Abstract
Flaviviruses are emerging and re-emerging arthropod-borne pathogens responsible for significant mortality and morbidity worldwide. The genus comprises more than seventy small, positive-sense, single-stranded RNA viruses, which are responsible for a spectrum of human and animal diseases ranging in symptoms from mild, influenza-like infection to fatal encephalitis and haemorrhagic fever. Despite genomic and structural similarities across the genus, infections by different flaviviruses result in disparate clinical presentations. This review focusses on two haemorrhagic flaviviruses, dengue virus and yellow fever virus, and two neurotropic flaviviruses, Japanese encephalitis virus and Zika virus. We review current knowledge on host-pathogen interactions, virus entry strategies and tropism.
Highlights
The Flavivirus genus consists of more than 70 small, positive-sense, single-stranded RNA viruses transmitted by arthropods, in particular mosquitos and ticks
Glycoprotein E is responsible for receptor-mediated attachment of flaviviruses to the host cell and membrane fusion
E protein of different flaviviruses share approximately 40% sequence identity (e.g., dengue virus (DENV) and tick-borne encephalitis virus (TBEV)), their overall structural features are almost identical and this is assumed to apply to all flaviviruses [166]
Summary
The Flavivirus genus consists of more than 70 small, positive-sense, single-stranded RNA viruses transmitted by arthropods, in particular mosquitos and ticks These include globally important human pathogens such as West Nile virus (WNV), Japanese encephalitis virus (JEV), dengue virus (DENV), Murray Valley encephalitis virus (MVE), tick-borne encephalitis virus (TBEV), Yellow Fever virus (YFV), and Zika virus (ZIKV). Dendritic cells migrate to lymphoid organs where viral replication takes place allowing for flavivirus dissemination into circulation and internal organs [12] Viruses such DENV [27], JEV [28], ZIKV [29] have been shown to infect skin dendritic cells, and there are no reports on YFV infecting Langerhans cells, it can infect other types of dendritic cells [30]. For this review we will focus on four major flaviviruses of humans—DENV, JEV, ZIKV, and YFV, and discuss the differences and similarities in their mechanisms of entry into arthropod and mammalian cells
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