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Biomedical subjects

R W Chamberlain

Publications and source records attributed to R W Chamberlain.

At least 19 recordsLinked to original sources

The complete coding sequence of hepatitis C virus genotype 5a, the predominant genotype in South Africa.

Hepatitis C virus (HCV) genotype 5a is the predominant genotype in southern Africa with a high prevalence amongst infected blood donors from areas in South Africa. We have determined the nucleotide sequence corresponding to the complete coding region of an HCV isolate, EUH1480, previously classified as genotype 5a, from an Edinburgh haemophiliac. The sequence contained a single open reading frame (ORF) coding for a polyprotein of 3014 amino acids. Comparison with the polyprotein sequences from other HCV genotypes, where the ORF varies from 3008 to 3037 amino acids, showed the observed variation in size was due to differences in lengths of the envelope 2 and the nonstructural 5A proteins. The sequence divergence of HCV genotype 5 ranged from 29.4% nucleotide differences (24.91% amino acid differences) compared with genotype 1c to 32.5% nucleotide differences (30.3% amino acid differences) compared with 2a. Phylogenetic analysis of the available full length nucleotide sequences showed EUH1480 to form a branch distinct from the other HCV types, confirming the classification of type 5a as a separate genotype.

Amino Acid Sequence↗

Complete coding sequence of hepatitis C virus genotype 6a.

Hepatitis C virus (HCV) genotype 6a is found in a restricted part of South East Asia, including Hong Kong, Macau and Vietnam. We determined the full length coding sequence of a type 6a isolate (EUHK2) obtained from a Hong Kong blood donor. The sequence of EUHK2 contained a single open reading frame coding for a polyprotein of 3018 amino acids, within the range of 3008 to 3037 for other HCV genotypes. The full length sequence of EUHK2 showed 30.3%-32.9% nucleotide (24.3%-29.4% amino acid) sequence divergence from genotypes 1-4, but only 27.7% (20.7% amino acid) divergence from JK046 ("type 11a"). These similarity values were intermediate between those of other HCV genotypes (minimum 28.4%) and between subtypes (maximum 25%). The close evolutionary relationship of EUHK2 with JK046 was further indicated by their grouping together by phylogenetic analysis.

Cloning, Molecular↗

Complete nucleotide sequence of a type 4 hepatitis C virus variant, the predominant genotype in the Middle East.

Hepatitis C virus (HCV) type 4 is the predominant genotype found throughout the Middle East and parts of Africa, often in association with high population prevalence as in Egypt. To investigate more fully its evolutionary relationship with other genotypes of HCV, and to study its overall genome organization, we have determined the entire sequence encompassing the coding region of the genotype 4a isolate ED43, obtained from an HCV-infected individual from Egypt. The sequence of ED43 contained a single open reading frame encoding a polyprotein of 3008 amino acids (aa), smaller than that reported for other HCV genotypes which vary from 3010 aa to 3037 aa. The nucleotide and amino acid sequences were compared with the full-length sequences already reported for genotypes 1a, 1b, 1c, 2a, 2b, 2c, 3a, 3b and those of isolates JKO49 and JKO46 described as types 10a and 11a. The differences in length of the polyprotein originated in variable regions in the E2 and NS5A genes. The complete sequence of ED43 confirmed the classification of type 4 as a separate major genotype.

Amino Acid Sequence↗

Recombinant capripoxvirus expressing the hemagglutinin protein gene of rinderpest virus: protection of cattle against rinderpest and lumpy skin disease viruses.

A cDNA clone containing the complete coding sequence of the hemagglutinin (H) protein gene of the RBOK vaccine strain of rinderpest virus, under the control of the vaccinia late promoter p11, was inserted by homologous recombination into the thymidine kinase gene of the KS-1 strain of capripoxvirus. The recombinant virus produced authentic H protein as judged by its electrophoretic mobility, transport to the cell surface of infected lamb testis cells, and reactivity with monoclonal antibodies specific for the H protein of rinderpest virus. The recombinant virus induced significant levels of rinderpest virus neutralizing antibodies in vaccinated cattle and protected them from clinical rinderpest after challenge with a lethal dose of a highly virulent heterologous strain of the virus. Protection was achieved using vaccine doses lower than those used with a similar recombinant expressing the fusion protein gene of rinderpest. The parental KS-1 virus is widely used as a vaccine against capripox viruses and so the rinderpest recombinant acts as a dual vaccine to protect cattle against both rinderpest and lumpy skin disease.

