Biomedical subjects

Alan D T Barrett

Publications and source records attributed to Alan D T Barrett.

48 records · Page 3Linked to original sources

PubMed2003

Crystallization and preliminary X-ray diffraction analysis of Langat virus envelope protein domain III.

The putative receptor-binding domain (domain III) of the flavivirus Langat envelope glycoprotein has been crystallized using the hanging-drop vapor-diffusion method at 277 K. Two distinct crystal morphologies were observed to grow under the same conditions. The crystal forms both belong to a trigonal space group, P3(1)21 or P3(2)21, with unit-cell parameters a = 80.93, c = 132.1 A and a = 104.8, c = 219.5 A for forms I and II, respectively. Complete data sets to 2.9 and 3.35 A, respectively, have been collected at 100 K with Cu Kalpha X-rays from a rotating-anode generator.

Chromatography, Gel↗

PubMed2003

Natural and nosocomial infection in a patient with West Nile encephalitis and extrapyramidal movement disorders.

Since its first recognition in North America in 1999, West Nile virus (WNV) has spread rapidly across the continent, but in many communities, rapid diagnostic tests for detection of WNV infection are not fully available. We describe a patient with extrapyramidal movement disorders and changes in the basal ganglia noted on magnetic resonance images that are characteristic of other flavivirus encephalitides and may help in the recognition of patients with West Nile encephalitis. Detailed molecular analysis suggested that, although our patient received a blood transfusion infected with WNV, the virus that caused his initial infection and encephalitis was probably acquired naturally from a mosquito.

Animals↗

PubMed2003

Limited evolution of West Nile virus has occurred during its southwesterly spread in the United States.

Analysis of partial nucleotide sequences of nine West Nile virus strains isolated in southeast Texas during June-August 2002 revealed a maximum of 0.35% nucleotide variation from a New York 1999 strain. Two sequence subtypes were identified that differed from each other by approximately 0.5%, suggesting multiple introductions of virus to this area. Analysis of sequences from cloned PCR products for one strain revealed up to 0.6% divergence from the consensus sequence at the subpopulation level. The presence of unique patterns of small numbers of mutations in North American West Nile strains studied to date may suggest the absence of a strong selective pressure to drive the emergence of dominant variants.

Animals↗

PubMed2003

Molecular characterization of a hamster viscerotropic strain of yellow fever virus.

A hamster viscerotropic strain of yellow fever (YF) virus has been derived after serial passage of strain Asibi through hamsters. The parental Asibi/hamster p0 virus causes a mild and transient viremia in hamsters with no outward, clinical signs of illness. In contrast, the viscerotropic Asibi/hamster p7 virus causes a robust viremia, severe illness, and death in subadult hamsters. The genome of the hamster viscerotropic Asibi/hamster p7 virus has been sequenced and compared with the parental nonviscerotropic Asibi/hamster p0 virus identifying 14 nucleotide changes encoding only seven amino acid substitutions. The majority of these substitutions (five of seven) fall within the envelope (E) protein at positions Q27H, D28G, D155A, K323R, and K331R. These results support an important role for the E protein in determining YF virus viscerotropism.

Amino Acid Substitution↗

PubMed2003

Origin and evolution of Japanese encephalitis virus in southeast Asia.

Since it emerged in Japan in the 1870s, Japanese encephalitis has spread across Asia and has become the most important cause of epidemic encephalitis worldwide. Four genotypes of Japanese encephalitis virus (JEV) are presently recognized (representatives of genotypes I to III have been fully sequenced), but its origin is not known. We have determined the complete nucleotide and amino acid sequence of a genotype IV Indonesian isolate (JKT6468) which represents the oldest lineage, compared it with other fully sequenced genomes, and examined the geographical distribution of all known isolates. JKT6468 was the least similar, with nucleotide divergence ranging from 17.4 to 19.6% and amino acid divergence ranging from 4.7 to 6.5%. It included an unusual series of amino acids at the carboxy terminus of the core protein unlike that seen in other JEV strains. Three signature amino acids in the envelope protein (including E327 Leu-->Thr/Ser on the exposed lateral surface of the putative receptor binding domain) distinguished genotype IV strains from more recent genotypes. Analysis of all 290 JEV isolates for which sequence data are available showed that the Indonesia-Malaysia region has all genotypes of JEV circulating, whereas only more recent genotypes circulate in other areas (P < 0.0001). These results suggest that JEV originated from its ancestral virus in the Indonesia-Malaysia region and evolved there into the different genotypes which then spread across Asia. Our data, together with recent evidence on the origins of other emerging viruses, including dengue virus and Nipah virus, imply that tropical southeast Asia may be an important zone for emerging pathogens.

Amino Acid Sequence↗

PubMed2003

Genetic variation among temporally and geographically distinct West Nile virus isolates, United States, 2001, 2002.

