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Ernest A Gould

Publications and source records attributed to Ernest A Gould.

17 recordsLinked to original sources
PubMed2006

Genetic characterization of tick-borne flaviviruses: new insights into evolution, pathogenetic determinants and taxonomy.

Here, we analyze the complete coding sequences of all recognized tick-borne flavivirus species, including Gadgets Gully, Royal Farm and Karshi virus, seabird-associated flaviviruses, Kadam virus and previously uncharacterized isolates of Kyasanur Forest disease virus and Omsk hemorrhagic fever virus. Significant taxonomic improvements are proposed, e.g. the identification of three major groups (mammalian, seabird and Kadam tick-borne flavivirus groups), the creation of a new species (Karshi virus) and the assignment of Tick-borne encephalitis and Louping ill viruses to a unique species (Tick-borne encephalitis virus) including four viral types (i.e. Western Tick-borne encephalitis virus, Eastern Tick-borne encephalitis virus, Turkish sheep Tick-borne encephalitis virus and Louping ill Tick-borne encephalitis virus). The analyses also suggest a complex relationship between viruses infecting birds and those infecting mammals. Ticks that feed on both categories of vertebrates may constitute the evolutionary bridge between the three distinct identified lineages.

Animals↗
PubMed2006

Detection of seroconversion to West Nile virus, Usutu virus and Sindbis virus in UK sentinel chickens.

We previously reported evidence of West Nile virus (WNV) circulation in UK birds, probably introduced by migratory birds from overseas. We now demonstrate WNV-specific seroconversion in sentinel chickens raised on an English farm. Maternal neutralizing antibodies to WNV in hatchlings declined within three weeks. During the following months, healthy chickens developed WNV neutralizing antibodies that were confirmed by immunoblotting and indirect immunofluorescence tests using WNV antigens. The proportion of seropositive chickens was higher for WNV than for Usutu virus or Sindbis virus. Attempts to isolate infectious virus or to detect viral RNA in the sera, failed.

Alphavirus Infections↗
PubMed2005

Nonviremic transmission of West Nile virus.

West Nile virus (WNV) is now the predominant circulating arthropod-borne virus in the United States with >15,000 human cases and >600 fatalities since 1999. Conventionally, mosquitoes become infected when feeding on viremic birds and subsequently transmit the virus to susceptible hosts. Here, we demonstrate nonviremic transmission of WNV between cofeeding mosquitoes. Donor, Culex pipiens quinquefasciatus mosquitoes infected with WNV were fed simultaneously with uninfected "recipient" mosquitoes on naïve mice. At all times, donor and recipient mosquitoes were housed in separate sealed containers, precluding the possibility of mixing. Recipients became infected in all five trials, with infection rates as high as 5.8% and no detectable viremia in the hosts. Remarkably, a 2.3% infection rate was observed when 87 uninfected mosquitoes fed adjacent to a single infected mosquito. This phenomenon could potentially enhance virus survival, transmission, and dispersion and obviate the requirement for viremia. All vertebrates, including immune and insusceptible animals, might therefore facilitate mosquito infection. Our findings question the status of dead-end hosts in the WNV transmission cycle and may partly explain the success with which WNV established and rapidly dispersed throughout North America.

Animal Feed↗
PubMed2005

Virus evolution during a severe dengue epidemic in Cuba, 1997.

Full-length genomic sequences from six DENV-2 isolates sampled at different times during a dengue outbreak that occurred in Cuba in 1997 were determined. Phylogenetic analysis indicated that these isolates fall into the "American/Asian" genotype. Genome analysis revealed strong conservation of the structural proteins and the non-coding regions (5' NCR and 3' NCR). Nucleotide substitutions were observed in non-structural genes and most notably in the NS5 gene. There was a clear pattern of virus evolution during the epidemic; the earliest isolates sampled differed from those sampled later by amino acid replacements in the NS1 and NS5 proteins, although there was no evidence that these represented escape mutants. Further studies are therefore required to define the functional role of amino acid replacements observed and their possible relation to disease severity.

Aedes↗
PubMed2004

Complete genome analysis and molecular characterization of Usutu virus that emerged in Austria in 2001: comparison with the South African strain SAAR-1776 and other flaviviruses.

