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The crystallographically determined structure of a soluble fragment from the major envelope protein of a flavivirus reveals an unusual architecture. The flat, elongated dimer extends in a direction that would be parallel to the viral membrane. Residues that influence binding of monoclonal antibodies lie on the outward-facing surface of the protein. The(More)
The prediction of the complete matrix of base pairing probabilities was applied to the 3' noncoding region (NCR) of flavivirus genomes. This approach identifies not only well-defined secondary structure elements, but also regions of high structural flexibility. Flaviviruses, many of which are important human pathogens, have a common genomic organization,(More)
Flaviviruses assemble in the endoplasmic reticulum by a mechanism that appears to be driven by lateral interactions between heterodimers of the envelope glycoproteins E and prM. Immature intracellular virus particles are then transported through the secretory pathway and converted to their mature form by cleavage of the prM protein by the cellular protease(More)
MicroRNAs (miRNAs) are a class of small, non-coding RNAs that play a pivotal role in the regulation of posttranscriptional gene expression in a wide range of eukaryotic organisms. Although DNA viruses have been shown to encode miRNAs and exploit the cellular RNA silencing machinery as a convenient way to regulate viral and host gene expression, it is(More)
We introduce here a heuristic approach to kinetic RNA folding that constructs secondary structures by stepwise combination of building blocks. These blocks correspond to subsequences and their thermodynamically optimal structures. These are determined by the standard dynamic programming approach to RNA folding. Folding trajectories are modeled at base-pair(More)
Infectious cDNA clones of two strains of tick-borne encephalitis (TBE) virus, i.e. European subtype prototypic strain Neudoerfl and the closely related but more virulent strain Hypr, were constructed. The recombinant constructs consisted of cDNAs stably inserted into the bacterial plasmid pBR322 under the control of T7 promoter elements. The genome of TBE(More)
The entire genomic sequences of two strains (Hypr and 263) of the flavivirus tick-borne encephalitis (TBE) virus differing in virulence from the prototypic strain Neudoerfl were determined. Strain Hypr is a human isolate of TBE virus with a high laboratory passage history which exhibits a significantly higher neuro-invasiveness in mice compared to the(More)
By the use of limited trypsin digestion of purified virions, we generated a membrane anchor-free and crystallizable form of the tick-borne encephalitis virus envelope glycoprotein E. It retained its reactivity with a panel of monoclonal antibodies, and only subtle structural differences from the native protein E were recognized. Treatment with the(More)
The timing of vaccine availability is essential for an effective response to pandemic influenza. In 2009, vaccine became available after the disease peak, and this has motivated the development of next generation vaccine technologies for more rapid responses. The SAM(®) vaccine platform, now in pre-clinical development, is based on a synthetic,(More)
Obtaining suitable seed viruses for influenza vaccines poses a challenge for public health authorities and manufacturers. We used reverse genetics to generate vaccine seed-compatible viruses from the 2009 pandemic swine-origin influenza virus. Comparison of viruses recovered with variations in residues 186 and 194 (based on the H3 numbering system) of the(More)