Role of RNA-binding proteins during the late stages of Flavivirus replication cycle

Abstract

The genus Flavivirus encompasses several worldwide-distributed arthropod-borne viruses including, dengue virus, Japanese encephalitis virus, West Nile virus, yellow fever virus, Zika virus, and tick-borne encephalitis virus. Infection with these viruses manifest with symptoms ranging from febrile illness to life-threatening hypotensive shock and encephalitis. Therefore, flaviviruses pose a great risk to public health. Currently, preventive measures are falling short to control epidemics and there are no antivirals against any Flavivirus. Flaviviruses carry a single stranded positive-sense RNA genome that plays multiple roles in infected cells: it is translated into viral proteins, used as template for genome replication, it is the precursor of the subgenomic flaviviral RNA and it is assembled into new virions. Furthermore, viral RNA genomes are also packaged into extracellular vesicles, e.g. exosomes, which represent an alternate mode of virus dissemination. Because RNA molecules are at the center of Flavivirus replication cycle, viral and host RNA-binding proteins (RBPs) are critical determinants of infection. Numerous studies have revealed the function of RBPs during Flavivirus infection, particularly at the level of RNA translation and replication. These proteins, however, are also critical participants at the late stages of the replication cycle. Here we revise the function of host RBPs and the viral proteins capsid, NS2A and NS3, during the packaging of viral RNA and the assembly of new virus particles. Furthermore, we go through the evidence pointing towards the importance of host RBPs in mediating cellular RNA export with the idea that the biogenesis of exosomes harboring Flavivirus RNA would follow an analogous pathway.

Investigating the human host - ssRNA virus interaction landscape using the SMEAGOL toolbox

“…The enrichment and depletion of RBP motifs in the SARS-CoV-2 genome is largely similar to that of the other coronaviruses in our dataset. However, it is unique in having strong enrichment for binding motifs of YBX1, which has been experimentally validated to bind to SARS-CoV-2 RNA 2 and supports infection by other viruses, including Dengue Virus 44 , Influenza 45 and HIV 46 . Like other coronaviruses, more RBPs were enriched and depleted (18 and 32 respectively) in the positive sense genome sequence compared to the negative sense intermediates (14 and 13 respectively), suggesting that more functional interactions happen with the positive sense molecule.…”

Dengue Immunopathogenesis: A Crosstalk between Host and Viral Factors Leading to Disease: Part I - Dengue Virus Tropism, Host Innate Immune Responses, and Subversion of Antiviral Responses

“…In addition to NS proteins, flavivirus sfRNAs have been described to regulate the innate immune responses via binding and inactivating RNA-binding proteins which are crucial for innate immunity [180,238]. DENV 3′UTRs possess RNA structures Please use Adobe Acrobat Reader to read this book chapter for free.…”

Capacity of a Multiplex IgM Antibody Capture ELISA to Differentiate Zika and Dengue Virus Infections in Areas of Concurrent Endemic Transmission

“…Their genomes encode a single polyprotein that is cleaved into structural (C, prM, and E) proteins that form the infectious virion containing the viral genome and nonstructural (NS1-NS5) proteins that are involved in virus replication. 12 During the acute phase of illness, both viruses present with similar clinical features, highlighting the need for accurate diagnostic tests. 13 The most reliable tests for distinguishing these viruses consist of nucleic acid detection in serum for DENV and serum, urine, and saliva for ZIKV.…”