scholarly journals A key region of molecular specificity orchestrates unique ephrin-B1 utilization by Cedar virus

2019 ◽  
Vol 3 (1) ◽  
pp. e201900578 ◽  
Author(s):  
Rhys Pryce ◽  
Kristopher Azarm ◽  
Ilona Rissanen ◽  
Karl Harlos ◽  
Thomas A Bowden ◽  
...  

The emergent zoonotic henipaviruses, Hendra, and Nipah are responsible for frequent and fatal disease outbreaks in domestic animals and humans. Specificity of henipavirus attachment glycoproteins (G) for highly species-conserved ephrin ligands underpins their broad host range and is associated with systemic and neurological disease pathologies. Here, we demonstrate that Cedar virus (CedV)—a related henipavirus that is ostensibly nonpathogenic—possesses an idiosyncratic entry receptor repertoire that includes the common henipaviral receptor, ephrin-B2, but, distinct from pathogenic henipaviruses, does not include ephrin-B3. Uniquely among known henipaviruses, CedV can use ephrin-B1 for cellular entry. Structural analyses of CedV-G reveal a key region of molecular specificity that directs ephrin-B1 utilization, while preserving a universal mode of ephrin-B2 recognition. The structural and functional insights presented uncover diversity within the known henipavirus receptor repertoire and suggest that only modest structural changes may be required to modulate receptor specificities within this group of lethal human pathogens.

2019 ◽  
Author(s):  
Rhys Pryce ◽  
Kristopher Azarm ◽  
Ilona Rissanen ◽  
Karl Harlos ◽  
Thomas A. Bowden ◽  
...  

AbstractThe prototypic henipaviruses (HNV), Hendra (HeV) and Nipah (NiV), are emergent zoonotic pathogens responsible for frequent and fatal outbreaks of severe disease in domestic animals and humans. The HNV attachment glycoprotein (G) is a critical determinant of host-species and cell-type tropism. Utilization of highly conserved B-type ephrin ligands as functional entry receptors engenders HNVs with a broad permissive host range, accounts for zoonotic spillover, and is closely aligned with observed disease pathologies. Recent studies have uncovered numerous divergent clades of HNVs globally. Cedar virus (CedV), the closest relative of HeV and NiV identified to date, can establish experimental infections, yet has not been observed to cause overt disease. While the apathogenic phenotype may be attributed to a lack of P-gene derived interferon antagonists, the V and W accessory proteins, additional determinants of differential HNV pathobiology could be involved. Here, through comparative functional and structural analysis of CedV-G, we characterize molecular interactions critical to viral entry. We demonstrate that CedV possesses a unique cellular entry receptor repertoire which, in addition to functional utilization of the common HNV receptor, ephrin-B2, includes the hitherto uncharacterized interaction with ephrin-B1. Crystal structures reveal a conserved recognition mode between diverse HNV-G proteins and their distinct ephrin receptors and identify a region of molecular specificity within CedV-G that is a key determinant of ephrin selectivity. This work provides a platform for understanding the functional diversity and varied receptor tropism characteristics of HNV glycoproteins that will facilitate assessment of the pathogenic potential and transmissibility of newly discovered and uncharacterized HNVs.


2014 ◽  
Author(s):  
◽  
Zhenyu Shen

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Human and animal feces are the main sources of pathogens associated with foodborne and waterborne disease outbreaks. The studies in Volume I proposed ribosomal intervening sequences (IVSs) can be used as host-specific genetic markers for tracking fecal sources in polluted food and water. In Chapter 3, using bioinformatics tools, one IVS in Faecalibacterium 16S rDNA specific to poultry (chicken and turkey) was identified in silico. A PCR assay was then developed to confirm the IVS was only present in fecal or wastewater samples from poultry. The study in Chapter 4 comprehensively examined host specificities of IVSs in 16S rDNA of 73 genera of fecal bacteria. A total of 13 IVSs were identified to be associated particular host sources in silico and the host-specificities of eight of them were confirmed by PCR reactions. Furthermore, a novel beef cattle-specific IVS was identified with next generation sequencing (NGS). Internalization of human pathogens in produce poses high risks to human health because the surface-sanitization method fail to inactivate the pathogens. The study in Volume II proposed to control the pathogen internalization with endophytic Bacillus subtilis strains isolated from vegetables. Twelve endophytic B. subtilis strains isolated from inner tissue of lettuce stems and mung bean seeds displayed inhibitory activity against a Salmonella enterica indicator in vitro and two of them (LCA1 and M24) showed broad inhibitory spectrums. LCA1, M24, and a laboratory strain B. subtilis 168 could internalize in mung bean sprouts and significantly reduced the internalization of S. enterica and enterohaemorrhagic Escherichia coli (EHEC).


