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Updated: Jul 19, 2025

Arbovirus Infections As Screening Tools for the Identification of Viral Immunomodulators and Host Antiviral Factors
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Arbovirus Infections As Screening Tools for the Identification of Viral Immunomodulators and Host Antiviral Factors

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The phenuivirus Toscana virus makes an atypical use of vacuolar acidity to enter host cells

Jana Koch1,2,3, Qilin Xin3, Martin Obr4

  • 1Center for Integrative Infectious Diseases Research (CIID), University Hospital Heidelberg, Heidelberg, Germany.

Plos Pathogens
|August 14, 2023
PubMed

Insights

Toscana virus enters human cells through endocytosis, utilizing late endosomes and vacuolar acidity for entry. This study reveals an atypical mechanism for this common Mediterranean arbovirus.

Area of Science:

  • Virology
  • Cell Biology
  • Infectious Diseases

Background:

  • Toscana virus causes significant arboviral disease in the Mediterranean.
  • Early virus-host interactions and entry mechanisms are not well understood.

Purpose of the Study:

  • To investigate the early interactions and entry mechanisms of Toscana virus into human host cells.
  • To characterize the role of endosomal compartments and pH in Toscana virus entry.

Main Methods:

  • Utilized induced pluripotent stem cell (iPSC)-derived human neurons and cell lines.
  • Tracked virus binding, endocytosis, and trafficking through endosomal compartments (Rab5a+, Rab7a+, LAMP-1+).
  • Assessed the impact of vacuolar pH on viral fusion and infectivity.

Main Results:

  • Toscana virus binds specifically to host cells and undergoes endocytosis within 10 minutes.
  • Virions traffic through early and late endosomes, with penetration occurring within 30 minutes.
  • Entry depends on vacuolar acidification, with optimal fusion at pH 5.5, and demonstrates atypical pH tolerance.

Conclusions:

  • Toscana virus is a late-penetrating virus.
  • The virus exhibits an unusual reliance on vacuolar acidity for host cell entry.
  • Understanding these mechanisms is crucial for combating Toscana virus infections.

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