Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein. Academic Article uri icon

Overview

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.

publication date

  • December 20, 2017

Research

keywords

  • DEAD-box RNA Helicases
  • Lymphocytic choriomeningitis virus
  • Models, Molecular
  • RNA-Dependent RNA Polymerase
  • Repressor Proteins
  • Ribonucleoproteins
  • Viral Proteins

Identity

PubMed Central ID

  • PMC5738113

Scopus Document Identifier

  • 85039912180

Digital Object Identifier (DOI)

  • 10.1371/journal.ppat.1006758

PubMed ID

  • 29261807

Additional Document Info

volume

  • 13

issue

  • 12