Figure 1 Three-dimensional cryo-electron microscopic reconstructions of immature (left) and mature (right) particles of an isolate of dengue virus (courtesy of M. Rossmann). Shown is a surface rendering of immature dengue virus at 12.5A resolution (left) and mature DENV at 10A resolution (right). The viruses are depicted to scale, but not colored to scale. Triangles outline one icosahedral unit.

Figure 2 Flavivirus genome organization (not to scale) and polyprotein processing. The virion RNA is about 11 kb in size. At the top is the viral genome with the structural and nonstructural protein coding regions and the 5′- and 3′-NCRs. Boxes below the genome indicate viral proteins generated by the proteolytic processing cascade. P, H, and R symbols indicate the localization of the NS3 protease, the NS3 RNA helicase, and the NS5 RdRp, respectively.

Figure 3 Negative contrast electron micrograph of particles of an isolate of bovine viral diarrhea virus 1. The bar represents 100 nm.

(From M. König, with permission.)

Figure 4 Pestivirus genome organization (not to scale) and polyprotein processing. The RNA is usually about 12.3 kb in size (depending on the virus). The 5′-NCR is about 370–385 nt, the ORF about 11.7 kb and the 3′-NCR is 185-273 nt. The viral nonstructural proteins are indicated as NS. P′, P″, P′″, H and R symbols indicate the localization of the N^pro protease, the NS2 protease, the NS3 protease, the NS3 RNA helicase and the NS5B RdRp, respectively. The proteases and proteolytic steps involved in the generation of individual proteins are indicated. In noncp BVD viruses, NS2-3 cleavage is detectable only for a short time early after infection. In cp BVD viruses, NS3 is produced continuously in addition to NS2-3.

Figure 5 Hepacivirus genome organization (not to scale) and polyprotein processing. For species Hepatitis C virus, the RNA is about 9.6 kb in size. The 5′-NCR is about 340 nt, the 3′-NCR is about 250 nt, and the ORF is about 9 kb. The species HCV has a p7 protein between E2 and NS2; the other possible member of the genus, GB virus B, has a p13 protein, which can be cleaved into p7 and p6. The host and viral proteases involved in cleavage of the polyprotein are indicated. The cleavage by host signal peptide peptidase (at the C-terminus of core) is indicated by an open arrow; the cleavages by host signal peptidase (remaining sites) are indicated by filled arrows. The locations of the NS2-3 protease, NS3 protease, NS3 RNA helicase and NS5B RdRp are indicated by P′, P″, H and R, respectively.

Figure 6 Phylogeny of the conserved sequences in the RdRp (NS5 or NS5B) of classified members of the family Flaviviridae. Partial gene sequences (292 aa, positions 7704–8550 numbered as in the HCV-1 genome, AF011751) from the representative strains listed in each table. CLUSTALW was used to create a multiple alignment for the aa sequences which was verified by alignment of the known motifs in the region. An unrooted phylogenetic tree was constructed from the sequence alignment by neighbor-joining of (uncorrected) amino acid p-distances using the MEGA version 4.1 package. The virus names corresponding to the abbreviations can be found in the “List of species” in each genus. Note that the Entebbe virus group comprising Entebbe bat virus, Sokoluk virus and Yokose virus have no known vector but group phylogenetically within the mosquito-borne flaviviruses. Nounané, Chaoyang, Ngoye and Lammi viruses are not currently assigned to a specific virus group but also group within the mosquito-borne viruses.