The Experts below are selected from a list of 270 Experts worldwide ranked by ideXlab platform
Stefan Rothenburg - One of the best experts on this subject based on the ideXlab platform.
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poxviruses and the evolution of Host Range and virulence
Infection Genetics and Evolution, 2014Co-Authors: Sherry L Haller, Grant Mcfadden, Chen Peng, Stefan RothenburgAbstract:Poxviruses as a group can infect a large number of animals. However, at the level of individual viruses, even closely related poxviruses display highly diverse Host Ranges and virulence. For example, variola virus, the causative agent of smallpox, is human-specific and highly virulent only to humans, whereas related cowpox viruses naturally infect a broad spectrum of animals and only cause relatively mild disease in humans. The successful replication of poxviruses depends on their effective manipulation of the Host antiviral responses, at the cellular-, tissue- and species-specific levels, which constitutes a molecular basis for differences in poxvirus Host Range and virulence. A number of poxvirus genes have been identified that possess Host Range function in experimental settings, and many of these Host Range genes target specific antiviral Host pathways. Herein, we review the biology of poxviruses with a focus on Host Range, zoonotic infections, virulence, genomics and Host Range genes as well as the current knowledge about the function of poxvirus Host Range factors and how their interaction with the Host innate immune system contributes to poxvirus Host Range and virulence. We further discuss the evolution of Host Range and virulence in poxviruses as well as Host switches and potential poxvirus threats for human and animal health.
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A survey of Host Range genes in poxvirus genomes
Infection Genetics and Evolution, 2012Co-Authors: Kirsten A. Bratke, Aoife Mclysaght, Stefan RothenburgAbstract:Poxviruses are widespread pathogens, which display extremely different Host Ranges. Whereas some pox- viruses, including variola virus, display narrow Host Ranges, others such as cowpox viruses naturally infect a wide Range of mammals. The molecular basis for differences in Host Range are poorly understood but apparently depend on the successful manipulation of the Host antiviral response. Some poxvirus genes have been shown to confer Host tropism in experimental settings and are thus called Host Range factors. Identified Host Range genes include vaccinia virus K1L, K3L, E3L, B5R, C7L and SPI-1, cowpox virus CP77/CHOhr, ectromelia virus p28 and 022, and myxoma virus T2, T4, T5, 11L, 13L, 062R and 063R. These genes encode for ankyrin repeat-containing proteins, tumor necrosis factor receptor II homologs, apop- tosis inhibitor T4-related proteins, Bcl-2-related proteins, pyrin domain-containing proteins, cellular ser- ine protease inhibitors (serpins), short complement-like repeats containing proteins, KilA-N/RING domain-containing proteins, as well as inhibitors of the double-stranded RNA-activated protein kinase PKR. We conducted a systematic survey for the presence of known Host Range genes and closely related family members in poxvirus genomes, classified them into subgroups based on their phylogenetic rela- tionship and correlated their presence with the poxvirus phylogeny. Common themes in the evolution of poxvirus Host Range genes are lineage-specific duplications and multiple independent inactivation events. Our analyses yield new insights into the evolution of poxvirus Host Range genes. Implications of our findings for poxvirus Host Range and virulence are discussed.
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The poxvirus C7L Host Range factor superfamily.
Current Opinion in Virology, 2012Co-Authors: Stefan Rothenburg, Grant McfaddenAbstract:Host Range factors, expressed by the poxvirus family, determine the Host tropism of species, tissue, and cell specificity. C7L family members exist in the genomes of most sequenced mammalian poxviruses, suggesting an evolutionarily conserved effort adapting to the Hosts. In general, C7L orthologs influence the Host tropism in mammalian cell culture, and for some poxviruses it is essential for the complete viral life cycle in vitro and in vivo. The C7L family members lack obvious sequence homology with any other known viral or cellular proteins. Here we review recent findings from an evolutionary perspective and summarize recent progress that broadens our view on the role of C7L family members in mediating poxvirus Host Range and antagonizing the Host defense system.
José Miguel Ponciano - One of the best experts on this subject based on the ideXlab platform.
