---
_id: '14255'
abstract:
- lang: eng
  text: Toscana virus is a major cause of arboviral disease in humans in the Mediterranean
    basin during summer. However, early virus-host cell interactions and entry mechanisms
    remain poorly characterized. Investigating iPSC-derived human neurons and cell
    lines, we found that virus binding to the cell surface was specific, and 50% of
    bound virions were endocytosed within 10 min. Virions entered Rab5a+ early endosomes
    and, subsequently, Rab7a+ and LAMP-1+ late endosomal compartments. Penetration
    required intact late endosomes and occurred within 30 min following internalization.
    Virus entry relied on vacuolar acidification, with an optimal pH for viral membrane
    fusion at pH 5.5. The pH threshold increased to 5.8 with longer pre-exposure of
    virions to the slightly acidic pH in early endosomes. Strikingly, the particles
    remained infectious after entering late endosomes with a pH below the fusion threshold.
    Overall, our study establishes Toscana virus as a late-penetrating virus and reveals
    an atypical use of vacuolar acidity by this virus to enter host cells.
acknowledged_ssus:
- _id: EM-Fac
acknowledgement: "We acknowledge Elodie Chatre and the Imaging Platform Platim, SFR
  Biosciences, Lyon, as well as Vibor Laketa and the Infectious Diseases Imaging Platform
  (IDIP) at the Center for Integrative Infectious Disease Research (CIID) Heidelberg.
  The sand fly cell lines were supplied by the Tick Cell Biobank at the University
  of Liverpool. F.K.M.S. acknowledges support from the Scientific Service Units (SSUs)
  of ISTA through resources provided by the Electron Microscopy Facility (EMF).\r\nThis
  work was supported by CellNetworks Research Group funds and Deutsche Forschungsgemeinschaft
  (DFG) funding (LO-2338/3-1) and the Agence Nationale de la Recherche (ANR) funding
  (grant numbers ANR-21-CE11-0012 and ANR-22-CE15-0034), all awarded to P.-Y.L. This
  work was also supported by the LABEX ECOFECT (ANR-11-LABX-0048) of Université de
  Lyon (UDL), within the program “Investissements d’Avenir” (ANR-11-IDEX-0007) operated
  by the ANR and by the RESPOND program of the UDL (awarded to P.-Y.L) . C.A. was
  supported by the Chica and Heinz Schaller Research Group funds, NARSAD 2019 award,
  a Fritz Thyssen Research Grant, and the SFB1158-S02 grant. L.B-S. is supported by
  a United Kingdom Biotechnology and Biological Sciences Research Council grant (BB/P024270/1)
  and a Wellcome Trust grant (223743/Z/21/Z). F.K.M.S acknowledges support from the
  Austrian Science Fund (FWF, P31445). J.K. received a salary from the DFG (LO-2338/3-1)
  and then from the ANR (ANR-11-LABX-0048). The salary of Z.M.U. was partially covered
  by the DFG (LO-2338/3-1). S.K. received a salary from the DFG (SFB1129). We are
  grateful to the Chinese Scholarship Council (CSC; 201904910701), DAAD/ANID (57451854/62180003),
  the Rufus A. Kellogg fellowship program (Amherst College, Massachusetts, USA) for
  awarding fellowships to Q.X., J.C., and H.A.A., respectively."
article_number: e1011562
article_processing_charge: Yes
article_type: original
author:
- first_name: Jana
  full_name: Koch, Jana
  last_name: Koch
- first_name: Qilin
  full_name: Xin, Qilin
  last_name: Xin
- first_name: Martin
  full_name: Obr, Martin
  id: 4741CA5A-F248-11E8-B48F-1D18A9856A87
  last_name: Obr
  orcid: 0000-0003-1756-6564
- first_name: Alicia
  full_name: Schäfer, Alicia
  last_name: Schäfer
- first_name: Nina
  full_name: Rolfs, Nina
  last_name: Rolfs
- first_name: Holda A.
