Membrane-Associated Flavivirus Replication Complex-Its Organization and Regulation.

Eiji Morita,Youichi Suzuki

doi:10.3390/v13061060

Eiji Morita, Youichi Suzuki

Open Access

https://doi.org/10.3390/v13061060

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Abstract

Flavivirus consists of a large number of arthropod-borne viruses, many of which cause life-threatening diseases in humans. A characteristic feature of flavivirus infection is to induce the rearrangement of intracellular membrane structure in the cytoplasm. This unique membranous structure called replication organelle is considered as a microenvironment that provides factors required for the activity of the flaviviral replication complex. The replication organelle serves as a place to coordinate viral RNA amplification, protein translation, and virion assembly and also to protect the viral replication complex from the cellular immune defense system. In this review, we summarize the current understanding of how the formation and function of membrane-associated flaviviral replication organelle are regulated by cellular factors.

Highlights

Flaviviruses are predominantly transmitted by mosquitoes and ticks and include clinically important viruses: Japanese encephalitis virus (JEV), dengue virus (DENV), yellow fever virus (YFV), West Nile virus (WNV), and tick-borne encephalitis virus (TBEV), which cause life-threatening diseases such as hemorrhagic fever, encephalitis, and meningitis in humans [1]
Of particular interest is that the intracellular membrane structure within the endoplasmic reticulum (ER) is rearranged by a virus infection, which is closely associated with the activity of the flaviviral replication complex, including viral RNA amplification and protein translation [12,13,14,15,16,17,18,19,20]
Studies of flavivirus infection by Tabata et al indicated that the depletion of Endosomal Sorting Complex Required for Transport (ESCRT) factors slightly affects virus genome replication, suggesting that the roles of ESCRT factors may commonly be involved in the vesicle packet (VP) formation of ssRNA(+) virus replication organelles

Summary

Introduction

The genus Flavivirus of the Flaviviridae family is a large virus group comprised of many emerging arthropod-borne pathogens. Of particular interest is that the intracellular membrane structure within the ER is rearranged by a virus infection, which is closely associated with the activity of the flaviviral replication complex, including viral RNA amplification and protein translation [12,13,14,15,16,17,18,19,20]. The establishment of this membranous microenvironment is thought to be necessary to promote flavivirus replication. We will focus our attention on the biogenesis and regulation of the flavivirus-induced organelle-like membranous structures by viral and cellular factors

Flavivirus Infection Rearranges Intracellular Membrane System and Creates

Viral Proteins Involved in the Formation of a Viral Replication Organelle

Cellular Autophagic Machinery Is Activated in the Flavivirus-Infected Cells

Flavivirus Infection Changes the Intracellular Membrane Lipid Composition

Findings

Conclusions