Abstract
Flaviviruses are vector-borne RNA viruses, many of which are clinically relevant human viral pathogens, such as dengue, Zika, Japanese encephalitis, West Nile and yellow fever viruses. Millions of people are infected with these viruses around the world each year. Vaccines are only available for some members of this large virus family, and there are no effective antiviral drugs to treat flavivirus infections. The unmet need for vaccines and therapies against these flaviviral infections drives research towards a better understanding of the epidemiology, biology and immunology of flaviviruses. In this review, we discuss the basic biology of the flavivirus replication process and focus on the molecular aspects of viral genome replication. Within the virus-induced intracellular membranous compartments, flaviviral RNA genome replication takes place, starting from viral poly protein expression and processing to the assembly of the virus RNA replication complex, followed by the delivery of the progeny viral RNA to the viral particle assembly sites. We attempt to update the latest understanding of the key molecular events during this process and highlight knowledge gaps for future studies.
Highlights
One large clade of known viruses is the positive-sense single-stranded RNA (+ssRNA)virus class, which belongs to group IV in the Baltimore classification [1]
There is no effective vaccine or antiviral drug to treat dengue virus, despite continuing efforts to develop one. These viruses induce the formation of mini-organelles associated with the endoplasmic reticulum, which act as viral RNA replication factories
We focus on the molecular structures of the nonstructural proteins and their interactions with each other and RNA, as well as the ultrastructural characterisation of the complex by electron microscopy and tomography
Summary
One large clade of known viruses is the positive-sense single-stranded RNA (+ssRNA). virus class, which belongs to group IV in the Baltimore classification [1]. These viruses include many important human pathogens, such as rhinoviruses, coronaviruses and flaviviruses The genome of these viruses has the same polarity as the messenger RNA of the host cell, allowing it to take advantage of cellular mechanisms and be readily translated into protein [2]. There is no effective vaccine or antiviral drug to treat dengue virus, despite continuing efforts to develop one During infection, these viruses induce the formation of mini-organelles associated with the endoplasmic reticulum, which act as viral RNA replication factories. These viruses induce the formation of mini-organelles associated with the endoplasmic reticulum, which act as viral RNA replication factories Within these replication organelles (ROs), multiple viral and host factors combine to form the RNA replicase machinery, known as replication complex (RC). We focus on the molecular structures of the nonstructural proteins and their interactions with each other and RNA, as well as the ultrastructural characterisation of the complex by electron microscopy and tomography
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