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1.
Nat Commun ; 12(1): 2031, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33795676

RESUMEN

Patient-derived xenografts are crucial for drug development but their use is challenged by issues such as murine viral infection. We evaluate the scope of viral infection and its impact on patient-derived xenografts by taking an unbiased data-driven approach to analyze unmapped RNA-Seq reads from 184 experiments. We find and experimentally validate the extensive presence of murine viral sequence reads covering entire viral genomes in patient-derived xenografts. The existence of viral sequences inside tumor cells is further confirmed by single cell sequencing data. Extensive chimeric reads containing both viral and human sequences are also observed. Furthermore, we find significantly changed expression levels of many cancer-, immune-, and drug metabolism-related genes in samples with high virus load. Our analyses indicate a need to carefully evaluate the impact of viral infection on patient-derived xenografts for drug development. They also point to a need for attention to quality control of patient-derived xenograft experiments.


Asunto(s)
Genoma Viral/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Neoplasias/genética , Análisis de Secuencia de ADN/métodos , Ensayos Antitumor por Modelo de Xenoinjerto/métodos , Animales , Línea Celular Tumoral , Productos del Gen env/clasificación , Productos del Gen env/genética , Productos del Gen gag/clasificación , Productos del Gen gag/genética , Xenoinjertos/metabolismo , Xenoinjertos/virología , Humanos , Ratones , Neoplasias/clasificación , Neoplasias/virología , Filogenia , Virosis/genética , Virosis/virología
2.
Molecules ; 26(5)2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33652602

RESUMEN

Hepatitis B virus (HBV) is a circular, and partially double-stranded DNA virus. Upon infection, the viral genome is translocated into the cell nucleus, generating the covalently closed circular DNA (cccDNA) intermediate, and forming a mini chromosome. HBV HBx is a small protein displaying multiple roles in HBV-infected cells, and in different subcellular locations. In the nucleus, the HBx protein is required to initiate and maintain viral transcription from the viral mini chromosome. In contrast, HBx also functions in the cytoplasm, where it is able to alter multiple cellular functions such as mitochondria metabolism, apoptosis and signal transduction pathways. It has been reported that in cultured cells, at low expression levels, the HBx protein is localized in the nucleus, whereas at high expression levels, it accumulates in the cytoplasm. This dynamic subcellular distribution of HBx might be essential to exert its multiple roles during viral infection. However, the mechanism that regulates different subcellular localizations of the HBx protein is unknown. We have previously taken a bioinformatics approach to investigate whether HBx might be regulated via post-translational modification, and we have proposed that the multiple nucleocytoplasmic functions of HBx might be regulated by an evolutionarily conserved mechanism via phosphorylation. In the current study, phylogenetically conserved amino acids of HBx with a high potential of phosphorylation were targeted for site-directed mutagenesis. Two conserved serine (Ser25 and Ser41), and one conserved threonine (Thr81) amino acids were replaced by either alanine or aspartic acid residues to simulate an unphosphorylated or phosphorylated state, respectively. Human hepatoma cells were transfected with increasing amounts of the HBx DNA constructs, and the cells were analyzed by fluorescence microscopy. Together, our results show that the nucleocytoplasmic distribution of the HBx protein could be regulated by phosphorylation since some of the modified proteins were mainly confined to distinct subcellular compartments. Remarkably, both HBx Ser41A, and HBx Thr81D proteins were predominantly localized within the nuclear compartment throughout the different expression levels of HBx mutants.


Asunto(s)
Carcinoma Hepatocelular/genética , Hepatitis B/genética , Neoplasias Hepáticas/genética , Transactivadores/genética , Proteínas Reguladoras y Accesorias Virales/genética , Secuencia de Aminoácidos/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , Secuencia Conservada/genética , Regulación Viral de la Expresión Génica/genética , Genoma Viral/genética , Células Hep G2 , Hepatitis B/patología , Hepatitis B/virología , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/patogenicidad , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Fosforilación/genética , Filogenia
3.
Arch Virol ; 166(5): 1409-1414, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33646405

RESUMEN

Common bean plants (Phaseolus vulgaris L.) showing different virus-like symptoms were collected in northwestern Argentina. Dot-blot hybridization tests showed that the begomoviruses bean golden mosaic virus and tomato yellow vein streak virus were the most prevalent, but they also revealed the presence of unknown begomoviruses. The complete genome sequence of one of these unknown begomoviruses was determined. Sequence analysis showed that the virus is a typical New World begomovirus, for which the name "bean bushy stunt virus" (BBSV) is proposed. Biological assays based on biolistic inoculations showed that BBSV induced leaf roll and stunting symptoms similar to those observed in the field-collected common bean sample.


