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Conformational changes required for reovirus cell entry are sensitive to pH.

Deepti Thete1, Pranav Danthi1

  • 1Department of Biology, Indiana University, Bloomington, IN 47405, United States.

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Reovirus cell entry depends on pH-driven conversion of viral particles. Lowering endosomal pH with Ouabain blocked infection by hindering this critical viral transformation step.

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Area of Science:

  • Virology
  • Cell Biology
  • Biochemistry

Background:

  • Reovirus cell entry involves particle disassembly into infectious subvirion particles (ISVPs).
  • ISVPs must convert to ISVP(*) for membrane penetration.
  • This conversion occurs at low pH in endosomes or neutral pH extracellularly.

Purpose of the Study:

  • To investigate if distinct pH environments influence reovirus cell entry efficiency.
  • To determine the effect of experimentally lowered endosomal pH on reovirus infection.

Main Methods:

  • Utilized Ouabain to reduce endosomal pH in host cells.
  • Assessed reovirus attachment, internalization, ISVP formation, and ISVP(*) formation.
  • Performed in vitro ISVP-to-ISVP(*) conversion assays at varying pH.

Main Results:

  • Ouabain treatment completely blocked reovirus infection.
  • Virus attachment, internalization, and ISVP formation remained unaffected by Ouabain.
  • The efficiency of ISVP(*) formation was significantly diminished in Ouabain-treated cells.
  • Low pH in vitro reduced the efficiency of ISVP-to-ISVP(*) conversion.

Conclusions:

  • The pH of the compartment where ISVP-to-ISVP(*) conversion occurs is critical for reovirus cell entry efficiency.
  • Experimentally lowering endosomal pH impairs reovirus infection by inhibiting viral particle conversion.