The Host Factor Erlin-1 is Required for Efficient Hepatitis C Virus Infection
by
Christina Whitten-Bauer 1,†, Josan Chung 1,†, Andoni Gómez-Moreno 2, Pilar Gomollón-Zueco 2, Michael D. Huber 3,‡, Larry Gerace 3 and Urtzi Garaigorta 1,2,*
Christina Whitten-Bauer 1,†, Josan Chung 1,†, Andoni Gómez-Moreno 2, Pilar Gomollón-Zueco 2, Michael D. Huber 3,‡, Larry Gerace 3 and Urtzi Garaigorta 1,2,*
1
Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, CA 92037, USA
2
Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología Consejo Superior de Investigaciones Científicas (CNB-CSIC), 28049 Madrid, Spain
3
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
*
Author to whom correspondence should be addressed.
†
Equal contribution.
‡
Current address: Vividion Therapeutics, San Diego, CA 92121, USA.
Cells 2019, 8(12), 1555; https://doi.org/10.3390/cells8121555
Received: 28 October 2019 / Revised: 28 November 2019 / Accepted: 29 November 2019 / Published: 2 December 2019
(This article belongs to the Special Issue Cell Biology of Viral Infections)
Development of hepatitis C virus (HCV) infection cell culture systems has permitted the identification of cellular factors that regulate the HCV life cycle. Some of these cellular factors affect steps in the viral life cycle that are tightly associated with intracellular membranes derived from the endoplasmic reticulum (ER). Here, we describe the discovery of erlin-1 protein as a cellular factor that regulates HCV infection. Erlin-1 is a cholesterol-binding protein located in detergent-resistant membranes within the ER. It is implicated in cholesterol homeostasis and the ER-associated degradation pathway. Silencing of erlin-1 protein expression by siRNA led to decreased infection efficiency characterized by reduction in intracellular RNA accumulation, HCV protein expression and virus production. Mechanistic studies revealed that erlin-1 protein is required early in the infection, downstream of cell entry and primary translation, specifically to initiate RNA replication, and later in the infection to support infectious virus production. This study identifies erlin-1 protein as an important cellular factor regulating HCV infection.
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Keywords:
hepatitis C virus; HCV; erlin-1; erlin-2; host factor; endoplasmic reticulum; RNA replication; protein production; virus production; lipid droplet
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MDPI and ACS Style
Whitten-Bauer, C.; Chung, J.; Gómez-Moreno, A.; Gomollón-Zueco, P.; Huber, M.D.; Gerace, L.; Garaigorta, U. The Host Factor Erlin-1 is Required for Efficient Hepatitis C Virus Infection. Cells 2019, 8, 1555.
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