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evolutionary paths that expand plasmid Host Range implications for spread of antibiotic resistance
Molecular Biology and Evolution, 2016Co-Authors: Wesley Loftieeaton, Hirokazu Yano, Stephen Burleigh, Ryan S Simmons, Julie M Hughes, Linda M Rogers, Samuel S Hunter, Matthew L Settles, Larry J Forney, José Miguel PoncianoAbstract:: The World Health Organization has declared the emergence of antibiotic resistance to be a global threat to human health. Broad-Host-Range plasmids have a key role in causing this health crisis because they transfer multiple resistance genes to a wide Range of bacteria. To limit the spread of antibiotic resistance, we need to gain insight into the mechanisms by which the Host Range of plasmids evolves. Although initially unstable plasmids have been shown to improve their persistence through evolution of the plasmid, the Host, or both, the means by which this occurs are poorly understood. Here, we sought to identify the underlying genetic basis of expanded plasmid Host-Range and increased persistence of an antibiotic resistance plasmid using a combined experimental-modeling approach that included whole-genome resequencing, molecular genetics and a plasmid population dynamics model. In nine of the ten previously evolved clones, changes in Host and plasmid each slightly improved plasmid persistence, but their combination resulted in a much larger improvement, which indicated positive epistasis. The only genetic change in the plasmid was the acquisition of a transposable element from a plasmid native to the Pseudomonas Host used in these studies. The analysis of genetic deletions showed that the critical genes on this transposon encode a putative toxin-antitoxin (TA) and a cointegrate resolution system. As evolved plasmids were able to persist longer in multiple naive Hosts, acquisition of this transposon also expanded the plasmid's Host Range, which has important implications for the spread of antibiotic resistance.
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Adaptive Plasmid Evolution Results in Host-Range Expansion of a Broad-Host-Range Plasmid
Genetics, 2008Co-Authors: Leen De Gelder, Julia Williams, José Miguel Ponciano, Masahiro SotaAbstract:Little is known about the Range of Hosts in which broad-Host-Range (BHR) plasmids can persist in the absence of selection for plasmid-encoded traits, and whether this “long-term Host Range” can evolve over time. Previously, the BHR multidrug resistance plasmid pB10 was shown to be highly unstable in Stenotrophomonas maltophilia P21 and Pseudomonas putida H2. To investigate whether this plasmid can adapt to such unfavorable Hosts, we performed evolution experiments wherein pB10 was maintained in strain P21, strain H2, and alternatingly in P21 and H2. Plasmids that evolved in P21 and in both Hosts showed increased stability and decreased cost in ancestral Host P21. However, the latter group showed higher variability in stability patterns, suggesting that regular switching between distinct Hosts hampered adaptive plasmid evolution. The plasmids evolved in P21 were also equally or more stable in other Hosts compared to pB10, which suggested true Host-Range expansion. The complete genome sequences of four evolved plasmids with improved stability showed only one or two genetic changes. The stability of plasmids evolved in H2 improved only in their coevolved Hosts, not in the ancestral Host. Thus a BHR plasmid can adapt to an unfavorable Host and thereby expand its long-term Host Range.
Grant Mcfadden - One of the best experts on this subject based on the ideXlab platform.
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Chapter 3 Poxvirus Host Range Genes
Advances in Virus Research, 2020Co-Authors: Steven J. Werden, Masmudur M. Rahman, Grant McfaddenAbstract:As a family of viruses, poxviruses collectively exhibit a broad Host Range and most of the individual members are capable of replicating in a wide array of cell types from various Host species, at least in vitro. At the cellular level, poxvirus tropism is dependent not upon specific cell surface receptors, but rather upon: (1) the ability of the cell to provide intracellular complementing factors needed for productive virus replication, and (2) the ability of the specific virus to successfully manipulate intracellular signaling networks that regulate cellular antiviral processes downstream of virus entry. The large genomic coding capacity of poxviruses enables the virus to express a unique collection of viral proteins that function as Host Range factors, which specifically target and manipulate Host signaling pathways to establish optimal cellular conditions for viral replication. Functionally, the known Host Range factors from poxviruses have been associated with manipulation of a diverse array of cellular targets, which includes cellular kinases and phosphatases, apoptosis, and various antiviral pathways. To date, only a small number of poxvirus Host Range genes have been identified and studied, and only a handful of these have been functionally characterized. For this reason, poxvirus Host Range factors represent a potential gold mine for the discovery of novel pathogen–Host protein interactions. This review summarizes our current understanding of the mechanisms by which the known poxvirus Host Range genes, and their encoded factors, expand tropism through the manipulation of Host cell intracellular signaling pathways.
