کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4361786 1301421 2007 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cholesterol Manipulation by West Nile Virus Perturbs the Cellular Immune Response
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی میکروب شناسی
پیش نمایش صفحه اول مقاله
Cholesterol Manipulation by West Nile Virus Perturbs the Cellular Immune Response
چکیده انگلیسی

SummaryComplex membrane structures induced by West Nile virus (WNV), an enveloped RNA virus, are required for efficient viral replication. How these membranes are induced and how they facilitate the viral life cycle are unknown. We show that WNV modulates host cell cholesterol homeostasis by upregulating cholesterol biosynthesis and redistributing cholesterol to viral replication membranes. Manipulating cholesterol levels and altering concentrations of cellular geranylgeranylated proteins had a deleterious effect on virus replication. Depletion of the key cholesterol-synthesizing enzyme 3-hydroxy-methyglutaryl-CoA reductase drastically hampered virus replication. Significantly, virus-induced redistribution of cellular cholesterol downregulated the interferon-stimulated Jak-STAT antiviral signaling response to infection. This defect could be partially restored by exogenous addition of cholesterol, which increased the ability of infected cells to respond to interferon. We propose that, by manipulating cellular cholesterol, WNV utilizes the cellular response to cholesterol deficiency and dependence of antiviral signaling pathways on cholesterol-rich microdomains to facilitate viral replication and survival.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 2, Issue 4, 11 October 2007, Pages 229–239
نویسندگان
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