Structure and antigenicity of the divergent human astrovirus VA1 capsid spike.

Human astrovirus (HAstV) is a known cause of viral gastroenteritis in children worldwide, but HAstV can cause also severe and systemic infections in immunocompromised patients. There are three clades of HAstV: classical, MLB, and VA/HMO. While all three clades are found in gastrointestinal samples, HAstV-VA/HMO is the main clade associated with meningitis and encephalitis in immunocompromised patients. To understand how the HAstV-VA/HMO can infect the central nervous system, we investigated its sequence-divergent capsid spike, which functions in cell attachment and may influence viral tropism. Here we report the high-resolution crystal structures of the HAstV-VA1 capsid spike from strains isolated from patients with gastrointestinal and neuronal disease. The HAstV-VA1 spike forms a dimer and shares a core beta-barrel structure with other astrovirus capsid spikes but is otherwise strikingly different, suggesting that HAstV-VA1 may utilize a different cell receptor, and an infection competition assay supports this hypothesis. Furthermore, by mapping the capsid protease cleavage site onto the structure, the maturation and assembly of the HAstV-VA1 capsid is revealed. Finally, comparison of gastrointestinal and neuronal HAstV-VA1 sequences, structures, and antigenicity suggests that neuronal HAstV-VA1 strains may have acquired immune escape mutations. Overall, our studies on the HAstV-VA1 capsid spike lay a foundation to further investigate the biology of HAstV-VA/HMO and to develop vaccines and therapeutics targeting it.

Structure of the divergent human astrovirus MLB capsid spike.

Despite their worldwide prevalence and association with human disease, the molecular bases of human astrovirus (HAstV) infection and evolution remain poorly characterized. Here, we report the structure of the capsid protein spike of the divergent HAstV MLB clade (HAstV MLB). While the structure shares a similar folding topology with that of classical-clade HAstV spikes, it is otherwise strikingly different. We find no evidence of a conserved receptor-binding site between the MLB and classical HAstV spikes, suggesting that MLB and classical HAstVs utilize different receptors for host-cell attachment. We provide evidence for this hypothesis using a novel HAstV infection competition assay. Comparisons of the HAstV MLB spike structure with structures predicted from its sequence reveal poor matches, but template-based predictions were surprisingly accurate relative to machine-learning-based predictions. Our data provide a foundation for understanding the mechanisms of infection by diverse HAstVs and can support structure determination in similarly unstudied systems.

Human Astrovirus 1-8 Seroprevalence Evaluation in a United States Adult Population.

Human astroviruses are an important cause of viral gastroenteritis globally, yet few studies have investigated the serostatus of adults to establish rates of previous infection. Here, we applied biolayer interferometry immunosorbent assay (BLI-ISA), a recently developed serosurveillance technique, to measure the presence of blood plasma IgG antibodies directed towards the human astrovirus capsid spikes from serotypes 1-8 in a cross-sectional sample of a United States adult population. The seroprevalence rates of IgG antibodies were 73% for human astrovirus serotype 1, 62% for serotype 3, 52% for serotype 4, 29% for serotype 5, 27% for serotype 8, 22% for serotype 2, 8% for serotype 6, and 8% for serotype 7. Notably, seroprevalence rates for capsid spike antigens correlate with neutralizing antibody rates determined previously. This work is the first seroprevalence study evaluating all eight classical human astrovirus serotypes.

Exchange Capability of Cationic Silver 4,4'-Bipyrdine Materials for Potential Water Remediation: Structure, Stability, and Anion Exchange Properties.

An in-depth study of the class of cationic materials [Ag(4,4'-bipy)+][X-] (where X- = CH3CO2-, NO3-, BF4-, ClO4-, and MnO4-) has led to key insights on the relationship between anion hydration energy, material structure, solubility, and stability. Since these materials show promise for their potential as water remediation tools, understanding their properties in detail is of significant importance. The structure of the starting and ending materials is the main driving force behind the resultant stability and solubility and can be successfully used to predict the ion exchange capabilities. The solubility trend was determined to be, from most soluble to least soluble, X- = CH3CO2- > NO3- ∼ BF4- > ClO4- > MnO4-. Kinetics and thermal stability also follow predictable trends but involve additional factors. For instance, the kinetics of NO3- to MnO4- exchange was much slower than expected based on that seen for NO3- to ClO4-. Powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FTIR) were used to characterize the materials. Solubility was determined by inductively coupled plasma optical emission spectroscopy (ICP-OES) analysis. Ion exchange was analyzed with ion chromatography (IC) and ultraviolet-visible spectroscopy (UV-vis), and thermal stability was determined with thermogravimetric analysis (TGA).