  full_name: Anagho, Holda A.
  last_name: Anagho
- first_name: Aiste
  full_name: Kudulyte, Aiste
  last_name: Kudulyte
- first_name: Lea
  full_name: Woltereck, Lea
  last_name: Woltereck
- first_name: Susann
  full_name: Kummer, Susann
  last_name: Kummer
- first_name: Joaquin
  full_name: Campos, Joaquin
  last_name: Campos
- first_name: Zina M.
  full_name: Uckeley, Zina M.
  last_name: Uckeley
- first_name: Lesley
  full_name: Bell-Sakyi, Lesley
  last_name: Bell-Sakyi
- first_name: Hans Georg
  full_name: Kräusslich, Hans Georg
  last_name: Kräusslich
- first_name: Florian Km
  full_name: Schur, Florian Km
  id: 48AD8942-F248-11E8-B48F-1D18A9856A87
  last_name: Schur
  orcid: 0000-0003-4790-8078
- first_name: Claudio
  full_name: Acuna, Claudio
  last_name: Acuna
- first_name: Pierre Yves
  full_name: Lozach, Pierre Yves
  last_name: Lozach
citation:
  ama: Koch J, Xin Q, Obr M, et al. The phenuivirus Toscana virus makes an atypical
    use of vacuolar acidity to enter host cells. <i>PLoS Pathogens</i>. 2023;19(8).
    doi:<a href="https://doi.org/10.1371/journal.ppat.1011562">10.1371/journal.ppat.1011562</a>
  apa: Koch, J., Xin, Q., Obr, M., Schäfer, A., Rolfs, N., Anagho, H. A., … Lozach,
    P. Y. (2023). The phenuivirus Toscana virus makes an atypical use of vacuolar
    acidity to enter host cells. <i>PLoS Pathogens</i>. Public Library of Science.
    <a href="https://doi.org/10.1371/journal.ppat.1011562">https://doi.org/10.1371/journal.ppat.1011562</a>
  chicago: Koch, Jana, Qilin Xin, Martin Obr, Alicia Schäfer, Nina Rolfs, Holda A.
    Anagho, Aiste Kudulyte, et al. “The Phenuivirus Toscana Virus Makes an Atypical
    Use of Vacuolar Acidity to Enter Host Cells.” <i>PLoS Pathogens</i>. Public Library
    of Science, 2023. <a href="https://doi.org/10.1371/journal.ppat.1011562">https://doi.org/10.1371/journal.ppat.1011562</a>.
  ieee: J. Koch <i>et al.</i>, “The phenuivirus Toscana virus makes an atypical use
    of vacuolar acidity to enter host cells,” <i>PLoS Pathogens</i>, vol. 19, no.
    8. Public Library of Science, 2023.
  ista: Koch J, Xin Q, Obr M, Schäfer A, Rolfs N, Anagho HA, Kudulyte A, Woltereck
    L, Kummer S, Campos J, Uckeley ZM, Bell-Sakyi L, Kräusslich HG, Schur FK, Acuna
    C, Lozach PY. 2023. The phenuivirus Toscana virus makes an atypical use of vacuolar
    acidity to enter host cells. PLoS Pathogens. 19(8), e1011562.
  mla: Koch, Jana, et al. “The Phenuivirus Toscana Virus Makes an Atypical Use of
    Vacuolar Acidity to Enter Host Cells.” <i>PLoS Pathogens</i>, vol. 19, no. 8,
    e1011562, Public Library of Science, 2023, doi:<a href="https://doi.org/10.1371/journal.ppat.1011562">10.1371/journal.ppat.1011562</a>.
  short: J. Koch, Q. Xin, M. Obr, A. Schäfer, N. Rolfs, H.A. Anagho, A. Kudulyte,
    L. Woltereck, S. Kummer, J. Campos, Z.M. Uckeley, L. Bell-Sakyi, H.G. Kräusslich,
    F.K. Schur, C. Acuna, P.Y. Lozach, PLoS Pathogens 19 (2023).
