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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Microbiol. | doi: 10.3389/fmicb.2019.02438

Quantitative proteomics reveal peroxiredoxin perturbation upon persistent lymphocytic choriomeningitis virus infection in human cells

Martin Benej1,  Maksym Danchenko1, Ingrid Oveckova1, Filip Cervenak2,  Lubomir Tomaska2, Katarina Grossmannova1,  Katarina Polcicova1,  Tereza Golias1 and  Jana Tomaskova1*
  • 1Institute of Virology, Biomedical Research Center, Slovak Academy of Sciences, Slovakia
  • 2Department of Genetics, Faculty of Natural Sciences, Comenius University in Bratislava, Slovakia

Experimental data indicate that during persistent infection, lymphocytic choriomeningitis virus (LCMV) may both directly or indirectly modulate regulatory cellular processes and alter cellular functions that are not critical for survival, but are essential for cell homeostasis. In order to shed more light on these processes, two-dimensional differential in-gel electrophoresis (2D-DIGE) and MALDI-TOF tandem mass spectrometry were used to determine the proteome response of the HeLa cell line to persistent LCMV infection. Quantitative analysis revealed 24 differentially abundant proteins. Functional analysis showed that LCMV-responsive proteins were primarily involved in metabolism, stress, and the defense response. Among identified proteins, we discovered significant changes for peroxiredoxins, a family of antioxidant enzymes. Decreased amount of these antioxidant proteins correlated with elevation of reactive oxygen species (ROS) in infected cells. Increased levels of ROS were accompanied by changes in the pattern of telomeric restriction fragments in infected cells and mediated activation of hypoxia-inducible transcription factor-1 (HIF-1) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways. Moreover, treatment with antioxidants resulted in reduced levels of viral nucleoprotein, indicating a connection between ROS-dependent signaling and viral replication.

Keywords: LCMV (lymphocytic choriomeningitis virus), Arenavirus, host response, Proteomics, peroxiredoxin, ROS - reactive oxygen species, redox signaling, telomeres

Received: 26 Jul 2019; Accepted: 10 Oct 2019.

Copyright: © 2019 Benej, Danchenko, Oveckova, Cervenak, Tomaska, Grossmannova, Polcicova, Golias and Tomaskova. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Jana Tomaskova, Institute of Virology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, 814 38, Slovakia, jana.tomaskova@savba.sk