scholarly journals Recombination Events and Conserved Nature of Receptor Binding Motifs in Coxsackievirus A9 Isolates

Viruses ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 68 ◽  
Author(s):  
Eero Hietanen ◽  
Petri Susi
Keyword(s):  
Clinical Data ◽  
Receptor Binding ◽  
Genetic Relationships ◽  
Phylogenetic Analyses ◽  
Sequence Evolution ◽  
Vp1 Gene ◽  
Nonstructural Proteins ◽  
Rgd Motif ◽  
Coxsackievirus A9 ◽  
Vp1 Capsid Protein

Coxsackievirus A9 (CVA9) is an enterically transmitted enterovirus and one of the most pathogenic type among human enteroviruses. CVA9 isolates use a distinctive RGD (Arg-Gly-Asp) motif within VP1 capsid protein that defines its ability to bind to integrin receptor(s) for cellular entry. To investigate CVA9 evolution and pathogenicity, genetic relationships and recombination events were analyzed between 54 novel clinical isolates of CVA9, as well as 21 previously published full length CVA9 sequences from GenBank. Samples were investigated by partial sequencing of the novel VP1 and 3Dpol genes, as well as including the corresponding areas from GenBank sequences. Phylogenetic analyses were combined with clinical data in a further attempt to analyze whether sequence evolution reflects CVA9 pathogenicity in the phylogenies. Furthermore, VP1 gene was also analyzed for receptor binding sites including the RGD motif and the putative heparan sulfate (HS) site. Analysis of the 559-nucleotide-long VP1 sequences identified six clades. Although most of the strains within each clade showed geographical clustering, the grouping pattern of the isolates in the analysis of the VP1 gene was strikingly different from grouping of 3Dpol, which suggests that recombination events may have occurred in the region encoding the nonstructural proteins. Inclusion of clinical data did not provide any evidence of symptom based phylogenetic clustering of CVA9 isolates. Amino acid sequence analysis of the VP1 polypeptide demonstrated that the RGD motif was fully conserved among the isolates while the putative HS binding site was only found in one isolate. These data suggest that integrin binding is essential for virus tropism, but do not explain the symptom repertoire.

Molecular epidemiology and evolution of coxsackievirus A9

Microbiology ◽  
2000 ◽  
Vol 81 (5) ◽  
pp. 1361-1372 ◽  
Author(s):  
Juhana Santti ◽  
Heli Harvala ◽  
Leena Kinnunen ◽  
Timo Hyypiä
Keyword(s):  
Genetic Relationships ◽  
Amino Acid Sequences ◽  
Sequencing Analysis ◽  
Nonstructural Proteins ◽  
Geographical Regions ◽  
Coxsackievirus A9 ◽  
Phylogenetic Grouping ◽  
Grouping Pattern ◽  
Arginine Glycine Aspartic Acid ◽  
Phylogenetic Lineages

Genetic relationships between 35 clinical isolates of coxsackievirus A9 (CAV9), collected during the last five decades from different geographical regions, were investigated by partial sequencing. Analysis of a 150 nucleotide sequence at the VP1/2A junction region identified 12 CAV9 genotypes. While most of the strains within each genotype showed geographical clustering, the analysis also provided evidence for long-range importation of virus strains. Phylogenetic analysis of a longer region around the VP1/2A junction (approximately 390 nucleotides) revealed that the designated genotypes actually represented phylogenetic lineages. The phylogenetic grouping pattern of the isolates in the analysis of the VP4/VP2 region was similar to that obtained in the VP1/2A region whereas analysis of the 3D region indicated a strikingly different grouping, which suggests that recombination events may occur in the region encoding the nonstructural proteins. Analysis of the deduced amino acid sequences of the VP1 polypeptide demonstrated that the RGD (arginine-glycine-aspartic acid) motif, implicated in the interaction of the virus with integrin, was fully conserved among the isolates.

scholarly journals Genotyping-by-Sequencing of Gossypium hirsutum Races and Cultivars Uncovers Novel Patterns of Genetic Relationships and Domestication Footprints

2019 ◽  
Vol 15 ◽  
pp. 117693431988994
Author(s):  
Shulin Zhang ◽  
Yaling Cai ◽  
Jinggong Guo ◽  
Kun Li ◽  
Renhai Peng ◽  
...  
Keyword(s):  
Gossypium Hirsutum ◽  
Genetic Relationships ◽  
Phylogenetic Analyses ◽  
Genotyping By Sequencing ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Breeding Programs ◽  
Association Analyses ◽  
Genome Wide ◽  
Candidate Gene Locus

