The Experts below are selected from a list of 10893 Experts worldwide ranked by ideXlab platform
Michael R Holbrook - One of the best experts on this subject based on the ideXlab platform.
-
historical perspectives on flavivirus research
2017Co-Authors: Michael R HolbrookAbstract:The Flaviviruses are small single-stranded RNA viruses that are typically transmitted by mosquito or tick vectors. These “arboviruses” are found around the world and account for a significant number of cases of human disease. The Flaviviruses cause diseases ranging from mild or sub-clinical infections to lethal hemorrhagic fever or encephalitis. In many cases, survivors of neurologic flavivirus infections suffer long-term debilitating sequelae. Much like the emergence of West Nile virus in the United States in 1999, the recent emergence of Zika virus in the Americas has significantly increased the awareness of mosquito-borne viruses. The diseases caused by several Flaviviruses have been recognized for decades, if not centuries. However, there is still a lot that is unknown about the Flaviviruses as the recent experience with Zika virus has taught us. The objective of this review is to provide a general overview and some historical perspective on several Flaviviruses that cause significant human disease. In addition, available medical countermeasures and significant gaps in our understanding of flavivirus biology are also discussed.
-
Advances in Flavivirus Research
2017Co-Authors: Michael R HolbrookAbstract:The Flaviviruses are composed almost entirely of arthropod-borne viruses, a subset of which are responsible for millions of cases of human disease each year. Among these viruses are dengue virus—a scourge throughout the tropical regions of Asia and the Americas; yellow fever virus—the “original” hemorrhagic fever virus; and the recently emerged Zika virus. While the Flaviviruses are related genetically, in their structure and in their replication processes, the dissimilarity of diseases caused by the Flaviviruses is remarkable. In this Special Issue, primary research articles and reviews discuss topics ranging from broadly applicable questions of nuclear translocation of viral proteins to virus-specific envelope protein epitopes that may be associated with virus attenuation. Also included in this issue are articles discussing findings with less well known Flaviviruses including pegivirus and Duck Tembusu virus. The latter provides a reminder that the Flaviviruses not only impact humans, but other species as well
-
structure of the envelope protein domain iii of omsk hemorrhagic fever virus
2006Co-Authors: David E Volk, Leonard Chavez, Michael R Holbrook, David W. C. Beasley, Alan D T Barrett, David G. GorensteinAbstract:We have solved the NMR solution structure of domain III from the Omsk hemorrhagic fever virus envelope protein and report the first sequencing of the Guriev strain of this virus. Important structural differences between tick-borne Flaviviruses, such as OHFV and TBE, and mosquito-borne Flaviviruses, such as West Nile virus, are discussed.
-
analysis of the complete genome of the tick borne flavivirus omsk hemorrhagic fever virus
2003Co-Authors: Li Li, Daryl Dick, Robert E Shope, Heinz Feldmann, Alan D T Barrett, Michael R HolbrookAbstract:Abstract Omsk hemorrhagic fever virus (OHF) is a tick-borne flavivirus endemic to Western Siberia. This virus is the only known tick-borne flavivirus to cause hemorrhagic disease in humans in the absence of encephalitis. OHF virus circulates within a small, defined niche in which other tick-borne complex Flaviviruses are also present. The objectives of this study were to genetically classify OHF virus based on its complete genome and to identify genetic determinants that might be involved in tissue tropism and viral replication leading to the disease state caused by this virus. The OHF virus genome was sequenced and phylogenetic analysis demonstrated that OHF virus falls within the tick-borne encephalitis serocomplex of Flaviviruses, yet is distinct from other members of the complex, including those closely associated geographically. OHF is also distinct from Alkhurma (ALK) and Kyasanur forest disease (KFD) viruses, both of which cause disease that includes hemorrhagic and encephalitic manifestations. Several amino acid residues were found to be distinct among OHF, KFD, and ALK viruses; these residues include E-76, which is closely associated with the viral envelope protein fusion peptide. In addition, variation between the viral 5′-untranslated region of OHF and other tick-borne Flaviviruses suggests potential variability in viral replication. These data demonstrate that OHF is a unique virus among the tick-borne Flaviviruses and also provide insight to viral biodiversity and tropism.
