scholarly journals SARS-CoV-2 genomic surveillance identifies naturally occurring truncations of ORF7a that limit immune suppression

2021 ◽  
Author(s):  
Artem Nemudryi ◽  
Anna Nemudraia ◽  
Tanner Wiegand ◽  
Joseph Nichols ◽  
Deann T Snyder ◽  
...  
Keyword(s):  
Immune Suppression ◽  
Immune Modulation ◽  
Viral Suppression ◽  
Interferon Response ◽  
Growth Defect ◽  
List Type ◽  
Whole Genome ◽  
Genome Sequences ◽  
Naturally Occurring ◽  
The World

AbstractOver 200,000 whole genome sequences of SARS-CoV-2 have been determined for viruses isolated from around the world. These sequences have been critical for understanding the spread and evolution of SARS-CoV-2. Using global phylogenomics, we show that mutations frequently occur in the C-terminal end of ORF7a. We have isolated one of these mutant viruses from a patient sample and used viral chal-lenge experiments to demonstrate that Δ115 mutation results in a growth defect. ORF7a has been implicated in immune modulation, and we show that the C-terminal truncation results in distinct changes in interferon stimulated gene expression. Collectively, this work indicates that ORF7a mutations occur frequently and that these changes affect viral mechanisms responsible for suppressing the immune response.HighlightsORF7a mutations are found in SARS-CoV-2 genomes isolated from around the globe.ORF7a mutation results in a replication defect.An ORF7a mutation limits viral suppression of the interferon response.

scholarly journals Changing Molecular Epidemiology of Vibrio cholerae Outbreaks in Shanghai, China

mSystems ◽  
2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Dalong Hu ◽  
Zhiqiu Yin ◽  
Chao Yuan ◽  
Pan Yang ◽  
Chengqian Qian ◽  
...  
Keyword(s):  
Southeast Asia ◽  
East Asia ◽  
Vibrio Cholerae ◽  
Watery Diarrhea ◽  
Whole Genome ◽  
Genome Sequences ◽  
Content Type ◽  
The World ◽  
Pandemic Strains

ABSTRACT The 7th cholera pandemic began in 1961 in Sulawesi, Indonesia, and then spread around the world in at least three waves. However, the lack of genome sequences for Vibrio cholerae strains under long-term surveillance in East Asia, especially in China, has restricted our understanding of the dynamics of the intracountry and intercountry evolution and transmission of the 7th-pandemic clones. In this study, we obtained the genome sequences of 60 V. cholerae strains isolated in Shanghai, the largest port in the world and the largest city in China, from 1961 to 2011. Our whole-genome-based phylogeny of 7th-pandemic strains revealed that all but one fell into five “stages,” most of which are single clades and share independent ancestors. Each stage dominated in succession for a period, with little overlap between them. In addition, two near-identical Shanghai strains belonging to a pre-7th-pandemic precursor and 4 nontoxigenic O1/O139 strains attributed to independent recombination events at the O-antigen loci were present. The major lineages of the 7th pandemic in Shanghai appeared to be closely related to V. cholerae strains isolated from South or Southeast Asia. Stage succession was consistently related to changes in society and human activity, implying that human-caused niche change may play a vital role in the cholera dynamics in Shanghai. IMPORTANCE V. cholerae is the causative agent of cholera, a life-threatening disease characterized by severe, watery diarrhea. The 7th pandemic started in Indonesia in 1961 and spread globally, currently infecting 1.3 million to 4 million people annually. Here, we applied whole-genome sequencing to analyze a long-term collection of V. cholerae clinical strains to reveal the phylogenetic background and evolutionary dynamics of the 7th pandemic in Shanghai, which had undergone breathtakingly rapid development in the last half-century. All but one of the Shanghai 7th-pandemic strains fell into five “stages” that were dominant in Shanghai and appeared to be closely related to 7th-pandemic strains of South or Southeast Asia. Our findings extended the understanding of the dynamics of the evolution and transmission of the 7th-pandemic clones in East Asia and the relationship between social changes and cholera epidemiology.

scholarly journals An African origin for Mycobacterium bovis

2020 ◽  
Vol 2020 (1) ◽  
pp. 49-59 ◽  
Author(s):  
Chloé Loiseau ◽  
Fabrizio Menardo ◽  
Abraham Aseffa ◽  
Elena Hailu ◽  
Balako Gumi ◽  
...  
Keyword(s):  
Population Structure ◽  
West Africa ◽  
Mycobacterium Bovis ◽  
Evolutionary History ◽  
Whole Genome ◽  
Genome Sequences ◽  
The World ◽  
History Of ◽  
Global Population ◽  
Different Parts

