Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein

Khamina, Kseniya and Lercher, Alexander and Caldera, Michael and Schliehe, Christopher and Vilagos, Bojan and Sahin, Mehmet and Kosack, Lindsay and Bhattacharya, Anannya and Májek, Peter and Stukalov, Alexey and Sacco, Roberto and James, Leo C. and Pinschewer, Daniel D. and Bennett, Keiryn L. and Menche, Jörg and Bergthaler, Andreas. (2017) Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein. PLoS Pathogens, 13 (12). e1006758.

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Medical Microbiology > Experimental Virology (Pinschewer)
UniBasel Contributors:Pinschewer, Daniel
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Public Library of Science
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:20 Aug 2020 14:51
Deposited On:20 Aug 2020 14:51

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