Flavivirus

Basic information and current topics regarding Flaviviridae

Expression and Biosynthesis

General Characteristics of the Flavivirus Genome:

The flavivirus genome is composed of one single stranded, positive sense RNA that consists of about 11kb’s. The genome encodes one single polyproptein that is cleaved after translation. This cleavage makes 10 total proteins; 3 structural (C, prM, and E), and 7 non-structural (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5).  The 5’ end of the RNA strand is capped, but does not have a poly-A tail.  Their RNA encodes one open reading frame (ORF), with untranslated regions (UTR’s) on both the 3’ and 5’ end.  The structural proteins of flaviviruses are located on the 5’ end of the genome, and the non-structural proteins are found on the 3’ end1.

Picture 1: Depiction of flavivirus genome, including structural and non-strucutal proteins.  Image from expasy.org (See references for full citation).

Picture 2:  Depiction of the flavivirus structure, as well as the single open reading frame that eventually gets cleaved into both structural and non-structural proteins.  Image from Basic Virology: Replication Patterns of Specific Viruses – at http://www.blackwellpublishing.com. (See reference for full citation).

Genome Replication

Once the virus fuses with the endosome, the genome  is released into the cytoplasm, where it functions as an mRNA.  At the rough ER, translation of the open reading frame occurs, and makes one large polyprotien.  This is polyprotein is cleaved  into separate, mature proteins after translation including, NS5 – the viral RdRP1.  After translation occurs, synthesis of viral RNA takes place in viral complexes, with the production of a (-)-strand of RNA serving as the template strand.  After the template strand is made, many more (+) strand RNA’s are made, which make up the genome of what will soon be the progeny of the flavivirus that came into the cell and began replicating!  An interesting finding is that is takes about 15 minutes for progeny RNA synthesis to be made2!

References:

Picture 1: Viral Zone: Flavivirus. Accessed April 2, 2011. Expert Protein Analysis System.
<http://expasy.org/viralzone/all_by_species/24.html&gt;

Picture 2: Wagner, E., Hewlett, M. (2004). Black Publishing Company. Basic Virology: Replication Patterns of Specific Viruses. p .242.  Accessed online: March 28, 2011 <http://www.blackwellpublishing.com/wagner/015.pdf&gt;

1.  Villardo, S.M., Gamarnik, A.V. (2009).  Genome Cyclization as Strategy for Flavivirus  RNA Replication.  Virus Research. 139:230-239

2.  Chambers, T. J., & Monath, T. P. (2003). The Flaviviruses: Structure, replication, and evolution. p. 100.