Determining the genetic rearrangement and domestication footprints in Gossypium hirsutum cultivars and primitive race genotypes are essential for effective gene conservation efforts and the development of advanced breeding molecular markers for marker-assisted breeding. In this study, 94 accessions representing the 7 primitive races of G hirsutum, along with 9 G hirsutum and 12 Gossypium barbadense cultivated accessions were evaluated. The genotyping-by-sequencing (GBS) approach was employed and 146 558 single nucleotide polymorphisms (SNP) were generated. Distinct SNP signatures were identified through the combination of selection scans and association analyses. Phylogenetic analyses were also conducted, and we concluded that the Latifolium, Richmondi, and Marie-Galante race accessions were more genetically related to the G hirsutum cultivars and tend to cluster together. Fifty-four outlier SNP loci were identified by selection-scan analysis, and 3 SNPs were located in genes related to the processes of plant responding to stress conditions and confirmed through further genome-wide signals of marker-phenotype association analysis, which indicate a clear selection signature for such trait. These results identified useful candidate gene locus for cotton breeding programs.

scholarly journals Genetic Differentiation Associated with Fumonisin and Gibberellin Production in JapaneseFusarium fujikuroi

2018 ◽  
Vol 85 (1) ◽  
Author(s):  
Haruhisa Suga ◽  
Mitsuhiro Arai ◽  
Emi Fukasawa ◽  
Keiichi Motohashi ◽  
Hiroyuki Nakagawa ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Genetic Relationships ◽  
Pathogenic Fungus ◽  
Phylogenetic Analyses ◽  
Aflp Markers ◽  
Fusarium Fujikuroi ◽  
Rice Seedlings ◽  
Bakanae Disease ◽  
Content Type ◽  
Gibberellin Production

ABSTRACTFusarium fujikuroiis a pathogenic fungus that infects rice. It produces several important mycotoxins, such as fumonisins. Fumonisin production has been detected in strains of maize, strawberry, and wheat, whereas it has not been detected in strains from rice seedlings infested with bakanae disease in Japan. We investigated the genetic relationships, pathogenicity, and resistance to a fungicide, thiophanate-methyl (TM), in 51 fumonisin-producing strains and 44 nonproducing strains. Phylogenetic analyses based on amplified fragment length polymorphism (AFLP) markers and two specific genes (a combined sequence of translation elongation factor 1α [TEF1α] and RNA polymerase II second-largest subunit [RPB2]) indicated differential clustering between the fumonisin-producing and -nonproducing strains. One of the AFLP markers, EATMCAY107, was specifically present in the fumonisin-producing strains. A specific single nucleotide polymorphism (SNP) between the fumonisin-producing and nonproducing strains was also detected inRPB2, in addition to an SNP previously found inTEF1α. Gibberellin production was higher in the nonproducing than in the producing strains according to anin vitroassay, and the nonproducing strains had the strongest pathogenicity with regard to rice seedlings. TM resistance was closely correlated with the cluster of fumonisin-nonproducing strains. The results indicate that intraspecific evolution in JapaneseF. fujikuroiis associated with fumonisin production and pathogenicity. Two subgroups of JapaneseF. fujikuroi, designated G group and F group, were distinguished based on phylogenetic differences and the high production of gibberellin and fumonisin, respectively.IMPORTANCEFusarium fujikuroiis a pathogenic fungus that causes rice bakanae disease. Historically, this pathogen has been known asFusarium moniliforme, along with many other species based on a broad species concept. Gibberellin, which is currently known as a plant hormone, is a virulence factor ofF. fujikuroi. Fumonisin is a carcinogenic mycotoxin posing a serious threat to food and feed safety. Although it has been confirmed thatF. fujikuroiproduces gibberellin and fumonisin, production varies among strains, and individual production has been obscured by the traditional appellation ofF. moniliforme, difficulties in species identification, and variation in the assays used to determine the production of these secondary metabolites. In this study, we discovered two phylogenetic subgroups associated with fumonisin and gibberellin production in JapaneseF. fujikuroi.

