The newest updates on Falvivirus...
Mass Cataloging of Flaviviruses - This group recently published a new platform technology through which Flaviviruses can now be cataloged using mass spectrometry. The technology has been shown to work through identification of two correctly identified strains of Dengue virus and the technology looks optimistic for West Nile, Japanese encephalitis, and Yellow Fever viruses. The technology can also distinguish major sub-groups within strain type and can easily be transported to remote locations for rapid, efficacious tracking of new flavivirus outbreaks.
Reference: George W. Jackson, Roger J. McNichols, George E. Fox and Richard C. Willson. “Toward Universal Flavivirus Identification by Mass Cataloging.” Journal of Molecular Diagnostics 2008, Vol. 10, No. 2. Published online before print February 7, 2008.
Flavi Viral Entry - Viral entry of flaviviruses into the host cell are mediated by a fusion peptide 16 amino acids long located in the second domain of enveolope protein E. This study looked at multiple different types of flaviviruses and found that while 27% of these viruses had mutations in general, contrastingly, there were very few mutations in the cannonical region of this particular peptide sequence.
Reference: Stephen J Seligman. “Constancy and diversity in the flavivirus fusion peptide.” Virology Journal 2008, 5:27.
West Nile Virus Replication - Through biochemical anlysis, this study has found that the methyltransferase of West Nile Virues has a binding site, SAM, which donates methyl groups to both the N7 and 2'-O positions of the viral RNA cap. Methylation of both of these sties is necessary for viral replication and therefore they present a site through which replication could be halted for flavivirus therapy.
Reference: Hongping Dong, Suping Ren, Bo Zhang, Yangsheng Zhou, Francesc Puig-Basagoiti, Hongmin Li, and Pei-Yong Shi1. “West Nile Virus Methyltransferase catalyzes Two Methylations 1 of the Viral RNA Cap 2 through a Substrate Repositioning Mechanism” Journal of Virology [epub ahead of print]. 27 February 2008.
Flavi Replication - During replication the RNA genome of flaviviruses is known to circularize. On both the 3' and 5' ends of Flaviviruses there are two complmentary regions known as the 5'–3'CS and 5'–3'UAR
that have been proposed to complementarily bind to one another in order to allow circularization to take place. The 5'–3'CS region has been shown in dengue and other mosquito viruses to be required for replication, however, this study tested the necessity of the
5'–3'UAR for replication. The study found that without this region replication was interrupted and even if nucleotides were compensationally replaced on the other strand, structures of
secondary proteins also important in replication were still
inhibited.
Reference: Diego E. Alvareza, Claudia V. Filomatoria and Andrea V. Gamarnik. “Functional analysis of dengue virus cyclization sequences located at the 5' and 3'UTRs.” Journal of Virology [epub ahead of print]. 5 March 2008.
DENG-1 Replication- Flaviviruses have two N-glycosylation sites that are thought to be important for viral replication. In this experiement, Dengue virus 1 was mutated at one of these two sties, by switching the Asn nucleotide at bp 130 to an Ala nucleotide. After mutation DENG-1 was found to be unable to replicate in both mosquito and mammelian cells This finding may be pretinant in the development of a vaccine in the future.
Reference: Shigeru Tajima, Tomohiko Takasaki, and Ichiro Kurane. Characterization of Asn130-to-Ala mutant of dengue type 1 virus NS1 protein. Virus Genes [epub ahead of print]. 21 Feb 2008.
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