Animals↗

Nucleotide sequence comparisons of the fusion protein gene from virulent and attenuated strains of rinderpest virus.

We have cloned and sequenced the entire fusion (F) protein gene of the RBOK vaccine strain of rinderpest virus and the coding regions for the F genes of two mild field isolates of the virus from Africa. Analysis of the nucleotide and the predicted amino acid sequences showed that the vaccine virus was more than 99% identical in the protein coding region to the virulent Kabete O strain from which it was derived, whereas the field isolates differed by 10 to 12% from each other and from the vaccine strain. No changes were found in the F protein which could explain attenuation of the vaccine; however, each of the mild field isolates had amino acid changes in important functional areas which may be related to their attenuated phenotype.

Africa↗

Evidence for different lineages of rinderpest virus reflecting their geographic isolation.

Sequence analysis of part of the fusion protein gene from recent isolates of rinderpest virus revealed that distinct lineages of the virus exist which reflect the geographical location of their isolation in Africa and Asia. Current strains circulating in Kenya and Sudan were most similar, both in terms of nucleotide sequence and pathogenic nature, to viruses isolated in Egypt and in Nigeria in 1983/1984 and they were quite distinct from an East African isolate (RBT-1) from the 1960s. Two older isolates of the virus, the Japanese avianized/lapinized vaccine strain dating from the 1930s and the Old Kabete strain dating from 1911, each differed considerably from the other viruses. The sequence data were derived from the region where the precursor protein is cleaved to yield the biologically active F1/F2 heterodimer; all strains analysed had a highly basic connecting peptide which is required for efficient cleavage by endogenous host cell proteases. No correlation was found between amino acid changes at this site and the rinderpest virus pathogenicity unlike the association reported for Newcastle disease virus.

Africa↗

The epidemiology of St. Louis encephalitis in Dallas, Texas, 1966.

An epidemic of St. Louis encephalitis (SLE) occurred in Dallas, Texas, in the summer of 1966. A total of 545 suspected cases within Dallas city and county were reported, of which 145 were laboratory-confirmed as SLE virus infection. The greatest concentration of cases occurred in lower socioeconomic areas of the central part of the city in black populations. The attack rate and mortality rate increased markedly with age. The overall attack rate was 15.2 per 100,000, with a case fatality rate of 9.7%. During the course of the epidemic, most of the county was sprayed aerially with an ultra-low volume (ULV), high-concentration malathion mist. The effects of this treatment cannot be adequately assessed from the human epidemiologic aspect alone, but the spraying clearly reduced the number and infection rate of the vector mosquitoes.

Adolescent↗

The epidemiology of St. Louis encephalitis in Corpus Christi, Texas, 1966.

In the summer of 1966, an epidemic of St. Louis encephalitis occurred in Corpus Christi, Texas, coincident with one occurring in Dallas about 563 km to the north. Among the 76 cases confirmed in Corpus Christi, there were two deaths; the attack rate was 41.0 per 100,000. In contrast with a concurrent outbreak in Dallas and the 1964 outbreak in Houston, attack rates were much higher in populations of the upper socioeconomic districts. This distribution may have resulted from the combined effects of an unusual concentration of vector mosquito breeding sites in storm sewers in the upper socioeconomic districts and a higher degree of residual immunity in the residents of the lower socioeconomic areas.

Adolescent↗

Epidemiologic investigations of the 1969 epidemic of Venezuelan encephalitis in Ecuador.

An epizoodemic of Venezuelan equine encephalitis (VEE), subtype I variant B, occurred in Ecuador during the rainy and hot season of 1969. In this paper, a general description of the epidemic is given and virus isolations from humans are reported. A serologic survey was performed in order to determine the extension of the epidemic along the coastal zone of the country. It is not clear whether the higher antibody rate in older people was because they were at greater risk of infection or was the result of an accumulated immunity with time. The latter could be an indication of endemic virus activity, not yet proven for the VEE IB virus variant. Mosquito surveillance and attempted control by aerial spraying were carried out.

Adolescent↗