---
_id: '10639'
abstract:
- lang: eng
text: With more than 80 members worldwide, the Orthobunyavirus genus in the Peribunyaviridae
family is a large genus of enveloped RNA viruses, many of which are emerging pathogens
in humans and livestock. How orthobunyaviruses (OBVs) penetrate and infect mammalian
host cells remains poorly characterized. Here, we investigated the entry mechanisms
of the OBV Germiston (GERV). Viral particles were visualized by cryo-electron
microscopy and appeared roughly spherical with an average diameter of 98 nm. Labeling
of the virus with fluorescent dyes did not adversely affect its infectivity and
allowed the monitoring of single particles in fixed and live cells. Using this
approach, we found that endocytic internalization of bound viruses was asynchronous
and occurred within 30-40 min. The virus entered Rab5a+ early endosomes and, subsequently,
late endosomal vacuoles containing Rab7a but not LAMP-1. Infectious entry did
not require proteolytic cleavage, and endosomal acidification was sufficient and
necessary for viral fusion. Acid-activated penetration began 15-25 min after initiation
of virus internalization and relied on maturation of early endosomes to late endosomes.
The optimal pH for viral membrane fusion was slightly below 6.0, and penetration
was hampered when the potassium influx was abolished. Overall, our study provides
real-time visualization of GERV entry into host cells and demonstrates the importance
of late endosomal maturation in facilitating OBV penetration.
acknowledged_ssus:
- _id: EM-Fac
acknowledgement: This work was supported by INRAE starter funds, Project IDEXLYON (University of Lyon)
within the Programme Investissements d’Avenir (ANR-16-IDEX-0005), and FINOVIAO14
(Fondation pour l’Université de Lyon), all to P.Y.L. This work was also supported by
CellNetworks Research Group funds and Deutsche Forschungsgemeinschaft (DFG) funding
(grant numbers LO-2338/1-1 and LO-2338/3-1) awarded to P.Y.L., Austrian Science Fund
(FWF) grant P31445 to F.K.M.S., a Chinese Scholarship Council (CSC;no. 201904910701)
fellowship to Q.X., and a ministére de l’enseignement supérieur, de la recherche et de
l’innovation (MESRI) doctoral thesis grant to M.D.
article_number: e02146-21
article_processing_charge: No
article_type: original
author:
- first_name: Stefan
full_name: Windhaber, Stefan
last_name: Windhaber
- first_name: Qilin
full_name: Xin, Qilin
last_name: Xin
- first_name: Zina M.
full_name: Uckeley, Zina M.
last_name: Uckeley
- first_name: Jana
full_name: Koch, Jana
last_name: Koch
- first_name: Martin
full_name: Obr, Martin
id: 4741CA5A-F248-11E8-B48F-1D18A9856A87
last_name: Obr
- first_name: Céline
full_name: Garnier, Céline
last_name: Garnier
- first_name: Catherine
full_name: Luengo-Guyonnot, Catherine
last_name: Luengo-Guyonnot
- first_name: Maëva
full_name: Duboeuf, Maëva
last_name: Duboeuf
- 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: Pierre-Yves
full_name: Lozach, Pierre-Yves
last_name: Lozach
citation:
ama: Windhaber S, Xin Q, Uckeley ZM, et al. The Orthobunyavirus Germiston enters
host cells from late endosomes. Journal of Virology. 2022;96(5). doi:10.1128/jvi.02146-21
apa: Windhaber, S., Xin, Q., Uckeley, Z. M., Koch, J., Obr, M., Garnier, C., … Lozach,
P.-Y. (2022). The Orthobunyavirus Germiston enters host cells from late endosomes.
Journal of Virology. American Society for Microbiology. https://doi.org/10.1128/jvi.02146-21
chicago: Windhaber, Stefan, Qilin Xin, Zina M. Uckeley, Jana Koch, Martin Obr, Céline
Garnier, Catherine Luengo-Guyonnot, Maëva Duboeuf, Florian KM Schur, and Pierre-Yves
Lozach. “The Orthobunyavirus Germiston Enters Host Cells from Late Endosomes.”
Journal of Virology. American Society for Microbiology, 2022. https://doi.org/10.1128/jvi.02146-21.
ieee: S. Windhaber et al., “The Orthobunyavirus Germiston enters host cells
from late endosomes,” Journal of Virology, vol. 96, no. 5. American Society
for Microbiology, 2022.
ista: Windhaber S, Xin Q, Uckeley ZM, Koch J, Obr M, Garnier C, Luengo-Guyonnot
C, Duboeuf M, Schur FK, Lozach P-Y. 2022. The Orthobunyavirus Germiston enters
host cells from late endosomes. Journal of Virology. 96(5), e02146-21.
mla: Windhaber, Stefan, et al. “The Orthobunyavirus Germiston Enters Host Cells
from Late Endosomes.” Journal of Virology, vol. 96, no. 5, e02146-21, American
Society for Microbiology, 2022, doi:10.1128/jvi.02146-21.
