Disease relevance of Flavivirus

• The polyprotein also has significant sequence similarity to helicases encoded by animal pestiviruses, plant potyviruses, and human flaviviruses, and it contains sequence motifs widely conserved among viral replicases and trypsin-like proteases [1].
• Expression of the resistant allele of Oas1b in susceptible embryo fibroblasts resulted in partial inhibition of the replication of a flavivirus but not of an alpha togavirus [2].
• Antibody-dependent enhancement (ADE), a phenomenon in which viral replication is increased rather than decreased by immune sera, has been observed in vitro for a large number of viruses of public health importance, including flaviviruses, coronaviruses, and retroviruses [3].
• Intriguingly, the bNLS is highly conserved among Dengue and related flaviviruses, implying a general role for the region and importin beta in the infectious cycle [4].
• The structure of the RNA and the encoded polyprotein had properties similar to known flaviviruses and pestiviruses [5].

High impact information on Flavivirus

• The positions of these sites have demonstrated that E2 forms the protruding spikes and that E1 must be long and narrow, lying flat on the viral surface, forming an icosahedral scaffold analogous to the arrangement of the E glycoprotein in flaviviruses [6].
• Evidence is presented that M phi complement receptors (CR3) mediate IgM-dependent enhancement of flavivirus replication in the presence of complement [7].
• An RNA cap (nucleoside-2'-O-)-methyltransferase in the flavivirus RNA polymerase NS5: crystal structure and functional characterization [8].
• Flavivirus premembrane protein cleavage and spike heterodimer secretion require the function of the viral proteinase NS3 [9].
• These detailed atomic interactions provide the first structural insights into the inhibition of a viral enzyme by ribavirin 5'-triphosphate, as well as the basis for rational drug design of antiviral agents with improved specificity against the emerging flaviviruses [10].

Chemical compound and disease context of Flavivirus

• The RNA-dependent RNA polymerase NS5 of flaviviruses presents a characteristic motif of S-adenosyl-L-methionine-dependent methyltransferases at its N-terminus, and polymerase motifs at its C-terminus [8].
• We have undertaken a mutational analysis of the region of NS3 which contains the catalytic serine, five putative substrate binding residues, and several residues that are highly conserved among flavivirus proteases and among all serine proteases [11].
• The ts lesion of ts25 was shown to be due to a single alanine substitution for Arg-299, a residue which is conserved among flaviviruses [12].
• The data presented thus suggest the existence of structurally related interactions of the flavivirus and alphavirus fusion proteins with cholesterol in the molecular processes required for fusion but, at the same time, point to significant differences between the class II fusion machineries of these viruses [13].
• Characterization of the purified HCV NTPase activity showed that it exhibited reaction condition optima with respect to pH, MgCl2, and salt identical to those of the representative pestivirus and flavivirus enzymes [14].

Biological context of Flavivirus

• Structure of a flavivirus envelope glycoprotein in its low-pH-induced membrane fusion conformation [15].
• Yellow fever virus (YFV), a member of the Flavivirus genus, has a plus-sense RNA genome encoding a single polyprotein [16].
• Analysis of murine major histocompatibility complex class II-restricted T-cell responses to the flavivirus Kunjin by using vaccinia virus expression [17].
• Langat flavivirus protease NS3 binds caspase-8 and induces apoptosis [18].
• BVDV and related flaviviruses use the host ER as the primary site of envelope glycoprotein biogenesis, genomic replication, and particle assembly [19].

Anatomical context of Flavivirus

• In vivo, prM cleavage was blocked by a furin inhibitor, and infection of the furin-deficient cell line LoVo yielded only immature virions, suggesting that furin is essential for cleavage activation of flaviviruses [20].
• Analysis of murine CD8(+) T-cell clones specific for the Dengue virus NS3 protein: flavivirus cross-reactivity and influence of infecting serotype [21].
• It was only the combined pretreatment with IFN-alpha/beta and pIC that elicited strong antiviral responses that completely prevented flavivirus replication in macrophages from susceptible mice [22].
• Early E-selectin, VCAM-1, ICAM-1, and late major histocompatibility complex antigen induction on human endothelial cells by flavivirus and comodulation of adhesion molecule expression by immune cytokines [23].
• Hybridomas defining three different antibody-combining sites (epitopes) on the glycoprotein of TBE virus were selected on the basis of cross-reactivity with another flavivirus [24].

Gene context of Flavivirus

• Effective interferon (IFN) responses are critical to recovery from infection with flaviviruses, and the mosquito-borne flaviviruses can inhibit this response [25].
• This study further supports that anti-CYP2A6 in the absence of flavivirus is rather limited to APS-1 [26].
• Ig-CAM and MHC-1 expression on undifferentiated ES cells was not up-regulated by treatment of cells with interferon-gamma (IFN-gamma), tumor necrosis factor alpha, or flavivirus infection, agents that up-regulate these molecules in other embryonic cell types [27].
• We deduced the boundaries of each protein in the polyprotein sequence according to the protein cleavage sites of other flaviviruses [28].
• In accordance with this finding, the putative cleavage sites of the TABV polyprotein by the virus protease are substantially different from those of flaviviruses [29].

Analytical, diagnostic and therapeutic context of Flavivirus

• A new vaccination principle against flaviviruses, based on a tick-borne encephalitis virus (TBEV) self-replicating noninfectious RNA vaccine that produces subviral particles, has recently been introduced (R. M. Kofler, J. H. Aberle, S. W. Aberle, S. L. Allison, F. X. Heinz, and C. W. Mandl, Proc. Natl. Acad. Sci. USA 7:1951-1956, 2004) [30].
• The flavivirus nonstructural glycoprotein NS1 is highly conserved and contains two N-linked glycosylation sites which are both utilized for addition of oligosaccharides during replication in cell culture [31].
• The Focus Technologies IgM ELISA had a sensitivity and a specificity of 99.3% (excluding the non-WNV flavivirus sera) [32].
• Gene mapping and positive identification of the non-structural proteins NS2A, NS2B, NS3, NS4B and NS5 of the flavivirus Kunjin and their cleavage sites [33].
• The reverse-transcriptase PCR (RT-PCR) successfully amplified flavivirus sequences from cell cultures, frozen brain tissue, and formalin-fixed, paraffin-embedded brain tissue [34].

References