---
_id: '540'
abstract:
- lang: eng
text: RNA-dependent RNA polymerases (RdRps) play a key role in the life cycle of
RNA viruses and impact their immunobiology. The arenavirus lymphocytic choriomeningitis
virus (LCMV) strain Clone 13 provides a benchmark model for studying chronic infection.
A major genetic determinant for its ability to persist maps to a single amino
acid exchange in the viral L protein, which exhibits RdRp activity, yet its functional
consequences remain elusive. To unravel the L protein interactions with the host
proteome, we engineered infectious L protein-tagged LCMV virions by reverse genetics.
A subsequent mass-spectrometric analysis of L protein pulldowns from infected
human cells revealed a comprehensive network of interacting host proteins. The
obtained LCMV L protein interactome was bioinformatically integrated with known
host protein interactors of RdRps from other RNA viruses, emphasizing interconnected
modules of human proteins. Functional characterization of selected interactors
highlighted proviral (DDX3X) as well as antiviral (NKRF, TRIM21) host factors.
To corroborate these findings, we infected Trim21-/-mice with LCMV and found impaired
virus control in chronic infection. These results provide insights into the complex
interactions of the arenavirus LCMV and other viral RdRps with the host proteome
and contribute to a better molecular understanding of how chronic viruses interact
with their host.
article_number: e1006758
author:
- first_name: Kseniya
full_name: Khamina, Kseniya
last_name: Khamina
- first_name: Alexander
full_name: Lercher, Alexander
last_name: Lercher
- first_name: Michael
full_name: Caldera, Michael
last_name: Caldera
- first_name: Christopher
full_name: Schliehe, Christopher
last_name: Schliehe
- first_name: Bojan
full_name: Vilagos, Bojan
last_name: Vilagos
- first_name: Mehmet
full_name: Sahin, Mehmet
last_name: Sahin
- first_name: Lindsay
full_name: Kosack, Lindsay
last_name: Kosack
- first_name: Anannya
full_name: Bhattacharya, Anannya
last_name: Bhattacharya
- first_name: Peter
full_name: Májek, Peter
last_name: Májek
- first_name: Alexey
full_name: Stukalov, Alexey
last_name: Stukalov
- first_name: Roberto
full_name: Sacco, Roberto
id: 42C9F57E-F248-11E8-B48F-1D18A9856A87
last_name: Sacco
- first_name: Leo
full_name: James, Leo
last_name: James
- first_name: Daniel
full_name: Pinschewer, Daniel
last_name: Pinschewer
- first_name: Keiryn
full_name: Bennett, Keiryn
last_name: Bennett
- first_name: Jörg
full_name: Menche, Jörg
last_name: Menche
- first_name: Andreas
full_name: Bergthaler, Andreas
last_name: Bergthaler
citation:
ama: Khamina K, Lercher A, Caldera M, et al. Characterization of host proteins interacting
with the lymphocytic choriomeningitis virus L protein. PLoS Pathogens.
2017;13(12). doi:10.1371/journal.ppat.1006758
apa: Khamina, K., Lercher, A., Caldera, M., Schliehe, C., Vilagos, B., Sahin, M.,
… Bergthaler, A. (2017). Characterization of host proteins interacting with the
lymphocytic choriomeningitis virus L protein. PLoS Pathogens. Public Library
of Science. https://doi.org/10.1371/journal.ppat.1006758
chicago: Khamina, Kseniya, Alexander Lercher, Michael Caldera, Christopher Schliehe,
Bojan Vilagos, Mehmet Sahin, Lindsay Kosack, et al. “Characterization of Host
Proteins Interacting with the Lymphocytic Choriomeningitis Virus L Protein.” PLoS
Pathogens. Public Library of Science, 2017. https://doi.org/10.1371/journal.ppat.1006758.
ieee: K. Khamina et al., “Characterization of host proteins interacting with
the lymphocytic choriomeningitis virus L protein,” PLoS Pathogens, vol.
13, no. 12. Public Library of Science, 2017.
ista: Khamina K, Lercher A, Caldera M, Schliehe C, Vilagos B, Sahin M, Kosack L,
Bhattacharya A, Májek P, Stukalov A, Sacco R, James L, Pinschewer D, Bennett K,
Menche J, Bergthaler A. 2017. Characterization of host proteins interacting with
the lymphocytic choriomeningitis virus L protein. PLoS Pathogens. 13(12), e1006758.
mla: Khamina, Kseniya, et al. “Characterization of Host Proteins Interacting with
the Lymphocytic Choriomeningitis Virus L Protein.” PLoS Pathogens, vol.
13, no. 12, e1006758, Public Library of Science, 2017, doi:10.1371/journal.ppat.1006758.
short: K. Khamina, A. Lercher, M. Caldera, C. Schliehe, B. Vilagos, M. Sahin, L.
Kosack, A. Bhattacharya, P. Májek, A. Stukalov, R. Sacco, L. James, D. Pinschewer,
K. Bennett, J. Menche, A. Bergthaler, PLoS Pathogens 13 (2017).
date_created: 2018-12-11T11:47:03Z
date_published: 2017-12-01T00:00:00Z
date_updated: 2021-01-12T08:01:48Z
day: '01'
ddc:
- '576'
- '616'
department:
- _id: GaNo
doi: 10.1371/journal.ppat.1006758
file:
- access_level: open_access
checksum: 1aa20f19a1e90664fadce6e7d5284fdc
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:12:26Z
date_updated: 2020-07-14T12:46:44Z
file_id: '4944'
file_name: IST-2018-931-v1+1_journal.ppat.1006758.pdf
file_size: 4106772
relation: main_file
file_date_updated: 2020-07-14T12:46:44Z
has_accepted_license: '1'
intvolume: ' 13'
issue: '12'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
publication: PLoS Pathogens
publication_identifier:
issn:
- '15537366'
publication_status: published
publisher: Public Library of Science
publist_id: '7276'
pubrep_id: '931'
quality_controlled: '1'
scopus_import: 1
status: public
title: Characterization of host proteins interacting with the lymphocytic choriomeningitis
virus L protein
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 13
year: '2017'
...