2019 ◽  
Vol 5 (1) ◽  
pp. eaau7042 ◽  
Author(s):  
C. D. Harvell ◽  
D. Montecino-Latorre ◽  
J. M. Caldwell ◽  
J. M. Burt ◽  
K. Bosley ◽  
...  

Multihost infectious disease outbreaks have endangered wildlife, causing extinction of frogs and endemic birds, and widespread declines of bats, corals, and abalone. Since 2013, a sea star wasting disease has affected >20 sea star species from Mexico to Alaska. The common, predatory sunflower star (Pycnopodia helianthoides), shown to be highly susceptible to sea star wasting disease, has been extirpated across most of its range. Diver surveys conducted in shallow nearshore waters (n= 10,956; 2006–2017) from California to Alaska and deep offshore (55 to 1280 m) trawl surveys from California to Washington (n= 8968; 2004–2016) reveal 80 to 100% declines across a ~3000-km range. Furthermore, timing of peak declines in nearshore waters coincided with anomalously warm sea surface temperatures. The rapid, widespread decline of this pivotal subtidal predator threatens its persistence and may have large ecosystem-level consequences.


Author(s):  
Eric Richards

Very large numbers of people began to depart the British Isles for the New Worlds after about 1770. This was a pioneering movement, a rehearsal for modern international migration. This book contends that emigration history is not seamless, that it contains large shifts over time and place, and that the modern scale and velocity of mobility have very particular historical roots. The Isle of Man is an ideal starting point in the quest for the engines and mechanisms of emigration, and a particular version of the widespread surge in British emigration in the 1820s. West Sussex was much closer to the centres of the expansionary economy in the new age. North America was the earliest and the greatest theatre of oceanic emigration in which the methods of mass migration were pioneered. Landlocked Shropshire experienced some of the earliest phases of British industrialisation, notably in the Ironbridge/Coalbrookdale district, deep inland on the River Severn. The turmoil in the agrarian and demographic foundations of life reached across the British archipelago. In West Cork and North Tipperary, there was clear evidence of the great structural changes that shook the foundations of these rural societies. The book also discusses the sequences and effects of migration in Wales, Swaledale, Cornwall, Kent, London, and Scottish Highlands. It also deals with Ireland’s place in the more generic context of the origins of migration from the British Isles. The common historical understanding is that the pre-industrial population of the British Isles had been held back by Malthusian checks.


2020 ◽  
pp. 11-32
Author(s):  
Gabriel López-Martínez ◽  
Pilar Espeso-Molinero

En los últimos años, las comunidades europeas de pescadores han sufrido cambios estructurales importantes derivados de las distintas reformas de la Política de Pesca Común (PPC). Los instrumentos aplicados han provocado una transformación en este sector, afectando de manera significativa a las pequeñas poblaciones de pescadores. En este contexto, el estudio antropológico se presenta como una herramienta de gran valor para comprender las respuestas de individuos y comunidades a los nuevos retos. El presente trabajo, basado en información primaria y secundaria recogida en la Región de Murcia en la última década, explora algunas de estas respuestas. Los testimonios de los diferentes informantes muestran el debilitamiento de esta profesión como consecuencia de las herramientas políticas implementadas. La disminución del número de embarcaciones y de trabajadores independientes, unido a la falta de relevo generacional pone en riesgo el conocimiento tradicional de la pesca artesanal. Para reflexionar sobre el presente y el futuro de estas prácticas ancestrales, se exponen una serie de experiencias donde se presenta al pescador como intermediador o agente transmisor de conocimiento, vinculando el legado patrimonial a distintos sectores de la sociedad contemporánea. In recent years, European fishing communities have undergone major structural changes resulting from the different reforms of the Common Fisheries Policy (CFP). The instruments implemented have led to a transformation in this sector, affecting small fishing stocks. In this context, we present an anthropological study as a tool of great value to understand the responses of individuals and communities to new challenges. This work, based on primary and secondary information collected in the last decade in the Region of Murcia (Spain), explores some of these responses. The testimonies of the different informants show the weakening of this profession as a result of the political tools implemented. Decreasing number of boats and self-employed workers, coupled with a lack of generational replacement puts at risk traditional knowledge of artisanal fishing. To reflect on the present and future of these ancestral practices, a series of experiences are presented where the fisherman is revealed as an intermediator or transmitting agent of knowledge, linking the heritage legacy to different sectors of contemporary society.


Author(s):  
Rupert Tipples ◽  
Nona Verwood

The essence of psychological contracting (in the contest of employment) is meeting mutual expectations. The common denominator between legal contracting and psychological contracting is that both are designed to express expectations of the self and of the other. Legal expectations lead to outcomes that are observable, measureable and usually quantifiable. Psychological expectations are usually invisible but nonetheless very real.This paper expresses the need for greater attentions to psychological contracting in a dairy sector going through substantial structural changes involving the replacement of self-employed farmers by hired managers and contract milkers and the widespread adoption of once-a-day milking.


