The Dengue Virus Replication Complex: From RNA Replication to Protein-Protein Interactions to Evasion of Innate Immunity

Advances in Experimental Medicine and Biology
Julien LescarSiew Pheng Lim

Abstract

Viruses from the Flavivirus family are the causative agents of dengue fever, Zika, Japanese encephalitis, West Nile encephalitis or Yellow fever and constitute major or emerging public health problems. A better understanding of the flavivirus replication cycle is likely to offer new opportunities for the design of antiviral therapies to treat severe conditions provoked by these viruses, but it should also help reveal fundamental biological mechanisms of the host cell. During virus replication, RNA synthesis is mediated by a dynamic and membrane-bound multi-protein assembly, named the replication complex (RC). The RC is composed of both viral and host-cell proteins that assemble within vesicles composed of the endoplasmic reticulum membrane, near the nucleus. At the heart of the flavivirus RC lies NS4B, a viral integral membrane protein that plays a role in virulence and in down-regulating the innate immune response. NS4B binds to the NS2B-NS3 protease-helicase, which itself interacts with the NS5 methyl-transferase polymerase. We present an overview of recent structural and functional data that augment our understanding of how viral RNA is replicated by dengue virus. We focus on structural data that illuminate the various roles...Continue Reading

Citations

Nov 7, 2019·Antimicrobial Agents and Chemotherapy·L Albentosa-GonzálezA Mas
Jan 26, 2020·Vaccines·Carolina Coronel-RuizJuan C Zapata
Jan 15, 2019·Current Medicinal Chemistry·Preeti KarwalPratibha Kumari
Sep 18, 2020·Vaccines·Rosa C Coldbeck-ShackleyMichael R Beard
Feb 2, 2021·Frontiers in Microbiology·Alessandra RomanoFrancesco Gonella
May 22, 2020·ACS Medicinal Chemistry Letters·Rolando CannalireGiuseppe Manfroni
Jul 3, 2021·Life·Rong ZhaoJimin Cao
Jan 1, 2019·Antiviral Research·Siew Pheng Lim

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