Asunto(s)
Begomovirus/fisiología , Phaseolus/virología , Enfermedades de las Plantas/virología , Argentina , Secuencia de Bases , Begomovirus/clasificación , Begomovirus/genética , Begomovirus/patogenicidad , ADN Viral/genética , Genoma Viral/genética , Especificidad del Huésped , Sistemas de Lectura Abierta , Phaseolus/crecimiento & desarrollo , Filogenia , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/virología , Soja/crecimiento & desarrollo , Soja/virología
4.
Arch Virol ; 166(5): 1495-1499, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33646407

RESUMEN

The complete genome sequence of a new polerovirus found naturally infecting Artemisia princeps, artemisia virus B (ArtVB), was determined using high-throughput sequencing. The ArtVB genome comprises 6,141 nucleotides and contains six putative open reading frames (ORF0 to ORF5) with a genome structure typical of poleroviruses. A multiple sequence alignment showed that the complete ArtVB genome shares 50.98% nucleotide sequence identity with ixeridium yellow mottle virus 1 (IxYMaV-1, GenBank accession no. KT868949). ArtVB shares the highest amino acid sequence identity in P0 and P3-P5 (21.54%-51.69%) with other known poleroviruses. Phylogenetic analysis indicated that ArtVB should be considered a member of a new species within the genus Polerovirus, family Luteoviridae.


Asunto(s)
Artemisia/virología , Genoma Viral/genética , Luteoviridae/genética , Secuencia de Bases , Luteoviridae/clasificación , Sistemas de Lectura Abierta , Filogenia , Enfermedades de las Plantas/virología , ARN Viral/genética , República de Corea , Proteínas Virales/genética
5.
Arch Virol ; 166(5): 1501-1505, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33677680

RESUMEN

The genus Carlavirus (family Betaflexiviridae, order Tymovirales) currently includes 53 species recognized by the ICTV. The NCBI GenBank database has 43 full-length carlavirus genome sequences (7,890 to 9,073 nt). Surprisingly, the type species Carnation latent virus is not associated with a complete genome sequence of a carnation latent virus (CLV) isolate; GenBank only has accessions with 1313 or fewer nucleotides. The goal of this study was to determine the full-length genome sequence of CLV. Naturally infected greenhouse-grown 'Kiwi Lace' carnation plants that tested positive for CLV by ELISA and RT-PCR were used as source plants for high-throughput sequencing, completed by 5' and 3' RACE and validated by Sanger sequencing of CLV-specific RT-PCR-generated amplicons. The complete CLV-KL sequence (MN450069) was determined to be 8,513 nt in length. In pairwise analysis, the genome shares 40-46% identity with recognized carlaviruses and the six in silico-translated proteins have 15-62% amino acid sequence identity to their respective carlavirus orthologs. The CLV-KL coat protein shares 98.4% identity with the NCBI reference sequence CLV-UK. In phylogenetic analysis, CLV clusters with butterbur mosaic virus, coleus vein necrosis virus, and garlic common latent virus. This is the first report of the full genome sequence of an isolate of carnation latent virus, the type member of the genus Carlavirus.


Asunto(s)
Carlavirus/genética , Dianthus/virología , Genoma Viral/genética , Secuencia de Aminoácidos , Secuencia de Bases , Carlavirus/clasificación , Carlavirus/aislamiento & purificación , Mapeo Cromosómico , Sistemas de Lectura Abierta , Filogenia , Enfermedades de las Plantas/virología , ARN Viral/genética , Proteínas Virales/genética
6.
Arch Virol ; 166(5): 1427-1431, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33682071

RESUMEN

Potato aucuba mosaic virus (PAMV), a positive single-strand RNA virus, has one of the longest genomes of the viruses in the genus Potexvirus. In 2019, potato samples with mottle and crinkling symptoms from Huzhou, Zhejiang province, China, were identified to be infected with PAMV, potato virus X (PVX), and potato virus Y (PVY) by transcriptome sequencing. To study the effects of single infection by PAMV, the full-length sequence of PAMV from Huzhou (MT193476) was determined and an infectious full-length cDNA clone was constructed. This cDNA clone was infectious by agro-infiltration, leading to systemic symptoms in Nicotiana benthamiana, tomato, pepper, and potato.