2019 ◽  
Author(s):  
Alyssa Kay Burkhardt ◽  
Kevin L. Childs ◽  
Jie Wang ◽  
Marina L. Ramon ◽  
Frank N. Martin

Abstract Background: Macrophomina phaseolina is a fungal plant pathogen with a broad host range, but one genotype was shown to exhibit host preference/specificity on strawberry. This pathogen lacked a high-quality genome assembly and annotation, and little was known about genomic differences among isolates from different hosts. Results: We used PacBio sequencing and Hi-C scaffolding to provide nearly complete genome assemblies for M. phaseolina isolates representing the strawberry-specific genotype and another genotype recovered from alfalfa. The strawberry isolate had 59 contigs/scaffolds with an N50 of 4.3 Mb. The isolate from alfalfa had an N50 of 5.0 Mb and 14 nuclear contigs with half including telomeres. Both genomes were annotated with MAKER using transcript evidence generated in this study with over 13,000 protein-coding genes predicted. Unique groups of genes for each isolate were identified when compared to closely related fungal species. Structural comparisons between the isolates reveal large-scale rearrangements including chromosomal inversions and translocations. To include isolates representing a range of pathogen genotypes, an additional 30 isolates were sequenced with Illumina, assembled, and compared to the strawberry genotype assembly. Within the limits of comparing Illumina and PacBio assemblies, no conserved structural rearrangements were identified among the isolates from the strawberry genotype compared to those from other hosts, but some candidate genes were identified that were largely present in isolates of the strawberry genotype and absent in other genotypes. Conclusions: High-quality reference genomes of M. phaseolina have allowed for the identification of structural changes associated with a genotype that has a host preference toward strawberry and will enable future comparative genomics studies. Having more complete assemblies allows for structural rearrangements to be more fully assessed and ensures a greater representation of all the genes. Work with Illumina data from additional isolates suggests that some genes are predominately present in isolates of the strawberry genotype, but additional work is needed to confirm the role of these genes in pathogenesis. Additional work is also needed to complete the scaffolding of smaller contigs identified in the strawberry genotype assembly and to determine if unique genes in the strawberry genotype play a role in pathogenicity.


2020 ◽  
Vol 8 (7) ◽  
pp. 991 ◽  
Author(s):  
Ahmed Mostafa ◽  
Ahmed Kandeil ◽  
Mahmoud Shehata ◽  
Rabeh El Shesheny ◽  
Abdallah M. Samy ◽  
...  

Coronaviruses belong to a large family of viruses that can cause disease outbreaks ranging from the common cold to acute respiratory syndrome. Since 2003, three zoonotic members of this family evolved to cross species barriers infecting humans and resulting in relatively high case fatality rates (CFR). Compared to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV, CFR = 10%) and pandemic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, CFR = 6%), the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has scored the highest CFR (approximately 35%). In this review, we systematically summarize the current state of scientific knowledge about MERS-CoV, including virology and origin, epidemiology, zoonotic mode of transmission, and potential therapeutic or prophylactic intervention modalities.


2014 ◽  
Vol 80 (20) ◽  
pp. 6446-6457 ◽  
Author(s):  
Miguel A. Matilla ◽  
George P. C. Salmond

ABSTRACTMembers of the enterobacterial genusSerratiaare ecologically widespread, and some strains are opportunistic human pathogens. Bacteriophage ϕMAM1 was isolated onSerratia plymuthicaA153, a biocontrol rhizosphere strain that produces the potently bioactive antifungal and anticancer haterumalide oocydin A. The ϕMAM1 phage is a generalized transducing phage that infects multiple environmental and clinical isolates ofSerratiaspp. and a rhizosphere strain ofKluyvera cryocrescens. Electron microscopy allowed classification of ϕMAM1 in the familyMyoviridae. Bacteriophage ϕMAM1 is virulent, uses capsular polysaccharides as a receptor, and can transduce chromosomal markers at frequencies of up to 7 × 10−6transductants per PFU. We also demonstrated transduction of the complete 77-kb oocydin A gene cluster and heterogeneric transduction of a plasmid carrying a type III toxin-antitoxin system. These results support the notion of the potential ecological importance of transducing phages in the acquisition of genes by horizontal gene transfer. Phylogenetic analyses grouped ϕMAM1 within the ViI-like bacteriophages, and genomic analyses revealed that the major differences between ϕMAM1 and other ViI-like phages arise in a region encoding the host recognition determinants. Our results predict that the wider genus of ViI-like phages could be efficient transducing phages, and this possibility has obvious implications for the ecology of horizontal gene transfer, bacterial functional genomics, and synthetic biology.


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