short: S. Windhaber, Q. Xin, Z.M. Uckeley, J. Koch, M. Obr, C. Garnier, C. Luengo-Guyonnot,
M. Duboeuf, F.K. Schur, P.-Y. Lozach, Journal of Virology 96 (2022).
date_created: 2022-01-18T10:04:18Z
date_published: 2022-03-01T00:00:00Z
date_updated: 2023-08-02T13:52:33Z
day: '01'
department:
- _id: FlSc
doi: 10.1128/jvi.02146-21
external_id:
isi:
- '000779305000033'
pmid:
- '35019710'
intvolume: ' 96'
isi: 1
issue: '5'
keyword:
- virology
- insect science
- immunology
- microbiology
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906410
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 26736D6A-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P31445
name: Structural conservation and diversity in retroviral capsid
publication: Journal of Virology
publication_identifier:
eissn:
- 1098-5514
issn:
- 0022-538X
publication_status: published
publisher: American Society for Microbiology
quality_controlled: '1'
scopus_import: '1'
status: public
title: The Orthobunyavirus Germiston enters host cells from late endosomes
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 96
year: '2022'
...
---
_id: '10103'
abstract:
- lang: eng
text: The small cellular molecule inositol hexakisphosphate (IP6) has been known
for ~20 years to promote the in vitro assembly of HIV-1 into immature virus-like
particles. However, the molecular details underlying this effect have been determined
only recently, with the identification of the IP6 binding site in the immature
Gag lattice. IP6 also promotes formation of the mature capsid protein (CA) lattice
via a second IP6 binding site, and enhances core stability, creating a favorable
environment for reverse transcription. IP6 also enhances assembly of other retroviruses,
from both the Lentivirus and the Alpharetrovirus genera. These findings suggest
that IP6 may have a conserved function throughout the family Retroviridae. Here,
we discuss the different steps in the viral life cycle that are influenced by
IP6, and describe in detail how IP6 interacts with the immature and mature lattices
of different retroviruses.
acknowledgement: We thank Volker M. Vogt for his critical comments in preparation
of the review.
article_number: '1853'
article_processing_charge: Yes
article_type: original
author:
- first_name: Martin
full_name: Obr, Martin
id: 4741CA5A-F248-11E8-B48F-1D18A9856A87
last_name: Obr
orcid: 0000-0003-1756-6564
- 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: Robert A.
full_name: Dick, Robert A.
last_name: Dick
citation:
ama: Obr M, Schur FK, Dick RA. A structural perspective of the role of IP6 in immature
and mature retroviral assembly. Viruses. 2021;13(9). doi:10.3390/v13091853
apa: Obr, M., Schur, F. K., & Dick, R. A. (2021). A structural perspective of
the role of IP6 in immature and mature retroviral assembly. Viruses. MDPI.
https://doi.org/10.3390/v13091853
chicago: Obr, Martin, Florian KM Schur, and Robert A. Dick. “A Structural Perspective
of the Role of IP6 in Immature and Mature Retroviral Assembly.” Viruses.
MDPI, 2021. https://doi.org/10.3390/v13091853.
ieee: M. Obr, F. K. Schur, and R. A. Dick, “A structural perspective of the role
of IP6 in immature and mature retroviral assembly,” Viruses, vol. 13, no.
9. MDPI, 2021.
ista: Obr M, Schur FK, Dick RA. 2021. A structural perspective of the role of IP6
in immature and mature retroviral assembly. Viruses. 13(9), 1853.
mla: Obr, Martin, et al. “A Structural Perspective of the Role of IP6 in Immature
and Mature Retroviral Assembly.” Viruses, vol. 13, no. 9, 1853, MDPI, 2021,
doi:10.3390/v13091853.
short: M. Obr, F.K. Schur, R.A. Dick, Viruses 13 (2021).
date_created: 2021-10-07T09:13:29Z
date_published: 2021-09-17T00:00:00Z
date_updated: 2023-08-14T07:21:51Z
day: '17'
ddc:
- '616'
department:
- _id: FlSc
doi: 10.3390/v13091853
external_id:
isi:
- '000699841100001'
pmid:
- '34578434'
file:
- access_level: open_access
checksum: bcfd72a12977d48e22df3d0cc55aacf1
content_type: application/pdf
creator: cchlebak
date_created: 2021-10-08T10:38:15Z
date_updated: 2021-10-08T10:38:15Z
file_id: '10115'
file_name: 2021_Viruses_Obr.pdf
file_size: 4146796
relation: main_file
success: 1
file_date_updated: 2021-10-08T10:38:15Z
has_accepted_license: '1'
intvolume: ' 13'
isi: 1
issue: '9'
keyword:
- virology
- infectious diseases
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 26736D6A-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P31445
name: Structural conservation and diversity in retroviral capsid
publication: Viruses
publication_identifier:
issn:
- 1999-4915
publication_status: published
publisher: MDPI
quality_controlled: '1'
status: public
title: A structural perspective of the role of IP6 in immature and mature retroviral
assembly
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 13
year: '2021'
...