Genetic relationships of eight species of Pacific tunas (Teleostei: Scombridae) inferred from allozyme analysis

1995 ◽  
Vol 46 (7) ◽  
pp. 1021 ◽  
Author(s):  
NG Elliott ◽  
RD Ward
Keyword(s):  
Liver Enzymes ◽  
Genetic Relationships ◽  
Phylogenetic Analyses ◽  
Allozyme Variation ◽  
Allozyme Analysis ◽  
Average Heterozygosity ◽  
Katsuwonus Pelamis ◽  
Thunnus Alalunga ◽  
Auxis Thazard ◽  
Allozyme Loci

A phylogenetic analysis of eight species of Pacific tunas was made after examining allozyme variation at 23 muscle and liver enzymes encoded by 35 loci. The eight species of tuna were: Thunnus alalunga, albacore; T. obesus, bigeye; T. thynnus orientalis, northern bluefin; T. maccoyii, southern bluefin; T. albacares, yellowfin; Auxis thazard, frigate; Euthynnus affiizii kawakawa; Katsuwonus pelamis, skipjack. All species except the northern bluefin were also examined for variation at three eye-specific loci. The average heterozygosity per locus ranged from 0.038 (frigate) to 0.070 (bigeye). Genetic relationships were examined on the basis of the 35 loci screened in all species. Genetic identities among the five Thunnus species were high, averaging 0.864 and ranging from 0.788 to 0.923. Whereas the albacore appeared to be the most divergent of the Thunnus species (mean identity to other Thunnus species of 0.825, range 0.788-0.452), there was little differentiation between yellowfin, southern bluefin and northern bluefin tunas (mean identity 0.905, range 0.892-0.923), and phylogenetic analyses failed to resolve the branch order among the Thunnus species. The non-Thunnus tunas were quite divergent both from one another and from Thunnus species (mean identity 0.358, range 0.280-0.606). Diagnostic allozyme loci were identified, allowing the discrimination of all species.

scholarly journals An experimentally informed evolutionary model improves phylogenetic fit to divergent lactamase homologs

2014 ◽  
Author(s):  
Jesse D Bloom
Keyword(s):  
High Throughput ◽  
Phylogenetic Analyses ◽  
Sequence Divergence ◽  
Evolutionary Model ◽  
Molecular Data ◽  
Quantitative Model ◽  
Sequence Evolution ◽  
Beta Lactamase ◽  
Evolutionary Models ◽  
High Throughput Experiments

Phylogenetic analyses of molecular data require a quantitative model for how sequences evolve. Traditionally, the details of the site-specific selection that governs sequence evolution are not knowna priori, making it challenging to create evolutionary models that adequately capture the heterogeneity of selection at different sites. However, recent advances in high-throughput experiments have made it possible to quantify the effects of all single mutations on gene function. I have previously shown that such high-throughput experiments can be combined with knowledge of underlying mutation rates to create a parameter-free evolutionary model that describes the phylogeny of influenza nucleoprotein far better than commonly used existing models. Here I extend this work by showing that published experimental data on TEM-1 beta-lactamase (Firnberg et al, 2014) can be combined with a few mutation rate parameters to create an evolutionary model that describes beta-lactamase phylogenies much than most common existing models. This experimentally informed evolutionary model is superior even for homologs that are substantially diverged (about 35% divergence at the protein level) from the TEM-1 parent that was the subject of the experimental study. These results suggest that experimental measurements can inform phylogenetic evolutionary models that are applicable to homologs that span a substantial range of sequence divergence.

scholarly journals SARS-CoV-2 spike protein unlikely to bind to integrins via the Arg-Gly-Asp (RGD) motif of the Receptor Binding Domain: evidence from structural analysis and microscale accelerated molecular dynamics

2021 ◽  
Author(s):  
Houcemeddine Othman ◽  
Haifa Ben Messaoud ◽  
Oussema Khamessi ◽  
Hazem Ben Mabrouk ◽  
Kais Ghedira ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Structural Analysis ◽  
Receptor Binding ◽  
Normal Mode Analysis ◽  
Protein Docking ◽  
Binding Domain ◽  
Mode Analysis ◽  
Receptor Binding Domain ◽  
Rgd Motif ◽  
Accelerated Molecular Dynamics

