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Annual Review of Virology

Volume 2, 2015

Flaviviridae Replication Organelles: Oh, What a Tangled Web We Weave

Abstract

Replication of positive-strand RNA viruses occurs in tight association with reorganized host cell membranes. In a concerted fashion, viral and cellular factors generate distinct organelle-like structures, designated viral replication factories. These virus-induced compartments promote highly efficient genome replication, allow spatiotemporal coordination of the different steps of the viral replication cycle, and protect viral RNA from the hostile cytoplasmic environment. The combined use of ultrastructural and functional studies has greatly increased our understanding of the architecture and biogenesis of viral replication factories. Here, we review common concepts and distinct differences in replication organelle morphology and biogenesis within the Flaviviridae family, exemplified by dengue virus and hepatitis C virus. We discuss recent progress made in our understanding of the complex interplay between viral determinants and subverted cellular membrane homeostasis in biogenesis and maintenance of replication factories of this virus family.

Keyword(s): dengue virus, double-membrane vesicle, hepatitis C virus, membrane modification, positive-strand RNA virus, virus-host interactions

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2015-11-09
2024-04-19
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Flaviviridae Replication Organelles: Oh, What a Tangled Web We Weave
Annual Review of Virology 2, 289 (2015); https://doi.org/10.1146/annurev-virology-100114-055007
/content/journals/10.1146/annurev-virology-100114-055007
/content/journals/10.1146/annurev-virology-100114-055007
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Supplemental Material

    Morphology of dengue virus (DV) replication organelles. Electron tomography with 3D reconstruction reveals the continuity of endoplasmic reticulum membranes () and DV-induced vesicular invaginations. Budding of DV progeny virions () juxtaposed to vesicle openings is frequently observed. Golgi membranes are depicted in green. Adapted with permission from Welsch et al., 5:365–75 (2009).

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    Morphology of hepatitis C virus (HCV) replication organelles consisting primarily of double-membrane vesicles (DMVs). Color-coded 3D surface model shows outer membranes of DMVs in light brown and inner membranes in orange. DMVs emerge as protrusions from the endoplasmic reticulum () and are thus commonly found to be connected to this compartment. Small single-membrane vesicles are depicted in pink, intermediate filaments in dark blue, and Golgi membranes in green. Reproduced with permission from Romero-Brey et al., . 8:e1003056 (2012).

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  • Article Type: Review Article

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