Here we describe the complete genome sequences of two strains of Usutu virus (USUV), a mosquito-borne member of the genus Flavivirus in the Japanese encephalitis virus (JEV) serogroup. USUV was detected in Austria in 2001 causing a high mortality rate in blackbirds; the reference strain (SAAR-1776) was isolated in 1958 from mosquitoes in South Africa and has never been associated with avian mortality. The Austrian and South African isolates exhibited 97% nucleotide and 99% amino acid identity. Phylogenetic trees were constructed displaying the genetic relationships of USUV with other members of the genus Flavivirus. When comparing USUV with other JEV serogroup viruses, the closest lineage was Murray Valley encephalitis virus (nt: 73%, aa: 82%) followed by JEV (nt: 71%, aa: 81%) and West Nile virus (nt: 68%, aa: 75%). Comparison of the genomes showed that the conserved structural elements and putative enzyme motifs were homologous in the two USUV strains and the JEV serogroup. The factors that determine the severe clinical symptoms caused by the Austrian USUV strain in Eurasian blackbirds are discussed. We also offer a possible explanation for the origins and dispersal of USUV, JEV, and MVEV out of Africa.

Amino Acid Sequence↗
PubMed2004

Live flavivirus vaccines: reasons for caution.

CONTEXT: Dengue, Japanese encephalitis, tick-borne encephalitis, yellow fever, and West Nile viruses cause substantial morbidity and mortality each year. Modern transportation and the relaxation of mosquito-control measures are largely responsible for the increase of disease caused by flaviviruses. Without effective antiviral drugs, vaccination offers the best chance of decreasing the incidence of these diseases, and live virus vaccines are the most promising and cost effective. However, flaviviruses can recombine, which raises the possibility of recombination between a vaccine strain and wild-type virus resulting in a new virus with potentially undesirable properties. STARTING POINT: Recently, Arunee Sabchareon and colleagues reported up to 90% seroconversion rates in a phase I trial of live-attenuated dengue-virus vaccines in children (Pediatr Infect Dis J 2004; 23: 99-109). Other live flavivirus vaccines have also been tested against dengue, Japanese encephalitis, and West Nile viruses. Thus far, efficacy seems promising. WHERE NEXT: Safety issues with the live flavivirus vaccines need to be recognised and addressed. The theoretical possibility of untoward recombination events can never be entirely dismissed, but steps can be taken to minimise risk. The development of non-live flavivirus vaccines should be encouraged.

Encephalomyelitis, Western Equine↗
PubMed2004

The potential for West Nile virus to establish outside of its natural range: a consideration of potential mosquito vectors in the United Kingdom.

Outbreaks of West Nile virus (WNV) infection have occurred sporadically in Europe, apparently due to the migration of infected birds and the subsequent establishment of a transmission cycle involving culicine and anopheline mosquitoes. Both human and equine species become infected, but are considered as dead end hosts since they play an insignificant role in the maintenance of the cycle. Following the introduction of WNV into the United States in 1999 it is increasingly apparent that the virus has an extraordinary ability to infect a very broad range of arthropod species. Here we consider the potential for British mosquitoes to transmit WNV in the event that it is introduced into the UK.

Animals↗
PubMed2004

Amino acid changes responsible for attenuation of virus neurovirulence in an infectious cDNA clone of the Oshima strain of tick-borne encephalitis virus.

A stable full-length infectious cDNA clone of the Oshima strain of Tick-borne encephalitis virus (Far-Eastern subtype) was developed by a long high-fidelity RT-PCR and one-step cloning procedure. The infectious clone (O-IC) had four amino acid substitutions and produced smaller plaques when compared with the parent Oshima 5-10 strain. Using site-directed mutagenesis, the substitutions were reverted to restore the parent virus sequence (O-IC-pt). Although genetically identical, parent virus Oshima 5-10 and virus recovered from O-IC-pt demonstrated some biological differences that are possibly explained by the presence of quasispecies with differing virulence characteristics within the original virus population. These observations may have implications for vaccines based on modified infectious clones. It was also demonstrated that the amino acid substitution E-S(40)-->P at position 40 in the envelope (E) glycoprotein was responsible for plaque size reduction, reduced infectious virus yields in cell culture and reduced mouse neurovirulence. Additionally, two amino acid substitutions in the non-structural (NS)5 protein (virus RNA-dependent RNA polymerase) NS5-V(378)-->A and NS5-R(674)-->K also contributed to attenuation of virulence in mice, but did not demonstrate a noticeable biological effect in baby hamster kidney cell culture. Comparative neurovirulence tests revealed how the accumulation of individual mutations (E-S(40)-->P, NS5-V(378)-->A and NS5-R(674)-->K) can result in the attenuation of a virus.