date_created: 2023-09-03T22:01:14Z
date_published: 2023-08-14T00:00:00Z
date_updated: 2025-04-15T08:24:50Z
day: '14'
ddc:
- '570'
department:
- _id: FlSc
doi: 10.1371/journal.ppat.1011562
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  call_identifier: FWF
  grant_number: P31445
  name: Structural conservation and diversity in retroviral capsid
publication: PLoS Pathogens
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  issn:
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publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
scopus_import: '1'
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title: The phenuivirus Toscana virus makes an atypical use of vacuolar acidity to
  enter host cells
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...
---
_id: '9046'
acknowledgement: Our work was supported by the Swedish Research Council (grant 2017-01527)
  to DIA
article_number: e1009172
article_processing_charge: No
article_type: original
author:
- first_name: Roderich
  full_name: Römhild, Roderich
  id: 68E56E44-62B0-11EA-B963-444F3DDC885E
  last_name: Römhild
  orcid: 0000-0001-9480-5261
- first_name: Dan I.
  full_name: Andersson, Dan I.
  last_name: Andersson
citation:
  ama: Römhild R, Andersson DI. Mechanisms and therapeutic potential of collateral
    sensitivity to antibiotics. <i>PLoS Pathogens</i>. 2021;17(1). doi:<a href="https://doi.org/10.1371/journal.ppat.1009172">10.1371/journal.ppat.1009172</a>
  apa: Römhild, R., &#38; Andersson, D. I. (2021). Mechanisms and therapeutic potential
    of collateral sensitivity to antibiotics. <i>PLoS Pathogens</i>. Public Library
    of Science. <a href="https://doi.org/10.1371/journal.ppat.1009172">https://doi.org/10.1371/journal.ppat.1009172</a>
  chicago: Römhild, Roderich, and Dan I. Andersson. “Mechanisms and Therapeutic Potential
    of Collateral Sensitivity to Antibiotics.” <i>PLoS Pathogens</i>. Public Library
    of Science, 2021. <a href="https://doi.org/10.1371/journal.ppat.1009172">https://doi.org/10.1371/journal.ppat.1009172</a>.
  ieee: R. Römhild and D. I. Andersson, “Mechanisms and therapeutic potential of collateral
    sensitivity to antibiotics,” <i>PLoS Pathogens</i>, vol. 17, no. 1. Public Library
    of Science, 2021.
  ista: Römhild R, Andersson DI. 2021. Mechanisms and therapeutic potential of collateral
    sensitivity to antibiotics. PLoS Pathogens. 17(1), e1009172.
  mla: Römhild, Roderich, and Dan I. Andersson. “Mechanisms and Therapeutic Potential
    of Collateral Sensitivity to Antibiotics.” <i>PLoS Pathogens</i>, vol. 17, no.
    1, e1009172, Public Library of Science, 2021, doi:<a href="https://doi.org/10.1371/journal.ppat.1009172">10.1371/journal.ppat.1009172</a>.
  short: R. Römhild, D.I. Andersson, PLoS Pathogens 17 (2021).
date_created: 2021-01-31T23:01:21Z
date_published: 2021-01-14T00:00:00Z
date_updated: 2025-07-10T12:01:33Z
day: '14'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.1371/journal.ppat.1009172
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  pmid:
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  file_name: 2021_PlosPathogens_Roemhild.pdf
  file_size: 570066
  relation: main_file
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issue: '1'
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month: '01'
oa: 1
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publication: PLoS Pathogens
publication_identifier:
  eissn:
  - 1553-7374
  issn:
  - 1553-7366
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
scopus_import: '1'
status: public
title: Mechanisms and therapeutic potential of collateral sensitivity to antibiotics
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
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  short: CC BY (4.0)
type: journal_article
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...