-
biophysical characterization and vector specific antagonist activity of domain iii of the tick borne flavivirus envelope protein
2001Co-Authors: S Bhardwaj, Michael R Holbrook, Robert E Shope, Alan D T Barrett, Stanley J WatowichAbstract:The molecular determinants responsible for flavivirus host cell binding and tissue tropism are largely unknown, although domain III of the envelope protein has been implicated in these functions. We examined the solution properties and antagonist activity of Langat virus domain III. Our results suggest that domain III adopts a stably folded structure that can mediate binding of tick-borne Flaviviruses but not mosquito-borne Flaviviruses to their target cells. Three clusters of phylogenetically conserved residues are identified that may be responsible for the vector-specific antagonist activity of domain III.
Ernest A. Gould - One of the best experts on this subject based on the ideXlab platform.
-
New Insights into Flavivirus Evolution, Taxonomy and Biogeographic History, Extended by Analysis of Canonical and Alternative Coding Sequences
2015Co-Authors: Gregory Moureau, Ernest A. Gould, Andrew E Firth, Shelley Cook, Philippe Lemey, Antoine Nougairede, Naomi L. Forrester, Maxim Khasnatinov, Remi N. Charrel, Xavier De LamballerieAbstract:To generate the most diverse phylogenetic dataset for the Flaviviruses to date, we determined the genomic sequences and phylogenetic relationships of 14 Flaviviruses, of which 10 are primarily associated with Culex spp. mosquitoes. We analyze these data, in conjunction with a comprehensive collection of flavivirus genomes, to characterize flavivirus evolutionary and biogeographic history in unprecedented detail and breadth. Based on the presumed introduction of yellow fever virus into the Americas via the transatlantic slave trade, we extrapolated a timescale for a relevant subset of Flaviviruses whose evolutionary history, shows that different Culex-spp. associated Flaviviruses have been introduced from the Old World to the New World on at least five separate occasions, with 2 different sets of factors likely to have contributed to the dispersal of the different viruses. We also discuss the significance of programmed ribosomal frameshifting in a central region of the polypro-tein open reading frame in some mosquito-associated Flaviviruses.
-
molecular evolution of the insect specific Flaviviruses
2012Co-Authors: Shelley Cook, Ernest A. Gould, Edward C Holmes, Gregory Moureau, Andrew Kitchen, Xavier De Lamballerie, Ralph E HarbachAbstract:There has been an explosion in the discovery of ‘insect-specific’ Flaviviruses and/or their related sequences in natural mosquito populations. Herein we review all ‘insect-specific’ flavivirus sequences currently available and conduct phylogenetic analyses of both the ‘insect-specific’ Flaviviruses and available sequences of the entire genus Flavivirus. We show that there is no statistical support for virus–mosquito co-divergence, suggesting that the ‘insect-specific’ Flaviviruses may have undergone multiple introductions with frequent host switching. We discuss potential implications for the evolution of vectoring within the family Flaviviridae. We also provide preliminary evidence for potential recombination events in the history of cell fusing agent virus. Finally, we consider priorities and guidelines for future research on ‘insect-specific’ Flaviviruses, including the vast potential that exists for the study of biodiversity within a range of potential hosts and vectors, and its effect on the emergence and maintenance of the Flaviviruses.
-
Tick-borne Flaviviruses.
2003Co-Authors: T.s. Gritsun, Patricia A. Nuttall, Ernest A. GouldAbstract: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.
-
phylogeny of the genus flavivirus using complete coding sequences of arthropod borne viruses and viruses with no known vector
2000Co-Authors: Frederique Billoir, Ernest A. Gould, Reine De Chesse, Hugues Tolou, Philippe De Micco, Xavier De LamballerieAbstract:Attempts to define the evolutionary relationships and origins of viruses in the genus Flavivirus are hampered by the lack of genetic information particularly amongst the non-vectored Flaviviruses. Using a novel protocol for sequence determination, the first complete coding sequence of St Louis encephalitis virus and those of two representative non-vectored Flaviviruses, Rio Bravo (isolated from bat) and Apoi (isolated from rodent), are reported. The encoded polyproteins of Rio Bravo and Apoi virus are the smallest described to date within the genus Flavivirus. The highest similarities with other Flaviviruses were found in the NS3 and NS5 genes. The proteolytic cleavage sites for the viral serine protease were highly conserved among the Flaviviruses completely sequenced to date. Comparative genetic amino acid alignments revealed that p-distance cut-off values of 0·330–0·470 distinguished the arthropod-borne viruses according to their recognized serogroups and Rio Bravo and Apoi virus were assigned to two distinct non-vectored virus groups. Within these serogroups, cladogenesis based on the complete ORF sequence was similar to trees based on envelope and NS5 sequences. In contrast, branching patterns at the deeper nodes of the tree were different from those reported in the previous study of NS5 sequences. The significance of these observations is discussed.