Amino Acid Sequence↗
PubMed2003

Origins, evolution, and vector/host coadaptations within the genus Flavivirus.

Although viruses in the genus Flavivirus share complex antigenic interrelationships, they can be divided into four phylogenetic/ecological groups: two mosquito-borne groups, a tick-borne group, and nonvectored viruses. These divisions largely reflect the selective constraints imposed on the viruses by the vertebrate hosts, the invertebrate vectors, and the associated ecologies. Phylogenetic trees based on the flavivirus genetic sequence show characteristic branching patterns that reflect these groupings. This review describes the evolution and possible origins of individual flaviviruses, correlating ecological and epidemiological characteristics with their phylogenies and geographic dispersal. It will also become apparent that many of the phylogenetic lineages that define species diverged relatively recently, and the subsequent dispersal and epidemiology of these viruses have therefore been significantly influenced by increasing human population densities and activities such as recreation, urbanization, land reclamation, transportation, and deforestation. This review also considers some of the likely implications of persistent/chronic infections in relation to virus dispersal and recombination between related flaviviruses on phylogenetic analysis and vaccine development strategies.

Adaptation, Physiological↗
PubMed2003

Tick-borne flaviviruses.

Tick-borne encephalitis (TBE), one of the most dangerous neuroinfections in Europe and Asia, is caused by tick-borne encephalitis virus (TBEV) and currently involves approximately 11,000 human cases annually, mostly in Russia. This chapter describes the main problems associated with the epidemiology, ecology, pathogenesis, and control of this disease. We have attempted to review the factors that influence the incidence and distribution of TBE, and to discuss possible reasons for the different clinical manifestations including most commonly observed asymptomatic infections, fever forms, acute encephalitis, and the less frequently registered biphasic milk fever and chronic encephalitis. Epidemiologic data concerning the other tick-borne flaviviruses, namely Louping ill virus, Langat virus, and Powassan virus that also produce encephalitis on a smaller scale, are also presented. Here we describe the history and current epidemiological role of Omsk hemorrhagic fever virus and Kyasanur forest disease virus, two viruses that are genetically closely related to TBEV, but produce hemorrhagic fever instead of encephalitis, and provide possible explanations for these differences. The other viruses in the tick-borne flavivirus group are also included despite the fact that they do not play an essential epidemiologic role in humans. This chapter contains a brief history of vaccination against TBE including the trials with live attenuated vaccine and reviews the modern trends in development of vaccine virus strains.

Animals↗
PubMed2003

Phylogenetic analysis reveals a low rate of homologous recombination in negative-sense RNA viruses.

Recombination is increasingly seen as an important means of shaping genetic diversity in RNA viruses. However, observed recombination frequencies vary widely among those viruses studied to date, with only sporadic occurrences reported in RNA viruses with negative-sense genomes. To determine the extent of homologous recombination in negative-sense RNA viruses, phylogenetic analyses of 79 gene sequence alignments from 35 negative-sense RNA viruses (a total of 2154 sequences) were carried out. Powerful evidence was found for recombination, in the form of incongruent phylogenetic trees between different gene regions, in only five sequences from Hantaan virus, Mumps virus and Newcastle disease virus. This is the first report of recombination in these viruses. More tentative evidence for recombination, where conflicting phylogenetic trees were observed (but were without strong bootstrap support) and/or where putative recombinant regions were very short, was found in three alignments from La Crosse virus and Puumala virus. Finally, patterns of sequence variation compatible with the action of recombination, but not definitive evidence for this process, were observed in a further ten viruses: Canine distemper virus, Crimean-Congo haemorrhagic fever virus, Influenza A virus, Influenza B virus, Influenza C virus, Lassa virus, Pirital virus, Rabies virus, Rift Valley Fever virus and Vesicular stomatitis virus. The possibility of recombination in these viruses should be investigated further. Overall, this study reveals that rates of homologous recombination in negative-sense RNA viruses are very much lower than those of mutation, with many viruses seemingly clonal on current data. Consequently, recombination rate is unlikely to be a trait that is set by natural selection to create advantageous or purge deleterious mutations.

