RESUMO
We analyzed the 186,102 base pairs (bp) that constitute the entire DNA genome of a highly virulent variola virus isolated from Bangladesh in 1975. The linear, double-stranded molecule has relatively small (725 bp) inverted terminal repeat (ITR) sequences containing three 69-bp direct repeat elements, a 54-bp partial repeat element, and a 105-base telomeric end-loop that can be maximally base-paired to contain 17 mismatches. Proximal to the right-end ITR sequences are another seven 69-bp elements and a 53- and a 27-bp partial element. Sequence analysis showed 187 closely spaced open reading frames specifying putative major proteins containing > or = 65 amino acids. Most of the virus proteins correspond to proteins in current databases, including 150 proteins that have > 90% identity to major gene products encoded by vaccinia virus, the smallpox vaccine. Variola virus has a group of proteins that are truncated compared with vaccinia virus counterparts and a smaller group of proteins that are elongated. The terminal regions encode several novel proteins and variants of other poxvirus proteins that potentially augment variola virus transmissibility and virulence for its only natural host, humans.
Assuntos
Genoma Viral , Varíola/microbiologia , Vírus da Varíola/genética , Animais , Bangladesh , Sequência de Bases , Embrião de Galinha , Pré-Escolar , Sequência Conservada , DNA Viral , Feminino , Variação Genética , Humanos , Dados de Sequência Molecular , Fases de Leitura Aberta , Proteínas Quinases/genética , Receptores de Citocinas/genética , Sequências Repetitivas de Ácido Nucleico , Mapeamento por Restrição , Especificidade da Espécie , Vírus da Varíola/classificação , Vírus da Varíola/isolamento & purificação , Vírus da Varíola/patogenicidade , Proteínas do Envelope Viral/genética , Proteínas Virais/genéticaRESUMO
Smallpox eradication culminated the most successful antimicrobial campaign in medical history. To characterize further the linear double-stranded DNA genome of the aetiological agent of smallpox, we have determined the entire nucleotide sequence of the highly virulent variola major virus, strain Bangladesh-1975 (VAR-BSH; 186,102 base pairs, 33.7% G + C; Genbank accession number, L22579). Here we highlight features of the molecule and focus on a few of the 187 putative proteins that probably contribute to pathogenicity and virus host-range properties. One hundred and fifty proteins were markedly similar to those of vaccinia virus (smallpox vaccine), for which a complete sequence has been reported for strain Copenhagen (VAC-CPN; 191,636 base pairs, 33.3% G + C). The remaining 37 proteins reflected variola-specific sequences or open reading frame divergences for variant proteins, which are often truncated or elongated compared with their vaccinia counterparts.
