Cryo-EM Reveals Architectural Diversity in Active Rotavirus Particles

Mary Hauser, William Dearnaley, Cameron Varano, Michael Casasanta, Sarah M. McDonald, Deb Kelly

Research output: Contribution to journalArticle

Abstract

Rotavirus is a well-studied RNA virus that causes severe gastroenteritis in children. During viral entry, the outer layer of the virion is shed, creating a double-layered particle (DLP) that is competent to perform viral transcription (i.e., mRNA synthesis) and launch infection. While inactive forms of rotavirus DLPs have been structurally characterized in detail, information about the transcriptionally-active DLP remains limited. Here, we used cryo-Electron Microscopy (cryo-EM) and 3D image reconstructions to compare the structures of internal protein components in transcriptionally-active versus inactive DLPs. Our findings showed that transcriptionally-active DLPs gained internal order as mRNA synthesis unfolded, while inactive DLPs remained dynamically disordered. Regions of viral protein/RNA constituents were analyzed across two different axes of symmetry to provide a more comprehensive view of moving components. Taken together, our results bring forth a new view of active DLPs, which may enable future pharmacological strategies aimed at obliterating rotavirus transcription as a therapeutic approach.

Original languageEnglish (US)
Pages (from-to)1178-1183
Number of pages6
JournalComputational and Structural Biotechnology Journal
Volume17
DOIs
StatePublished - Jan 1 2019

Fingerprint

Rotavirus
Transcription
RNA
Proteins
Messenger RNA
Viral Proteins
Image reconstruction
Viruses
Electron microscopy
Cryoelectron Microscopy
Computer-Assisted Image Processing
RNA Viruses
Viral RNA
Gastroenteritis
Virion
Pharmacology
Infection
Therapeutics

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biophysics
  • Structural Biology
  • Biochemistry
  • Genetics
  • Computer Science Applications

Cite this

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Cryo-EM Reveals Architectural Diversity in Active Rotavirus Particles. / Hauser, Mary; Dearnaley, William; Varano, Cameron; Casasanta, Michael; McDonald, Sarah M.; Kelly, Deb.

In: Computational and Structural Biotechnology Journal, Vol. 17, 01.01.2019, p. 1178-1183.

Research output: Contribution to journalArticle

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