-
secondary structure of the 3 untranslated region of Flaviviruses similarities and differences
1997Co-Authors: Vitali Proutski, Ernest A. Gould, Edward C HolmesAbstract:Genetic algorithm-based RNA secondary structure prediction was used in combination with comparative sequence analysis to construct models of folding for the distal part of the 3'-untranslated region of Flaviviruses belonging to four serological groups. Elements of RNA secondary structure that are preserved among all the Flaviviruses studied were revealed, despite the high degree of sequence divergence between them. At the same time, structural elements were observed that distinguish members of different serological groups and, in particular, a region of remarkable structural divergence between the tick-borne and mosquito-borne Flaviviruses was found. Application of the genetic algorithm also revealed that the 3'-terminus of flaviviral genomic RNA may take on alternative conformations, which are not observed in the 3'-terminus of complementary minus strand RNA. These alternative folding patterns may have roles in the regulation of transcription and translation initiation and in the switch between them.
Edward C Holmes - One of the best experts on this subject based on the ideXlab platform.
-
molecular evolution of the insect specific Flaviviruses
2012Co-Authors: Shelley Cook, Ernest A. Gould, Edward C Holmes, Gregory Moureau, Andrew Kitchen, Xavier De Lamballerie, Ralph E HarbachAbstract:There has been an explosion in the discovery of ‘insect-specific’ Flaviviruses and/or their related sequences in natural mosquito populations. Herein we review all ‘insect-specific’ flavivirus sequences currently available and conduct phylogenetic analyses of both the ‘insect-specific’ Flaviviruses and available sequences of the entire genus Flavivirus. We show that there is no statistical support for virus–mosquito co-divergence, suggesting that the ‘insect-specific’ Flaviviruses may have undergone multiple introductions with frequent host switching. We discuss potential implications for the evolution of vectoring within the family Flaviviridae. We also provide preliminary evidence for potential recombination events in the history of cell fusing agent virus. Finally, we consider priorities and guidelines for future research on ‘insect-specific’ Flaviviruses, including the vast potential that exists for the study of biodiversity within a range of potential hosts and vectors, and its effect on the emergence and maintenance of the Flaviviruses.
-
a multigene analysis of the phylogenetic relationships among the Flaviviruses family flaviviridae and the evolution of vector transmission
2006Co-Authors: Shelley Cook, Edward C HolmesAbstract:The genus Flavivirus (family Flaviviridae) presently comprises around 70 single-strand positive-sense RNA viruses. These replicate in a range of vertebrate and invertebrate cells and may be mosquito-borne, tick-borne or have no-known-vector. Since transmission mode correlates strongly with phylogeny, the Flaviviruses constitute a valuable model for the evolution of vector-borne disease. Attempts to resolve the higher-level taxonomic relationships of the Flaviviruses through molecular phylogenetics have thus far proved inconclusive because of conflicting positions for the three main transmission groups. We conducted the most comprehensive phylogenetic study to date, involving maximum likelihood analyses of the NS3 and NS5 genes and the entire genome sequences available at present. For the first time, we use and test a variety of more robust methods of sequence alignment and appropriate models of amino acid replacement to study these highly divergent sequences, and explicitly test specific hypotheses of tree topology. We show that (i) the NS5 gene contains insufficient phylogenetic signal to choose between competing topological hypotheses, (ii) the NS3 gene and whole genome data indicate that the mosquito-borne Flaviviruses represent an outgroup to the remaining Flaviviruses, and (iii) that tick-borne transmission is probably a derived trait within the genus.
