--- _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' ...