The Receptor Binding Domain (RBD) of SARS-CoV-2 virus harbors a sequence of Arg-Gly-Asp tripeptide named RGD motif, which has also been identified in extracellular matrix proteins that bind integrins as well as other disintegrins and viruses. Accordingly, integrins have been proposed as host receptors for SARS-CoV-2. The hypothesis was supported by sequence and structural analysis. However, given that the microenvironment of the RGD motif imposes structural hindrance to the protein-protein association, the validity of this hypothesis is still uncertain. Here, we used normal mode analysis, accelerated molecular dynamics microscale simulation, and protein-protein docking to investigate the putative role of RGD motif of SARS-CoV-2 RBD for interacting with integrins. We found, by molecular dynamics, that neither RGD motif nore its microenvironment show any significant conformational shift in the RBD structure. Highly populated clusters were used to run a protein-protein docking against three RGD-binding integrin types, showing no capability of the RBD domain to interact with the RGD binding site. Moreover, the free energy landscape revealed that the RGD conformation within RBD could not acquire an optimal geometry to allow the interaction with integrins. Our results highlighted different structural features of the RGD motif that may prevent its involvement in the interaction with integrins. We, therefore, suggest, in the case where integrins are confirmed to be the direct host receptors for SARS-CoV-2, a possible involvement of other residues to stabilize the interaction.

scholarly journals Can the SARS-CoV-2 Spike Protein Bind Integrins Independent of the RGD Sequence?

2021 ◽  
Vol 11 ◽  
Author(s):  
Christopher A. Beaudoin ◽  
Samir W. Hamaia ◽  
Christopher L.-H. Huang ◽  
Tom L. Blundell ◽  
Antony P. Jackson
Keyword(s):  
Receptor Binding ◽  
Conformational Changes ◽  
Sequence Similarity ◽  
Binding Domain ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Binding Motifs ◽  
Rgd Motif ◽  
Rgd Sequence ◽  
Protein Receptor

The RGD motif in the Severe Acute Syndrome Coronavirus 2 (SARS-CoV-2) spike protein has been predicted to bind RGD-recognizing integrins. Recent studies have shown that the spike protein does, indeed, interact with αVβ3 and α5β1 integrins, both of which bind to RGD-containing ligands. However, computational studies have suggested that binding between the spike RGD motif and integrins is not favourable, even when unfolding occurs after conformational changes induced by binding to the canonical host entry receptor, angiotensin-converting enzyme 2 (ACE2). Furthermore, non-RGD-binding integrins, such as αx, have been suggested to interact with the SARS-CoV-2 spike protein. Other viral pathogens, such as rotaviruses, have been recorded to bind integrins in an RGD-independent manner to initiate host cell entry. Thus, in order to consider the potential for the SARS-CoV-2 spike protein to bind integrins independent of the RGD sequence, we investigate several factors related to the involvement of integrins in SARS-CoV-2 infection. First, we review changes in integrin expression during SARS-CoV-2 infection to identify which integrins might be of interest. Then, all known non-RGD integrin-binding motifs are collected and mapped to the spike protein receptor-binding domain and analyzed for their 3D availability. Several integrin-binding motifs are shown to exhibit high sequence similarity with solvent accessible regions of the spike receptor-binding domain. Comparisons of these motifs with other betacoronavirus spike proteins, such as SARS-CoV and RaTG13, reveal that some have recently evolved while others are more conserved throughout phylogenetically similar betacoronaviruses. Interestingly, all of the potential integrin-binding motifs, including the RGD sequence, are conserved in one of the known pangolin coronavirus strains. Of note, the most recently recorded mutations in the spike protein receptor-binding domain were found outside of the putative integrin-binding sequences, although several mutations formed inside and close to one motif, in particular, may potentially enhance binding. These data suggest that the SARS-CoV-2 spike protein may interact with integrins independent of the RGD sequence and may help further explain how SARS-CoV-2 and other viruses can evolve to bind to integrins.

scholarly journals Genome analysis of Spiroplasma citri strains from different host plants and its leafhopper vectors

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Rachel Rattner ◽  
Shree Prasad Thapa ◽  
Tyler Dang ◽  
Fatima Osman ◽  
Vijayanandraj Selvaraj ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Host Range ◽  
Genetic Relationships ◽  
Phylogenetic Analyses ◽  
The United States ◽  
Weed Species ◽  
Protein Coding ◽  
Spiroplasma Citri ◽  
Beet Leafhopper ◽  
Separate Branch

