The group of Dr. Rebecca DuBois and colleagues have determined the crystal structure of the divergent human astrovirus VA1 capsid spike domain. Initially recognized as a primary cause of viral diarrhea, human astroviruses have more recently garnered attention for their association with viral encephalitis in immunocompromised individuals, particularly the sequence-divergent VA1 strains. This research unveils the high-resolution capsid spike structures from gastrointestinal and neurological human astrovirus VA1 strains. Compared to the canonical human astrovirus capsid spike structure, the VA1 capsid spike structure displays significant variations in size, shape, and surface characteristics, suggesting that human astrovirus VA1 may utilize a mechanism to attach to human cells compared to canonical human astroviruses. Furthermore, this research identified and mapped protease cleavage sites on the capsid needed for virus maturation. Finally, antibody binding assays reveal that neurological VA1 strains may have evolved mutations to evade immunoglobulin therapy. This research provides a structural basis for investigating the infection mechanisms of human astrovirus VA1 strains and advancing tailored approaches for diagnostics, vaccines, and therapeutics.
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Figure: The crystal structure of the human astrovirus VA1 capsid spike dimer presented as a cartoon model, with one protomer colored rainbow from the N-terminus (blue) to the C-terminus (red), and the other protomer colored grey. Image credit: Dr. Anisa Ghosh . |
Citation: Ghosh, A, Delgado-Cunningham, K, Lopez, T, Green, K, Arias, CF, DuBois, RM, "Structure and antigenicity of the divergent human astrovirus VA1 capsid spike," PLoS Patho. 20 (2), e1012028 (2024). DOI: 10.1371/journal.ppat.1012028
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