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Structural divergence creates new functional features in alphavirus genomes.

Katrina M Kutchko1,2, Emily A Madden3, Clayton Morrison4

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Alphaviruses like Sindbis virus (SINV) and Venezuelan equine encephalitis virus (VEEV) have RNA structures crucial for their life cycle. These RNA structures are surprisingly not conserved between viruses, suggesting rapid evolution.

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Area of Science:

  • Virology
  • Molecular Biology
  • Genomics

Background:

  • Alphaviruses are mosquito-borne viruses causing significant human diseases.
  • Known RNA structural elements influence Sindbis virus (SINV) and Venezuelan equine encephalitis virus (VEEV) replication and pathogenesis.
  • A comprehensive genomic structural profile for these viruses is lacking.

Purpose of the Study:

  • To map and characterize RNA structural elements within the genomes of SINV and VEEV.
  • To identify novel functional RNA structures and assess their conservation between SINV and VEEV.

Main Methods:

  • Utilized the SHAPE-MaP (Selective 2′-Hydroxyl Acylation analyzed by Primer Extension and Mutational Profiling) technique.
  • Generated SHAPE-directed structural models for SINV and VEEV RNA genomes.
  • Compared identified RNA structures between the two alphaviruses.

Main Results:

  • SHAPE-MaP successfully identified known and novel RNA structural elements in SINV and VEEV genomes.
  • A newly identified functional RNA element in the SINV nsP1 region was found to be essential for infectivity.
  • The majority of identified RNA structures were not conserved between SINV and VEEV, despite similar genomic architecture.

Conclusions:

  • Alphavirus RNA genomes exhibit significant structural divergence despite sequence conservation.
  • RNA structural elements are critical for alphavirus biology and undergo rapid evolution.
  • Findings challenge traditional views on RNA structure conservation and suggest novel mechanisms for viral evolution and host immune system interaction.