--- res: bibo_abstract: - 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.@eng bibo_authorlist: - foaf_Person: foaf_givenName: Kseniya foaf_name: Khamina, Kseniya foaf_surname: Khamina - foaf_Person: foaf_givenName: Alexander foaf_name: Lercher, Alexander foaf_surname: Lercher - foaf_Person: foaf_givenName: Michael foaf_name: Caldera, Michael foaf_surname: Caldera - foaf_Person: foaf_givenName: Christopher foaf_name: Schliehe, Christopher foaf_surname: Schliehe - foaf_Person: foaf_givenName: Bojan foaf_name: Vilagos, Bojan foaf_surname: Vilagos - foaf_Person: foaf_givenName: Mehmet foaf_name: Sahin, Mehmet foaf_surname: Sahin - foaf_Person: foaf_givenName: Lindsay foaf_name: Kosack, Lindsay foaf_surname: Kosack - foaf_Person: foaf_givenName: Anannya foaf_name: Bhattacharya, Anannya foaf_surname: Bhattacharya - foaf_Person: foaf_givenName: Peter foaf_name: Májek, Peter foaf_surname: Májek - foaf_Person: foaf_givenName: Alexey foaf_name: Stukalov, Alexey foaf_surname: Stukalov - foaf_Person: foaf_givenName: Roberto foaf_name: Sacco, Roberto foaf_surname: Sacco foaf_workInfoHomepage: http://www.librecat.org/personId=42C9F57E-F248-11E8-B48F-1D18A9856A87 - foaf_Person: foaf_givenName: Leo foaf_name: James, Leo foaf_surname: James - foaf_Person: foaf_givenName: Daniel foaf_name: Pinschewer, Daniel foaf_surname: Pinschewer - foaf_Person: foaf_givenName: Keiryn foaf_name: Bennett, Keiryn foaf_surname: Bennett - foaf_Person: foaf_givenName: Jörg foaf_name: Menche, Jörg foaf_surname: Menche - foaf_Person: foaf_givenName: Andreas foaf_name: Bergthaler, Andreas foaf_surname: Bergthaler bibo_doi: 10.1371/journal.ppat.1006758 bibo_issue: '12' bibo_volume: 13 dct_date: 2017^xs_gYear dct_isPartOf: - http://id.crossref.org/issn/15537366 dct_language: eng dct_publisher: Public Library of Science@ dct_title: Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein@ ...