Evidence is presented to show that variola and monkeypox viruses evolved independently from a common ancestor. An open reading frame (ORF), potentially coding for a protein of 341 amino acid residues, was found to be conserved in two strains of variola virus (Harvey and Somalia), but degenerate in the Denmark strain of monkeypox virus. Monkeypox virus had a deletion of 391 bp, two 24bp deletions and a single base pair deletion within the coding region of this single copy ORF. The ORF corresponds to the E5R ORF in the published sequence of the Copenhagen strain of vaccinia virus, and the DNA sequence was determined for an additional strain of vaccinia virus, Dairen. A number of other Orthopoxviruses were found to contain this ORF, strengthening confidence in its presence in an ancestral Orthopoxvirus. The equivalent DNA sequence was determined for a number of monkeypox virus strains from West and Central Africa. The Denmark strain was identical to one from Liberia, indicating that this virus probably originated from West Africa. A third virus from West Africa, Benin, was found to have >99% base similarity and the same pattern of deletions as the other two monkeypox viruses. The Zaire strains were identical to one another and different from the West African strains. Like the West African strains, they contained the two 24bp deletions and single base pair deletion. In place of the large deletion they had three smaller deletions of 5-, 9- and 127-bp as well as a single base pair insertion. They also had additional deletions of land 2-bp and an insertion of 3bp. The West African strains have the potential to code for a truncated gene product of 107 amino acid residues, whereas the Zaire strains have no significant ORF. This clearly shows that monkeypox virus has diverged into two geographically isolated groups (Zaire and West Africa). There was >99% base similarity between the two groups, suggesting that the divergence occurred recently. Phylogenetic analysis, by the neighbour-joining method, was undertaken on the corresponding DNA sequences from variola (2 strains), monkeypox (6 strains), vaccinia (1 strain + 2 published sequences), cowpox (2 strains), taterapox, camel pox and ectromelia viruses. For every species gerbilpox virus was the nearest neighbour, suggesting that taterapox virus may be the species most closely related to the common ancestral Orthopoxvirus. Within the variola and cowpox virus species there was >99% DNA sequence conservation. Between species, camelpox virus was the most closely related species to gerbilpox virus, with variola virus, and, more distantly, vaccinia virus, falling into the same group. Cowpox virus was the most diverged species examined. Ectromelia virus shared a branch with cowpox virus. A comparison was made of the intergenic DNA sequence between this ORF and the adjacent downstream ORF. Variation was found, both within and between species, in the form of insertions and deletions. The interrelationships between the different Orthopoxvirus species more or less parallels that of the E5R-equivalent comparison. Some of the viruses had clusters of direct repeats. A pentameric repeated unit was found in 2, 10 and 17 copies in camelpox, gerbilpox and ectromelia viruses respectively. Raccoon poxvirus had a 7bp unit in 13 adjacent copies. The two cowpox viruses had a more complex arrangement of repeated sequences. It was thought that the ESR ORF may prove to be nonessential for virus replication. This was tested by interruption of the E5R gene in vaccinia virus; this did not affect the ability of the virus to form plaques in cell culture, but appeared to reduce the pathogenicity of the 'virus for rabbits. The deduced amino acid sequences were analysed for conserved and variable regions within the gene, to which no specific function has yet been assigned.

Thesis (M.A.) -- University of Texas Southwestern Medical Center at Dallas, 2004. / Vita. Bibliography: 71-73.

OLIVEIRA, Carla Silvino de. Cidade (in) salubre: idéias e práticas médicas em Fortaleza - (1838-1853). 2007. 156 f. Dissertação (Mestrado em História) - Universidade Federal do Ceará, Departamento de História, Programa de Pós-Graduação em História Social, Fortaleza-ce, 2007. / Submitted by Raul Oliveira (raulcmo@hotmail.com) on 2012-06-22T14:05:17Z No. of bitstreams: 1 2007_Dis_CSOliveira.pdf: 2924100 bytes, checksum: 7d99551b0ba52fb41a7986feffd54b96 (MD5) / Approved for entry into archive by Maria Josineide Góis(josineide@ufc.br) on 2012-06-25T11:44:34Z (GMT) No. of bitstreams: 1 2007_Dis_CSOliveira.pdf: 2924100 bytes, checksum: 7d99551b0ba52fb41a7986feffd54b96 (MD5) / Made available in DSpace on 2012-06-25T11:44:34Z (GMT). No. of bitstreams: 1 2007_Dis_CSOliveira.pdf: 2924100 bytes, checksum: 7d99551b0ba52fb41a7986feffd54b96 (MD5) Previous issue date: 2007 / The following work analizes the ideas and the medical practice, mainly the ones from José Lourenço de Castro Silva and Liberato de Castro Carreira, the first Cearence doctors graduated at Rio de Janeiro medical shcool, working in Fortaleza since 1838. It states the starting point of the medical actions influenced by social medicine, in which it thinks over the day-to-day actions considering the desease and the unhealthy city. The medical actions put into effect are the following: the creation and organization of urban areas(graveyards, hospitas, markets, penitenciary), the preventive orientation and the healing of the deseases, mainly the epidemics of smallpox in 1845 and yellow fever from 1851 to 1853. In this study, the main sources used were The Description of epidemics of yellow fever in the province of Ceará State in 1851 and 1852 by Castro Carreira, from Rio de Janeiro National Library: forms and medical manuals, from the Unicamp central library: medical and presidential forms, laws, correspondences, diverse documents belonging to the Ceará State Public Archive (APEC), and also documents from the Governor Menezes Pimentel Public Library. / O trabalho analisa as idéias e práticas médicas, principalmente as de José Lourenço de Castro e Silva e Liberato de Castro Carreira, primeiros médicos cearenses formados pela Faculdade de Medicina do Rio de Janeiro, com atuação em Fortaleza, a partir do ano de 1838. Marca o início da ação médica influenciada pela medicina social, a qual (re)pensa as práticas do cotidiano diante da doença e da cidade (in)salubre. As ações médicas possibilitam: a criação e organização dos espaços urbanos (cemitério, hospital, mercado, cadeia), a orientação preventiva e de cura das doenças, principalmente as epidemias de varíola em 1845, e febre amarela nos anos de 1851 a 1853. No estudo foram utilizadas como fontes principais a obra do Castro Carreira Descripção da epidemia da febre amarella na Província do Ceará em 1851 e 1852. da Biblioteca Nacional do Rio de Janeiro, Formulários e guias médicos da Biblioteca Central da Unicamp, além de Relatórios médicos e presidenciais, Leis, Correspondências, documentos diversos pertencentes ao acervo do Arquivo Público do Estado do Ceará – APEC e da Biblioteca Pública Governador Menezes Pimentel - CE.