Animals↗
PubMed2003

Serological evidence of West Nile virus, Usutu virus and Sindbis virus infection of birds in the UK.

The introduction and rapid dispersal of the African flavivirus West Nile virus (WNV) throughout North America, and the high fatality rate due to encephalitis in birds, horses, other wildlife species and humans, has attracted major attention worldwide. Usutu virus, another flavivirus, came to prominence in 2001, when it was identified as the agent responsible for a drop in the bird population in Austria; previously this encephalitic virus was found only in birds and mosquitoes in Africa. Sindbis virus, a pathogenic alphavirus that causes arthritis, is widespread throughout Africa, Europe, Asia and Australia, infecting a range of arthropods and vertebrates and is genetically related to encephalitic viruses in North America. Currently there is no evidence that any of these viruses cause disease in the UK. Here the presence of virus-specific neutralizing antibodies is reported in the sera of resident and migrant birds in the UK, implying that each of these viruses is being introduced to UK birds, possibly by mosquitoes. This is supported by nucleotide sequencing that identified three slightly different sequences of WNV RNA in tissues of magpies and a blackbird. The detection of specific neutralizing antibodies to WNV in birds provides a plausible explanation for the lack of evidence of a decrease in the bird population in the UK compared with North America. The potential health risk posed to humans and animals by these viruses circulating in the UK is discussed.

Alphavirus Infections↗
PubMed2002

Phylogenetic relationships and differential selection pressures among genotypes of dengue-2 virus.

To elucidate the processes controlling the emergence and spread of dengue-2 virus (DEN-2) we examined the evolution of viral isolates sampled from both local (Viet Nam) and global populations. Our phylogenetic analysis, incorporating envelope (E) glycoprotein sequences from 147 isolates of DEN-2, provided a more complete picture of viral diversity, with a newly defined "Cosmopolitan" genotype having a near global distribution and two other genotypes restricted to Asia. By analyzing rates of synonymous and nonsynonymous substitution we determined that genotypes have experienced different selection pressures, with some evidence of positive selection in the Cosmopolitan genotype and one of the two Asian genotypes, but that the transition from sylvatic to human transmission was not accompanied by adaptive evolution of the E gene. Although there was no association between selection pressures acting on the E gene and proposed virulence differences among genotypes, some putatively selected amino acid sites have previously been implicated in changing viral pathogenicity, most notably E-390, and may also affect transmittability. These findings have implications for the future spread of DEN-2.

Africa↗
PubMed2001

Phylogenetic relationships of flaviviruses correlate with their epidemiology, disease association and biogeography.

Phylogenetic analysis of the Flavivirus genus, using either partial sequences of the non-structural 5 gene or the structural envelope gene, revealed an extensive series of clades defined by their epidemiology and disease associations. These phylogenies identified mosquito-borne, tick-borne and no-known-vector (NKV) virus clades, which could be further subdivided into clades defined by their principal vertebrate host. The mosquito-borne flaviviruses revealed two distinct epidemiological groups: (i) the neurotropic viruses, often associated with encephalitic disease in humans or livestock, correlated with the Culex species vector and bird reservoirs and (ii) the non-neurotropic viruses, associated with haemorrhagic disease in humans, correlated with the Aedes species vector and primate hosts. Thus, the tree topology describing the virus-host association may reflect differences in the feeding behaviour between Aedes and Culex mosquitoes. The tick-borne viruses also formed two distinct groups: one group associated with seabirds and the other, the tick-borne encephalitis complex viruses, associated primarily with rodents. The NKV flaviviruses formed three distinct groups: one group, which was closely related to the mosquito-borne viruses, associated with bats; a second group, which was more genetically distant, also associated with bats; and a third group associated with rodents. Each epidemiological group within the phylogenies revealed distinct geographical clusters in either the Old World or the New World, which for mosquito-borne viruses may reflect an Old World origin. The correlation between epidemiology, disease correlation and biogeography begins to define the complex evolutionary relationships between the virus, vector, vertebrate host and ecological niche.

Aedes↗