کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4361308 1616212 2011 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Adeno-Associated Virus 2 Infection Requires Endocytosis through the CLIC/GEEC Pathway
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی میکروب شناسی
پیش نمایش صفحه اول مقاله
Adeno-Associated Virus 2 Infection Requires Endocytosis through the CLIC/GEEC Pathway
چکیده انگلیسی

SummaryAdeno-associated viruses (AAVs) are nonpathogenic, nonenveloped, single-stranded DNA viruses in development as gene therapy vectors. AAV internalization was postulated to proceed via a dynamin-dependent endocytic mechanism. Revisiting this, we find that infectious endocytosis of the prototypical AAV, AAV2, is independent of clathrin, caveolin, and dynamin. AAV2 infection is sensitive to EIPA, a fluid-phase uptake inhibitor, but is unaffected by Rac1 mutants or other macropinocytosis inhibitors. In contrast, AAV2 infection requires actin cytoskeleton remodeling and membrane cholesterol and is sensitive to inhibition of Cdc42, Arf1, and GRAF1, factors known to be involved in the formation of clathrin-independent carriers (CLIC). AAV2 virions are internalized in the detergent-resistant GPI-anchored-protein-enriched endosomal compartment (GEEC) and translocated to the Golgi apparatus, similarly to the CLIC/GEEC marker cholera toxin B. Our results indicate that—unlike the viral entry mechanisms described so far—AAV2 uses the pleiomorphic CLIC/GEEC pathway as its major endocytic infection route.

Graphical AbstractFigure optionsDownload high-quality image (307 K)Download as PowerPoint slideHighlights
► AAV2 infection is independent of clathrin, caveolin, dynamin, or macropinocytosis
► AAV2 infection is dependent on actin and cholesterol
► The infectious entry of AAV2 proceeds through clathrin-independent carriers (CLIC)
► AAV2 is internalized in GPI-anchored-protein-enriched endosomal compartments (GEECs)

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 10, Issue 6, 15 December 2011, Pages 563–576
نویسندگان
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