TY - JOUR
T1 - Immature and mature human astrovirus
T2 - Structure, conformational changes, and similarities to hepatitis e virus
AU - Dryden, Kelly A.
AU - Tihova, Mariana
AU - Nowotny, Norbert
AU - Matsui, Suzanne M.
AU - Mendez, Ernesto
AU - Yeager, Mark
N1 - Funding Information:
We gratefully acknowledge Dr. Yizhi Tao for providing her model of astrovirus VP25. We also thank Dr. Barbie Ganser-Pornillos for helpful discussions and Yunuen Acevedo for technical support. Molecular graphics images were produced using the UCSF Chimera package from the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco [supported by National Institutes of Health (NIH) P41 RR001081 ]. This work was supported by funding from the Austrian Science Fund ( J1348 ) to N.N., DGAPA-UNAM ( 219910 ) and CONACyT ( 79574 ) to E.M., NIH R21 AI43513 to S.M.M., and NIH R01 GM066087 to M.Y.
PY - 2012/10/5
Y1 - 2012/10/5
N2 - Human astroviruses (HAstVs) are a major cause of gastroenteritis. HAstV assembles from the structural protein VP90 and undergoes a cascade of proteolytic cleavages. Cleavage to VP70 is required for release of immature particles from cells, and subsequent cleavage by trypsin confers infectivity. We used electron cryomicroscopy and icosahedral image analysis to determine the first experimentally derived, three-dimensional structures of an immature VP70 virion and a fully proteolyzed, infectious virion. Both particles display T = 3 icosahedral symmetry and nearly identical solid capsid shells with diameters of ∼ 350 Å. Globular spikes emanate from the capsid surface, yielding an overall diameter of ∼ 440 Å. While the immature particles display 90 dimeric spikes, the mature capsid only displays 30 spikes, located on the icosahedral 2-fold axes. Loss of the 60 peripentonal spikes likely plays an important role in viral infectivity. In addition, immature HAstV bears a striking resemblance to the structure of hepatitis E virus (HEV)-like particles, as previously predicted from structural similarity of the crystal structure of the astrovirus spike domain with the HEV P-domain [Dong, J., Dong, L., Méndez, E. & Tao, Y. (2011). Crystal structure of the human astrovirus capsid spike. Proc. Natl. Acad. Sci. USA 108, 12681-12686]. Similarities between their capsid shells and dimeric spikes and between the sequences of their capsid proteins suggest that these viral families are phylogenetically related and may share common assembly and activation mechanisms.
AB - Human astroviruses (HAstVs) are a major cause of gastroenteritis. HAstV assembles from the structural protein VP90 and undergoes a cascade of proteolytic cleavages. Cleavage to VP70 is required for release of immature particles from cells, and subsequent cleavage by trypsin confers infectivity. We used electron cryomicroscopy and icosahedral image analysis to determine the first experimentally derived, three-dimensional structures of an immature VP70 virion and a fully proteolyzed, infectious virion. Both particles display T = 3 icosahedral symmetry and nearly identical solid capsid shells with diameters of ∼ 350 Å. Globular spikes emanate from the capsid surface, yielding an overall diameter of ∼ 440 Å. While the immature particles display 90 dimeric spikes, the mature capsid only displays 30 spikes, located on the icosahedral 2-fold axes. Loss of the 60 peripentonal spikes likely plays an important role in viral infectivity. In addition, immature HAstV bears a striking resemblance to the structure of hepatitis E virus (HEV)-like particles, as previously predicted from structural similarity of the crystal structure of the astrovirus spike domain with the HEV P-domain [Dong, J., Dong, L., Méndez, E. & Tao, Y. (2011). Crystal structure of the human astrovirus capsid spike. Proc. Natl. Acad. Sci. USA 108, 12681-12686]. Similarities between their capsid shells and dimeric spikes and between the sequences of their capsid proteins suggest that these viral families are phylogenetically related and may share common assembly and activation mechanisms.
KW - cryomicroscopy
KW - electron microscopy
KW - image analysis
KW - virus structure
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U2 - 10.1016/j.jmb.2012.06.029
DO - 10.1016/j.jmb.2012.06.029
M3 - Article
C2 - 22743104
AN - SCOPUS:84865685562
SN - 0022-2836
VL - 422
SP - 650
EP - 658
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 5
ER -