-
secondary structure of the 3 untranslated region of Flaviviruses similarities and differences
1997Co-Authors: Vitali Proutski, Ernest A. Gould, Edward C HolmesAbstract:Genetic algorithm-based RNA secondary structure prediction was used in combination with comparative sequence analysis to construct models of folding for the distal part of the 3'-untranslated region of Flaviviruses belonging to four serological groups. Elements of RNA secondary structure that are preserved among all the Flaviviruses studied were revealed, despite the high degree of sequence divergence between them. At the same time, structural elements were observed that distinguish members of different serological groups and, in particular, a region of remarkable structural divergence between the tick-borne and mosquito-borne Flaviviruses was found. Application of the genetic algorithm also revealed that the 3'-terminus of flaviviral genomic RNA may take on alternative conformations, which are not observed in the 3'-terminus of complementary minus strand RNA. These alternative folding patterns may have roles in the regulation of transcription and translation initiation and in the switch between them.
Alan D T Barrett - One of the best experts on this subject based on the ideXlab platform.
-
structure of the envelope protein domain iii of omsk hemorrhagic fever virus
2006Co-Authors: David E Volk, Leonard Chavez, Michael R Holbrook, David W. C. Beasley, Alan D T Barrett, David G. GorensteinAbstract:We have solved the NMR solution structure of domain III from the Omsk hemorrhagic fever virus envelope protein and report the first sequencing of the Guriev strain of this virus. Important structural differences between tick-borne Flaviviruses, such as OHFV and TBE, and mosquito-borne Flaviviruses, such as West Nile virus, are discussed.
-
analysis of the complete genome of the tick borne flavivirus omsk hemorrhagic fever virus
2003Co-Authors: Li Li, Daryl Dick, Robert E Shope, Heinz Feldmann, Alan D T Barrett, Michael R HolbrookAbstract:Abstract Omsk hemorrhagic fever virus (OHF) is a tick-borne flavivirus endemic to Western Siberia. This virus is the only known tick-borne flavivirus to cause hemorrhagic disease in humans in the absence of encephalitis. OHF virus circulates within a small, defined niche in which other tick-borne complex Flaviviruses are also present. The objectives of this study were to genetically classify OHF virus based on its complete genome and to identify genetic determinants that might be involved in tissue tropism and viral replication leading to the disease state caused by this virus. The OHF virus genome was sequenced and phylogenetic analysis demonstrated that OHF virus falls within the tick-borne encephalitis serocomplex of Flaviviruses, yet is distinct from other members of the complex, including those closely associated geographically. OHF is also distinct from Alkhurma (ALK) and Kyasanur forest disease (KFD) viruses, both of which cause disease that includes hemorrhagic and encephalitic manifestations. Several amino acid residues were found to be distinct among OHF, KFD, and ALK viruses; these residues include E-76, which is closely associated with the viral envelope protein fusion peptide. In addition, variation between the viral 5′-untranslated region of OHF and other tick-borne Flaviviruses suggests potential variability in viral replication. These data demonstrate that OHF is a unique virus among the tick-borne Flaviviruses and also provide insight to viral biodiversity and tropism.
-
biophysical characterization and vector specific antagonist activity of domain iii of the tick borne flavivirus envelope protein
2001Co-Authors: S Bhardwaj, Michael R Holbrook, Robert E Shope, Alan D T Barrett, Stanley J WatowichAbstract:The molecular determinants responsible for flavivirus host cell binding and tissue tropism are largely unknown, although domain III of the envelope protein has been implicated in these functions. We examined the solution properties and antagonist activity of Langat virus domain III. Our results suggest that domain III adopts a stably folded structure that can mediate binding of tick-borne Flaviviruses but not mosquito-borne Flaviviruses to their target cells. Three clusters of phylogenetically conserved residues are identified that may be responsible for the vector-specific antagonist activity of domain III.
Shelley Cook - One of the best experts on this subject based on the ideXlab platform.
-
New Insights into Flavivirus Evolution, Taxonomy and Biogeographic History, Extended by Analysis of Canonical and Alternative Coding Sequences
2015Co-Authors: Gregory Moureau, Ernest A. Gould, Andrew E Firth, Shelley Cook, Philippe Lemey, Antoine Nougairede, Naomi L. Forrester, Maxim Khasnatinov, Remi N. Charrel, Xavier De LamballerieAbstract:To generate the most diverse phylogenetic dataset for the Flaviviruses to date, we determined the genomic sequences and phylogenetic relationships of 14 Flaviviruses, of which 10 are primarily associated with Culex spp. mosquitoes. We analyze these data, in conjunction with a comprehensive collection of flavivirus genomes, to characterize flavivirus evolutionary and biogeographic history in unprecedented detail and breadth. Based on the presumed introduction of yellow fever virus into the Americas via the transatlantic slave trade, we extrapolated a timescale for a relevant subset of Flaviviruses whose evolutionary history, shows that different Culex-spp. associated Flaviviruses have been introduced from the Old World to the New World on at least five separate occasions, with 2 different sets of factors likely to have contributed to the dispersal of the different viruses. We also discuss the significance of programmed ribosomal frameshifting in a central region of the polypro-tein open reading frame in some mosquito-associated Flaviviruses.