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poxviruses and the evolution of Host Range and virulence
Infection Genetics and Evolution, 2014Co-Authors: Sherry L Haller, Grant Mcfadden, Chen Peng, Stefan RothenburgAbstract:Poxviruses as a group can infect a large number of animals. However, at the level of individual viruses, even closely related poxviruses display highly diverse Host Ranges and virulence. For example, variola virus, the causative agent of smallpox, is human-specific and highly virulent only to humans, whereas related cowpox viruses naturally infect a broad spectrum of animals and only cause relatively mild disease in humans. The successful replication of poxviruses depends on their effective manipulation of the Host antiviral responses, at the cellular-, tissue- and species-specific levels, which constitutes a molecular basis for differences in poxvirus Host Range and virulence. A number of poxvirus genes have been identified that possess Host Range function in experimental settings, and many of these Host Range genes target specific antiviral Host pathways. Herein, we review the biology of poxviruses with a focus on Host Range, zoonotic infections, virulence, genomics and Host Range genes as well as the current knowledge about the function of poxvirus Host Range factors and how their interaction with the Host innate immune system contributes to poxvirus Host Range and virulence. We further discuss the evolution of Host Range and virulence in poxviruses as well as Host switches and potential poxvirus threats for human and animal health.
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The poxvirus C7L Host Range factor superfamily.
Current Opinion in Virology, 2012Co-Authors: Stefan Rothenburg, Grant McfaddenAbstract:Host Range factors, expressed by the poxvirus family, determine the Host tropism of species, tissue, and cell specificity. C7L family members exist in the genomes of most sequenced mammalian poxviruses, suggesting an evolutionarily conserved effort adapting to the Hosts. In general, C7L orthologs influence the Host tropism in mammalian cell culture, and for some poxviruses it is essential for the complete viral life cycle in vitro and in vivo. The C7L family members lack obvious sequence homology with any other known viral or cellular proteins. Here we review recent findings from an evolutionary perspective and summarize recent progress that broadens our view on the role of C7L family members in mediating poxvirus Host Range and antagonizing the Host defense system.
Wesley Loftieeaton - One of the best experts on this subject based on the ideXlab platform.
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evolutionary paths that expand plasmid Host Range implications for spread of antibiotic resistance
Molecular Biology and Evolution, 2016Co-Authors: Wesley Loftieeaton, Hirokazu Yano, Stephen Burleigh, Ryan S Simmons, Julie M Hughes, Linda M Rogers, Samuel S Hunter, Matthew L Settles, Larry J Forney, José Miguel PoncianoAbstract:: The World Health Organization has declared the emergence of antibiotic resistance to be a global threat to human health. Broad-Host-Range plasmids have a key role in causing this health crisis because they transfer multiple resistance genes to a wide Range of bacteria. To limit the spread of antibiotic resistance, we need to gain insight into the mechanisms by which the Host Range of plasmids evolves. Although initially unstable plasmids have been shown to improve their persistence through evolution of the plasmid, the Host, or both, the means by which this occurs are poorly understood. Here, we sought to identify the underlying genetic basis of expanded plasmid Host-Range and increased persistence of an antibiotic resistance plasmid using a combined experimental-modeling approach that included whole-genome resequencing, molecular genetics and a plasmid population dynamics model. In nine of the ten previously evolved clones, changes in Host and plasmid each slightly improved plasmid persistence, but their combination resulted in a much larger improvement, which indicated positive epistasis. The only genetic change in the plasmid was the acquisition of a transposable element from a plasmid native to the Pseudomonas Host used in these studies. The analysis of genetic deletions showed that the critical genes on this transposon encode a putative toxin-antitoxin (TA) and a cointegrate resolution system. As evolved plasmids were able to persist longer in multiple naive Hosts, acquisition of this transposon also expanded the plasmid's Host Range, which has important implications for the spread of antibiotic resistance.
Sherry L Haller - One of the best experts on this subject based on the ideXlab platform.
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poxviruses and the evolution of Host Range and virulence
Infection Genetics and Evolution, 2014Co-Authors: Sherry L Haller, Grant Mcfadden, Chen Peng, Stefan RothenburgAbstract:Poxviruses as a group can infect a large number of animals. However, at the level of individual viruses, even closely related poxviruses display highly diverse Host Ranges and virulence. For example, variola virus, the causative agent of smallpox, is human-specific and highly virulent only to humans, whereas related cowpox viruses naturally infect a broad spectrum of animals and only cause relatively mild disease in humans. The successful replication of poxviruses depends on their effective manipulation of the Host antiviral responses, at the cellular-, tissue- and species-specific levels, which constitutes a molecular basis for differences in poxvirus Host Range and virulence. A number of poxvirus genes have been identified that possess Host Range function in experimental settings, and many of these Host Range genes target specific antiviral Host pathways. Herein, we review the biology of poxviruses with a focus on Host Range, zoonotic infections, virulence, genomics and Host Range genes as well as the current knowledge about the function of poxvirus Host Range factors and how their interaction with the Host innate immune system contributes to poxvirus Host Range and virulence. We further discuss the evolution of Host Range and virulence in poxviruses as well as Host switches and potential poxvirus threats for human and animal health.