The 5′ and 3′ Untranslated Regions of the Flaviviral Genome

Abstract

Flaviviruses are enveloped arthropod-borne viruses with a single-stranded, positive-sense RNA genome that can cause serious illness in humans and animals. The 11 kb 5′ capped RNA genome consists of a single open reading frame (ORF), and is flanked by 5′ and 3′ untranslated regions (UTR). The ORF is a polyprotein that is processed into three structural and seven non-structural proteins. The UTRs have been shown to be important for viral replication and immune modulation. Both of these regions consist of elements that are essential for genome cyclization, resulting in initiation of RNA synthesis. Genome mutation studies have been employed to investigate each component of the essential elements to show the necessity of each component and its role in viral RNA replication and growth. Furthermore, the highly structured 3′UTR is responsible for the generation of subgenomic flavivirus RNA (sfRNA) that helps the virus evade host immune response, thereby affecting viral pathogenesis. In addition, changes within the 3′UTR have been shown to affect transmissibility between vector and host, which can influence the development of vaccines.

Long non‐coding subgenomic flavivirus RNAs have extended 3D structures and are flexible in solution

“…Flaviviruses are enveloped RNA viruses with singlestranded, positive sense genomic RNA (gRNA) of approximately 10-11 kb in length which consists of a single open reading frame (ORF) flanked by highly structured 5 0 and 3 0 untranslated regions (UTR). The 5 0 UTR, 3 0 UTR, and capsid coding sequences are highly structured and contain many cis-acting elements which are involved in gRNA replication, translation, and perhaps encapsidation [9][10][11]. The 5 0 UTR, 3 0 UTR, and capsid coding sequences are highly structured and contain many cis-acting elements which are involved in gRNA replication, translation, and perhaps encapsidation [9][10][11].…”

“…The ORF encodes a polyprotein which is cotranslationally and/or posttranslationally processed into three structural proteins (capsid, pre-membrane/membrane, and envelope) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) [9]. The 5 0 UTR, 3 0 UTR, and capsid coding sequences are highly structured and contain many cis-acting elements which are involved in gRNA replication, translation, and perhaps encapsidation [9][10][11].…”

Artificial MicroRNA-Mediated Inhibition of Japanese Encephalitis Virus Replication in Neuronal Cells

“…The 3¢UTR has been shown to be necessary for viral replication and immune modulation. This region consists of elements that are essential for genome cyclization, resulting in the initiation of RNA synthesis [15]. In addition to the critical role 3¢UTR plays on RNA synthesis, the stem-loop structure of 3¢UTR is also responsible for the generation of subgenomic flavivirus RNA (sfRNA).…”

Viral replicons as valuable tools for drug discovery

“…The polyprotein is then processed by the viral NS2b/3 and cellular proteases into the three structural proteins Capsid, pre-Membrane and Envelope, and the seven nonstructural (NS) proteins NS1, NS2a, NS2b, NS3, NS4a, NS4b and NS5, with NS5 harbouring N-terminal methyltransferase and C-terminal RdRp activity. In addition to the 5 0 and 3 0 UTRs, the first 65 nucleotides of the Capsid coding region contain a hairpin element and the 5 0 cyclisation motif, which are essential for replication [39]. A DENV2 replicon was established by Pang et al in 2001 by deletion of pre-Membrane and Envelope protein coding regions, showing that DENV is amenable to analysis by replicons [40].…”