-
novel Flaviviruses from mosquitoes mosquito specific evolutionary lineages within the phylogenetic group of mosquito borne Flaviviruses
2014Co-Authors: Eili Huhtamo, Shelley Cook, Gregory Moureau, Ralph E Harbach, Niina Putkuri, Satu Kurkela, Nathalie Y Uzcategui, Tarja Sironen, Suvi Kuivanen, Andrew E FirthAbstract:Novel Flaviviruses that are genetically related to pathogenic mosquito-borne Flaviviruses (MBFV) have been isolated from mosquitoes in various geographical locations, including Finland. We isolated and characterized another novel virus of this group from Finnish mosquitoes collected in 2007, designated as Ilomantsi virus (ILOV). Unlike the MBFV that infect both vertebrates and mosquitoes, the MBFV-related viruses appear to be specific to mosquitoes similar to the insect-specific Flaviviruses (ISFs). In this overview of MBFV-related viruses we conclude that they differ from the ISFs genetically and antigenically. Phylogenetic analyses separated the MBFV-related viruses isolated in Africa, the Middle East and South America from those isolated in Europe and Asia. Serological cross-reactions of MBFV-related viruses with other Flaviviruses and their potential for vector-borne transmission require further characterization. The divergent MBFV-related viruses are probably significantly under sampled to date and provide new information on the variety, properties and evolution of vector-borne Flaviviruses.
-
molecular evolution of the insect specific Flaviviruses
2012Co-Authors: Shelley Cook, Ernest A. Gould, Edward C Holmes, Gregory Moureau, Andrew Kitchen, Xavier De Lamballerie, Ralph E HarbachAbstract:There has been an explosion in the discovery of ‘insect-specific’ Flaviviruses and/or their related sequences in natural mosquito populations. Herein we review all ‘insect-specific’ flavivirus sequences currently available and conduct phylogenetic analyses of both the ‘insect-specific’ Flaviviruses and available sequences of the entire genus Flavivirus. We show that there is no statistical support for virus–mosquito co-divergence, suggesting that the ‘insect-specific’ Flaviviruses may have undergone multiple introductions with frequent host switching. We discuss potential implications for the evolution of vectoring within the family Flaviviridae. We also provide preliminary evidence for potential recombination events in the history of cell fusing agent virus. Finally, we consider priorities and guidelines for future research on ‘insect-specific’ Flaviviruses, including the vast potential that exists for the study of biodiversity within a range of potential hosts and vectors, and its effect on the emergence and maintenance of the Flaviviruses.
-
a multigene analysis of the phylogenetic relationships among the Flaviviruses family flaviviridae and the evolution of vector transmission
2006Co-Authors: Shelley Cook, Edward C HolmesAbstract:The genus Flavivirus (family Flaviviridae) presently comprises around 70 single-strand positive-sense RNA viruses. These replicate in a range of vertebrate and invertebrate cells and may be mosquito-borne, tick-borne or have no-known-vector. Since transmission mode correlates strongly with phylogeny, the Flaviviruses constitute a valuable model for the evolution of vector-borne disease. Attempts to resolve the higher-level taxonomic relationships of the Flaviviruses through molecular phylogenetics have thus far proved inconclusive because of conflicting positions for the three main transmission groups. We conducted the most comprehensive phylogenetic study to date, involving maximum likelihood analyses of the NS3 and NS5 genes and the entire genome sequences available at present. For the first time, we use and test a variety of more robust methods of sequence alignment and appropriate models of amino acid replacement to study these highly divergent sequences, and explicitly test specific hypotheses of tree topology. We show that (i) the NS5 gene contains insufficient phylogenetic signal to choose between competing topological hypotheses, (ii) the NS3 gene and whole genome data indicate that the mosquito-borne Flaviviruses represent an outgroup to the remaining Flaviviruses, and (iii) that tick-borne transmission is probably a derived trait within the genus.