four residues were mapped in the VP25/27 (protruding region) of HAstV capsid protein, in proximity of the putative receptor binding S site. These findings suggest that mechanisms similar to those observed and/or hypothesized for other enteric viruses are also shaping the evolution of HAstVs, with intra-typic diversification being a possible mechanism to decrease the antigenic pressure to which these viruses are exposed.

Epidemiology and genetic diversity of human astrovirus infection among hospitalized patients with acute diarrhea in Bangladesh from 2010 to 2012.

BACKGROUND: Globally, human astroviruses (HAstVs) have emerged as another common cause of non-bacterial acute gastroenteritis. Limited data exist on the epidemiology and genetic diversity of HAstVs in Bangladesh. OBJECTIVE: We describe the epidemiology of HAstV-associated diarrhea among hospitalized patients, including HAstV genotypes, clinical symptoms and co-infecting pathogens. STUDY DESIGN: Stool samples were collected from an ongoing diarrhea etiology surveillance during 2010-2012. HAstV was detected using RT-PCR and positive samples were subsequently tested for other common viral and bacterial pathogens. Phylogenetic analysis was performed and genotyped HAstV sequences were compared with previously reported Bangladeshi HAstV strains. RESULTS: Of 826 fecal specimens, HAstV was detected in 26 cases (3.1%) and the majority of these cases (92%) was observed in children under 3 years of age. For 6 out of the 26 cases (23%) no other co-infecting pathogens were observed, whereas for the 20 remaining cases (77%) a variety of other known enteric viral and bacterial pathogens were observed. Based on the overlap region between ORF1b (RdRp) and ORF2 (capsid), five different genotypes (HAstV-1, -2, -3, -5 and -6) were identified circulating during the study period, with HAstV-1 being the predominant type. Genetic analysis revealed that HAstV-1 strains detected in this study were distantly related (<90% similarity of the capsid protein on the nt level) with HAstV-1 strains previously reported from Bangladesh. CONCLUSION: Our study provides an epidemiological overview and genetic diversity of HAstVs associated with acute diarrhea in Bangladesh.