Abstract Background and objectives Mycobacterium bovis and Mycobacterium caprae are two of the most important agents of tuberculosis in livestock and the most important causes of zoonotic tuberculosis in humans. However, little is known about the global population structure, phylogeography and evolutionary history of these pathogens. Methodology We compiled a global collection of 3364 whole-genome sequences from M.bovis and M.caprae originating from 35 countries and inferred their phylogenetic relationships, geographic origins and age. Results Our results resolved the phylogenetic relationship among the four previously defined clonal complexes of M.bovis, and another eight newly described here. Our phylogeographic analysis showed that M.bovis likely originated in East Africa. While some groups remained restricted to East and West Africa, others have subsequently dispersed to different parts of the world. Conclusions and implications Our results allow a better understanding of the global population structure of M.bovis and its evolutionary history. This knowledge can be used to define better molecular markers for epidemiological investigations of M.bovis in settings where whole-genome sequencing cannot easily be implemented. Lay summary During the last few years, analyses of large globally representative collections of whole-genome sequences (WGS) from the human-adapted Mycobacterium tuberculosis complex (MTBC) lineages have enhanced our understanding of the global population structure, phylogeography and evolutionary history of these pathogens. In contrast, little corresponding data exists for M. bovis, the most important agent of tuberculosis in livestock. Using whole-genome sequences of globally distributed M. bovis isolates, we inferred the genetic relationships among different M. bovis genotypes distributed around the world. The most likely origin of M. bovis is East Africa according to our inferences. While some M. bovis groups remained restricted to East and West Africa, others have subsequently dispersed to different parts of the world driven by cattle movements.

scholarly journals SARS-CoV-2 ORF3b is a potent interferon antagonist whose activity is further increased by a naturally occurring elongation variant

2020 ◽  
Author(s):  
Yoriyuki Konno ◽  
Izumi Kimura ◽  
Keiya Uriu ◽  
Masaya Fukushi ◽  
Takashi Irie ◽  
...  
Keyword(s):  
Phylogenetic Analyses ◽  
Severe Disease ◽  
Interferon Response ◽  
Type I ◽  
List Type ◽  
Reading Frame ◽  
Naturally Occurring ◽  
C Terminus ◽  
Natural Variant ◽  
Interferon Activity

AbstractOne of the features distinguishing SARS-CoV-2 from its more pathogenic counterpart SARS-CoV is the presence of premature stop codons in its ORF3b gene. Here, we show that SARS-CoV-2 ORF3b is a potent interferon antagonist, suppressing the induction of type I interferon more efficiently than its SARS-CoV ortholog. Phylogenetic analyses and functional assays revealed that SARS-CoV-2-related viruses from bats and pangolins also encode truncated ORF3b gene products with strong anti-interferon activity. Furthermore, analyses of more than 15,000 SARS-CoV-2 sequences identified a natural variant, in which a longer ORF3b reading frame was reconstituted. This variant was isolated from two patients with severe disease and further increased the ability of ORF3b to suppress interferon induction. Thus, our findings not only help to explain the poor interferon response in COVID-19 patients, but also describe a possibility of the emergence of natural SARS-CoV-2 quasispecies with extended ORF3b that may exacerbate COVID-19 symptoms.HighlightsORF3b of SARS-CoV-2 and related bat and pangolin viruses is a potent IFN antagonistSARS-CoV-2 ORF3b suppresses IFN induction more efficiently than SARS-CoV orthologThe anti-IFN activity of ORF3b depends on the length of its C-terminusAn ORF3b with increased IFN antagonism was isolated from two severe COVID-19 cases

scholarly journals De Novo Whole-Genome Sequencing and Annotation of Pathogenic Bovine Pasteurella multocida Type A:3 Strains

2020 ◽  
Vol 9 (49) ◽  
Author(s):  
Morag Livingstone ◽  
Kevin Aitchison ◽  
Mark Dagleish ◽  
David Longbottom
Keyword(s):  
Genome Sequencing ◽  
Pasteurella Multocida ◽  
De Novo ◽  
Whole Genome ◽  
Genome Sequences ◽  
Content Type ◽  
Pneumonic Pasteurellosis ◽  
The United Kingdom ◽  
The World ◽  
Welfare Implications