Abstract Background Spiroplasma citri comprises a bacterial complex that cause diseases in citrus, horseradish, carrot, sesame, and also infects a wide array of ornamental and weed species. S. citri is transmitted in a persistent propagative manner by the beet leafhopper, Neoaliturus tenellus in North America and Circulifer haematoceps in the Mediterranean region. Leafhopper transmission and the pathogen’s wide host range serve as drivers of genetic diversity. This diversity was examined in silico by comparing the genome sequences of seven S. citri strains from the United States (BR12, CC-2, C5, C189, LB 319, BLH-13, and BLH-MB) collected from different hosts and times with other publicly available spiroplasmas. Results Phylogenetic analysis using 16S rRNA sequences from 39 spiroplasmas obtained from NCBI database showed that S. citri strains, along with S. kunkelii and S. phoeniceum, two other plant pathogenic spiroplasmas, formed a monophyletic group. To refine genetic relationships among S. citri strains, phylogenetic analyses with 863 core orthologous sequences were performed. Strains that clustered together were: CC-2 and C5; C189 and R8-A2; BR12, BLH-MB, BLH-13 and LB 319. Strain GII3–3X remained in a separate branch. Sequence rearrangements were observed among S. citri strains, predominantly in the center of the chromosome. One to nine plasmids were identified in the seven S. citri strains analyzed in this study. Plasmids were most abundant in strains isolated from the beet leafhopper, followed by strains from carrot, Chinese cabbage, horseradish, and citrus, respectively. All these S. citri strains contained one plasmid with high similarity to plasmid pSci6 from S. citri strain GII3–3X which is known to confer insect transmissibility. Additionally, 17 to 25 prophage-like elements were identified in these genomes, which may promote rearrangements and contribute to repetitive regions. Conclusions The genome of seven S. citri strains were found to contain a single circularized chromosome, ranging from 1.58 Mbp to 1.74 Mbp and 1597–2232 protein-coding genes. These strains possessed a plasmid similar to pSci6 from the GII3–3X strain associated with leafhopper transmission. Prophage sequences found in the S. citri genomes may contribute to the extension of its host range. These findings increase our understanding of S. citri genetic diversity.

scholarly journals Genetic characterization of a novel picornavirus in turkeys (Meleagris gallopavo) distinct from turkey galliviruses and megriviruses and distantly related to the members of the genus Avihepatovirus

2013 ◽  
Vol 94 (7) ◽  
pp. 1496-1509 ◽  
Author(s):  
Ákos Boros ◽  
Csaba Nemes ◽  
Péter Pankovics ◽  
Beatrix Kapusinszky ◽  
Eric Delwart ◽  
...  
Keyword(s):  
Complete Genome ◽  
Hepatitis A Virus ◽  
Phylogenetic Analyses ◽  
Meleagris Gallopavo ◽  
Amino Acid Identity ◽  
Entry Site ◽  
Duck Hepatitis ◽  
Capsid Protein Vp1 ◽  
Vp1 Capsid Protein

This study reports the metagenomic detection and complete genome characterization of a novel turkey picornavirus from faecal samples of healthy (1/3) and affected (6/8) commercial turkeys with enteric and/or stunting syndrome in Hungary. The virus was detected at seven of the eight farms examined. The turkey/M176-TuASV/2011/HUN genome (KC465954) was genetically different from the currently known picornaviruses of turkey origin (megriviruses and galliviruses), and showed distant phylogenetic relationship and common genomic features (e.g. uncleaved VP0 and three predicted and unrelated 2A polypeptides) to duck hepatitis A virus (DHAV) of the genus Avihepatovirus. The complete genome analysis revealed multiple distinct genome features like the presence of two in-tandem aphthovirus 2A-like sequence repeats with DxExNPG/P ‘ribosome-skipping’ sites (76 %, 23/30 amino acids identical), with the first aphthovirus 2A-like sequence being located at the end of the VP1 capsid protein (VP1/2A1 ‘ribosome-skipping’ site). The phylogenetic analyses, low sequence identity (33, 32 and 36 % amino acid identity in P1, P2 and P3 regions) to DHAV, and the type II-like internal ribosome entry site suggests that this turkey picornavirus is related to, but distinct from the genus Avihepatovirus and it could be the founding member of a novel Avihepatovirus sister-clade genus. This is the third, taxonomically highly distinct picornavirus clade identified from turkeys exhibiting varied symptoms.

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