Analysis of partial nucleotide sequences of 22 West Nile virus (WNV) isolates collected during the summer and fall of 2001 and 2002 indicated genetic variation among strains circulating in geographically distinct regions of the United States and continued divergence from isolates collected in the northeastern United States during 1999 and 2000. Sequence analysis of a 2,004-nucleotide region showed that 14 isolates shared two nucleotide mutations and one amino acid substitution when they were compared with the prototype WN-NY99 strain, with 10 of these isolates sharing an additional nucleotide mutation. In comparison, isolates collected from coastal regions of southeast Texas shared the following differences from WN-NY99: five nucleotide mutations and one amino acid substitution. The maximum nucleotide divergence of the 22 isolates from WN-NY99 was 0.35% (mean = 0.18%). These results show the geographic clustering of genetically similar WNV isolates and the possible emergence of a dominant variant circulating across much of the United States during 2002.

Base Sequence↗

PubMed2003

West Nile virus in Mexico: evidence of widespread circulation since July 2002.

West Nile virus (WNV) antibodies were detected in horses from five Mexican states, and WNV was isolated from a Common Raven in the state of Tabasco. Phylogenetic studies indicate that this isolate, the first from Mexico, is related to strains from the central United States but has a relatively high degree of sequence divergence.

Animals↗

PubMed2002

Mouse neuroinvasive phenotype of West Nile virus strains varies depending upon virus genotype.

Despite recent advances in the genetics of West Nile (WN) virus, relatively little is known about the molecular basis of virulence of this virus. In particular, although the genotype of the WN virus strain that was recently introduced into North America has been determined, there have been few experimental studies on the virulence phenotype of the virus. We compared genetic and neurovirulence properties of 19 strains of WN virus, including 2 from North America, and observed significant differences in their neuroinvasive phenotype in mice and hamsters that correlated with virus genotype. Virus isolated in North America was found to be highly neuroinvasive with a lack of age-related resistance to infection in mice normally associated with mosquito-borne flaviviruses.

Age Factors↗

PubMed2002

The epidemiology of yellow fever in Africa.

Yellow fever (YF) is still a major public heath problem, particularly in Africa, despite the availability of a very efficacious vaccine. The World Health Organization estimates that there are 200,000 cases of YF annually, including 30,000 deaths, of which over 90% occur in Africa. In the past 15 years, the number of YF cases has increased tremendously, with most of the YF activity in West Africa. This increase in YF activity is in part due to a breakdown in YF vaccination and mosquito control programs. Five genotypes of YF virus have been found in Africa, and each genotype circulates in a distinct geographical region. West Africa genotype I, found in Nigeria and surrounding areas, is associated with frequent epidemics, whereas the three genotypes in East and Central Africa are in regions where YF outbreaks are rare. Other factors, including genetic and behavioral variation among vector species, are also thought to play a role in the epidemiology of YF in Africa.

Aedes↗

PubMed2002

Identification of neutralizing epitopes within structural domain III of the West Nile virus envelope protein.

Using a panel of neutralizing monoclonal antibodies, we have mapped epitopes in domain III of the envelope protein of the New York strain of West Nile virus. The ability of monoclonal antibodies that recognize these epitopes to neutralize virus appeared to differ between lineage I and II West Nile virus strains, and epitopes were located on the upper surface of domain III at residues E307, E330, and E332.

Animals↗

PubMed2002

Arilvax (PowderJect).

Celltech (formerly Medeva) had developed Arilvax, a single-dose, live, attenuated vaccine for the prevention of yellow fever, which the company launched in Europe. However, in October 2000, PowderJect acquired the vaccine as part of its acquisition of Celltech's vaccine business [381557], [384374]. In July 2001, PowderJect expected to re-launch Arilvax in the UK and, in the near future, Europe, following a manufacturing upgrade [414453], [443490]. By May 2000, Acambis (formerly Peptide Therapeutics), was developing the vaccine in the US under an exclusive license and phase III trials were underway [341301], [366663]. By September 2000, preparation for a BLA in the US had begun [382969]. By September 2001, the BLA submission was expected by mid-2002 [422760], [443490]. In September 1999, Peptide Therapeutics was predicting a US launch in the first half of 2001 with expected sales of around US $25 million per annum [340078], [341301].

Animals↗

PubMed2001

Phylogeny of the Simbu serogroup of the genus Bunyavirus.

The Simbu serogroup of the genus Bunyavirus, family Bunyaviridae contains 25 viruses. Previous serological studies provided important information regarding some but not all of the relationships among Simbu serogroup viruses. This report describes the nucleotide sequence determination of the nucleocapsid (N) gene of the small genomic segment of 14 Simbu serogroup viruses and partial nucleotide sequence determination of the G2 glycoprotein-coding region (encoded by the medium RNA segment) of 19 viruses. The overall phylogeny of the Simbu serogroup inferred from analyses of the N gene was similar to that inferred from analyses of the G2 protein-coding region. Both analyses revealed that the Simbu serogroup viruses have evolved into at least five major phylogenetic lineages. In general, these phylogenetic lineages were consistent with the previous serological data, but provided a more detailed understanding of the relatedness amongst many viruses. In comparison to previous phylogenetic studies on the California and Bunyamwera serogroups of the Bunyavirus genus, the Simbu serogroup displays much larger genetic variation in the N gene (up to 40% amino acid sequence divergence).

Nucleocapsid↗