The Induction of Infectivity in Human Astrovirus in Response to Capsid Proteolysis

Date
2013-06-28
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Abstract

Astrovirus is a non-enveloped, T=3, positive-sense RNA virus that presents with self-limiting gastroenteritis; however, it has been additionally associated with serious presentations such as nephritis, hepatitis, and encephalitis, which is compounded by its propensity to engage in cross-species penetrations. Astrovirus undergoes a complex capsid maturation process mediated by host proteases in which an inert, immature capsid composed of VP90 is sequentially cleaved to yield a highly infectious particle composed of VP34 and VP27/VP25, which form the capsid shell and spikes, respectively. By overexpressing a VP9070-418 truncate in insect cells, we have demonstrated that the shell domain alone cannot support particle assembly, implying a crucial role for the dimeric contacts within the spike. Various monomeric, shell domain truncates (i.e. VP9071-252, VP9071-283, VP9071-313, and VP9071-415) have been successfully expressed and purified, but none yielded useful crystals, suggesting the structural context of the capsid lattice may be needed to stabilize their conformational flexibility.

Description
Degree
Master of Arts
Type
Thesis
Keywords
X-ray crystallography, Virology, Astrovirus, Infectivity, Structure, Assembly, Biophysics, Biochemistry, HAstV, Capsid, RNA virus
Citation

Harper, Justin. "The Induction of Infectivity in Human Astrovirus in Response to Capsid Proteolysis." (2013) Master’s Thesis, Rice University. https://hdl.handle.net/1911/77163.

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