Compartmentalized replication organelle of flavivirus at the ER and the factors involved

Yali Ci,Lei Shi

doi:10.1007/s00018-021-03834-6

Abstract

Flaviviruses are positive-sense single-stranded RNA viruses that pose a considerable threat to human health. Flaviviruses replicate in compartmentalized replication organelles derived from the host endoplasmic reticulum (ER). The characteristic architecture of flavivirus replication organelles includes invaginated vesicle packets and convoluted membrane structures. Multiple factors, including both viral proteins and host factors, contribute to the biogenesis of the flavivirus replication organelle. Several viral nonstructural (NS) proteins with membrane activity induce ER rearrangement to build replication compartments, and other NS proteins constitute the replication complexes (RC) in the compartments. Host protein and lipid factors facilitate the formation of replication organelles. The lipid membrane, proteins and viral RNA together form the functional compartmentalized replication organelle, in which the flaviviruses efficiently synthesize viral RNA. Here, we reviewed recent advances in understanding the structure and biogenesis of flavivirus replication organelles, and we further discuss the function of virus NS proteins and related host factors as well as their roles in building the replication organelle.

Highlights

RNA viruses pose a great threat to human beings
Considering the different structures and formation mechanisms, we focus on flavivirus replication organelles in the present review
Flavivirus-induced compartmentalized replication organelles derived from the endoplasmic reticulum (ER) are a characteristic cellular hallmark, and are the prerequisite and essential structural basis of flavivirus replication

Summary

Introduction

RNA viruses pose a great threat to human beings. Many well-known viruses, such as influenza virus, HIV, dengue virus (DENV), rabies virus, poliovirus and the current global epidemic SARS-CoV-2, are RNA viruses. Keywords Flavivirus · Replication organelle · ER rearrangement · Compartmentalization · Membrane remodeling · Nonstructural proteins · Host factors Some factors participate in this ER reorganization process during flavivirus replication, including viral proteins, host proteins and lipids. Considering the rareness of the invaginated vesicular structure at the ER under physiological conditions, the assumption that flavivirus-encoded proteins play dominant roles establishing viral replication organelles is reasonable.

Results

Conclusion