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Ultrastructural Localization and Molecular Associations of HCV Capsid Protein in Jurkat T Cells

Ultrastructural Localization and Molecular Associations of HCV Capsid Protein in Jurkat T Cells

Authors :
Cecilia Fernández-Ponce
Maria C. Durán-Ruiz
Isaac Narbona-Sánchez
Juan P. Muñoz-Miranda
Mikel M. Arbulo-Echevarria
Antonio Serna-Sanz
Christian Baumann
Rocío Litrán
Enrique Aguado
Wilhelm Bloch
Francisco García-Cozar
Source :
Frontiers in Microbiology, Vol 8 (2018)
Publication Year :
2018
Publisher :
Frontiers Media S.A., 2018.

Abstract

Hepatitis C virus core protein is a highly basic viral protein that multimerizes with itself to form the viral capsid. When expressed in CD4+ T lymphocytes, it can induce modifications in several essential cellular and biological networks. To shed light on the mechanisms underlying the alterations caused by the viral protein, we have analyzed HCV-core subcellular localization and its associations with host proteins in Jurkat T cells. In order to investigate the intracellular localization of Hepatitis C virus core protein, we have used a lentiviral system to transduce Jurkat T cells and subsequently localize the protein using immunoelectron microscopy techniques. We found that in Jurkat T cells, Hepatitis C virus core protein mostly localizes in the nucleus and specifically in the nucleolus. In addition, we performed pull-down assays combined with Mass Spectrometry Analysis, to identify proteins that associate with Hepatitis C virus core in Jurkat T cells. We found proteins such as NOLC1, PP1γ, ILF3, and C1QBP implicated in localization and/or traffic to the nucleolus. HCV-core associated proteins are implicated in RNA processing and RNA virus infection as well as in functions previously shown to be altered in Hepatitis C virus core expressing CD4+ T cells, such as cell cycle delay, decreased proliferation, and induction of a regulatory phenotype. Thus, in the current work, we show the ultrastructural localization of Hepatitis C virus core and the first profile of HCV core associated proteins in T cells, and we discuss the functions and interconnections of these proteins in molecular networks where relevant biological modifications have been described upon the expression of Hepatitis C virus core protein. Thereby, the current work constitutes a necessary step toward understanding the mechanisms underlying HCV core mediated alterations that had been described in relevant biological processes in CD4+ T cells.

Details

Language :
English
ISSN :
1664302X and 66178002
Volume :
8
Database :
Directory of Open Access Journals
Journal :
Frontiers in Microbiology
Publication Type :
Academic Journal
Accession number :
edsdoj.0b39c39b9fc24acebca66178002328b5
Document Type :
article
Full Text :
https://doi.org/10.3389/fmicb.2017.02595