ABSTRACT Pneumonic pasteurellosis, caused by Pasteurella multocida, is a common respiratory infection of ruminants that has major economic and welfare implications throughout the world. Here, we report the annotated genome sequences of seven pathogenic strains of P. multocida that were isolated from cattle in the United Kingdom.

scholarly journals Whole-Genome Sequences of Two Human Norovirus GII.4 Variants Isolated in the United States

2018 ◽  
Vol 7 (1) ◽  
Author(s):  
Yuan Hu ◽  
Haifeng Chen
Keyword(s):  
United States ◽  
Complete Genome ◽  
The United States ◽  
Whole Genome ◽  
Genome Sequences ◽  
Human Norovirus ◽  
Genotype 4 ◽  
The World ◽  
Stool Specimens ◽  
Norovirus Gii

Variants of human noroviruses belonging to the genogroup II genotype 4 (GII.4) lineage have accounted for most norovirus outbreaks in the world since the mid-1990s. We report here the complete genome sequences of two historical human norovirus GII.4 variants isolated from norovirus-positive patient stool specimens in the United States.

scholarly journals In silico comparative genomics of SARS-CoV-2 to determine the source and diversity of the pathogen in Bangladesh

2020 ◽  
Author(s):  
Tushar Ahmed Shishir ◽  
Iftekhar Bin Naser ◽  
Shah M. Faruque
Keyword(s):  
Phylogenetic Analysis ◽  
Protein Structures ◽  
Spike Protein ◽  
Whole Genome ◽  
Missense Mutations ◽  
Coding Region ◽  
Genome Sequences ◽  
Genomic Variations ◽  
Southern District ◽  
The World

AbstractThe COVID19 pandemic caused by SARS-CoV-2 virus has severely affected most countries of the world including Bangladesh. We conducted comparative analysis of publicly available whole-genome sequences of 64 SARS-CoV-2 isolates in Bangladesh and 371 isolates from another 27 countries to predict possible transmission routes of COVID19 to Bangladesh and genomic variations among the viruses. Phylogenetic analysis indicated that the pathogen was imported in Bangladesh from multiple countries. The viruses found in the southern district of Chattogram were closely related to strains from Saudi Arabia whereas those in Dhaka were similar to that of United Kingdom and France. The 64 SARS-CoV-2 sequences from Bangladesh belonged to three clusters. Compared to the ancestral SARS-CoV-2 sequence reported from China, the isolates in Bangladesh had a total of 180 mutations in the coding region of the genome, and 110 of these were missense. Among these, 99 missense mutations (90%) were predicted to destabilize protein structures. Remarkably, a mutation that leads to an I300F change in the nsp2 protein and a mutation leading to D614G change in the spike protein were prevalent in SARS-CoV-2 genomic sequences, and might have influenced the epidemiological properties of the virus in Bangladesh.

scholarly journals In silico comparative genomics of SARS-CoV-2 to determine the source and diversity of the pathogen in Bangladesh

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245584
Author(s):  
Tushar Ahmed Shishir ◽  
Iftekhar Bin Naser ◽  
Shah M. Faruque
Keyword(s):  
Phylogenetic Analysis ◽  
Protein Structures ◽  
Spike Protein ◽  
Whole Genome ◽  
Missense Mutations ◽  
Coding Region ◽  
Genome Sequences ◽  
Genomic Variations ◽  
Southern District ◽  
The World

The COVID19 pandemic caused by SARS-CoV-2 virus has severely affected most countries of the world including Bangladesh. We conducted comparative analysis of publicly available whole-genome sequences of 64 SARS-CoV-2 isolates in Bangladesh and 371 isolates from another 27 countries to predict possible transmission routes of COVID19 to Bangladesh and genomic variations among the viruses. Phylogenetic analysis indicated that the pathogen was imported in Bangladesh from multiple countries. The viruses found in the southern district of Chattogram were closely related to strains from Saudi Arabia whereas those in Dhaka were similar to that of United Kingdom and France. The 64 SARS-CoV-2 sequences from Bangladesh belonged to three clusters. Compared to the ancestral SARS-CoV-2 sequence reported from China, the isolates in Bangladesh had a total of 180 mutations in the coding region of the genome, and 110 of these were missense. Among these, 99 missense mutations (90%) were predicted to destabilize protein structures. Remarkably, a mutation that leads to an I300F change in the nsp2 protein and a mutation leading to D614G change in the spike protein were prevalent in SARS-CoV-2 genomic sequences, and might have influenced the epidemiological properties of the virus in Bangladesh.

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