Asunto(s)
Potexvirus/genética , Potexvirus/patogenicidad , Clonación Molecular , ADN Complementario , Genoma Viral/genética , Filogenia , Enfermedades de las Plantas/virología , Plantas/clasificación , Plantas/virología , Potexvirus/clasificación , Potexvirus/aislamiento & purificación , ARN Viral/genética , Genética Inversa , Solanum tuberosum/virología
7.
Arch Virol ; 166(5): 1507-1511, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33683472

RESUMEN

In this study, we isolated and determined the complete genome sequence of a novel mitovirus, "Botryosphaeria dothidea mitovirus 2" (BdMV2), from the phytopathogenic fungus Botryosphaeria dothidea isolate DT-5. BdMV2 has a genome 2,482 nt in length with an A+U content of 67%. The genome of BdMV2 contains a single large open reading frame (ORF) encoding an RNA-dependent RNA polymerase (RdRp) of 717 amino acids (aa) with a molecular mass of 81.86 kDa. A BLASTp comparison of the RdRp sequence showed the highest identity (66.67%) with that of Alternaria arborescens mitovirus 1 (AbMV1). Sequence comparisons and phylogenetic analysis revealed that BdMV2 is a new member of the genus Mitovirus of the family Mitoviridae.


Asunto(s)
Ascomicetos/virología , Virus Fúngicos/clasificación , Enfermedades de las Plantas/microbiología , Virus ARN/clasificación , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Ascomicetos/aislamiento & purificación , Secuencia de Bases , Virus Fúngicos/genética , Genoma Viral/genética , Sistemas de Lectura Abierta , Filogenia , Enfermedades de las Plantas/virología , Virus ARN/genética , ARN Viral/genética , Rosaceae/microbiología , Rosaceae/virología , Proteínas Virales/genética
8.
Arch Virol ; 166(5): 1513-1515, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33686515

RESUMEN

A novel virus was identified in aconite (Aconitum carmichaelii Debx.) in China by high-throughput sequencing (HTS) and tentatively named "aconite virus A" (AcVA). The genomic RNA of AcVA consists of 8,844 nucleotides, excluding the poly(A) at the 3' end. Analysis of the genomic organization of AcVA indicated that it possesses a genomic structure that is typical of carlaviruses and contains six putative open reading frames (ORFs). Pairwise analysis revealed that the replicase and coat protein of AcVA share the highest amino acid sequence identity (43.78% and 57.01%) with those of coleus vein necrosis virus (CVNV) and butterbur mosaic virus (ButMV), respectively. Based on the current classification criteria for carlaviruses, AcVA should be considered a distinct member of the genus Carlavirus.


Asunto(s)
Aconitum/virología , Carlavirus/genética , Genoma Viral/genética , Secuencia de Aminoácidos , Secuencia de Bases , Carlavirus/clasificación , China , Sistemas de Lectura Abierta , Filogenia , Enfermedades de las Plantas/virología , Plantas Medicinales/virología , ARN Viral/genética , Proteínas Virales/genética
9.
Arch Virol ; 166(5): 1517-1520, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33694004

RESUMEN

The subfamily Parvovirinae within the family Parvoviridae consists of viruses that can infect a wide range of vertebrate hosts and cause effects ranging from severe disease to asymptomatic infection. In the present study, high-throughput sequencing (HTS) was utilized to analyze samples obtained from an abortion outbreak in a sheep flock to identify a putative viral etiology. A highly divergent nearly complete parvovirid genome sequence, approximately 4.9 kb in length, was determined. The nonstructural protein (NS1) amino acid (aa) sequence of this virus shared less than 30% identity with those of other copiparvoviruses and less than 22% identity with those of members of other genera in the subfamily Parvovirinae. Phylogenetically, this virus, which we have provisionally named "sheep copiparvovirus 1", formed a cluster with copiparvovirus sequences and should be classified as a member of a new species in the genus Copiparvovirus.


Asunto(s)
Infecciones por Parvoviridae/veterinaria , Parvovirinae/genética , Enfermedades de las Ovejas/virología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Brasil/epidemiología , ADN Viral/genética , Femenino , Genoma Viral/genética , Masculino , Infecciones por Parvoviridae/epidemiología , Infecciones por Parvoviridae/virología , Parvovirinae/clasificación , Filogenia , Ovinos , Enfermedades de las Ovejas/epidemiología , Proteínas Virales/genética
10.
Arch Virol ; 166(5): 1455-1462, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33704558

RESUMEN

During the dengue epidemic in Yunnan Province, China, during 2019, a concurrent outbreak of chikungunya occurred in the city of Ruili, which is located in the southwest of the province, adjacent to Myanmar. As part of this outbreak, three neonatal cases of infection with indigenous chikungunya virus from mother-to-child (vertical) transmission were observed. Isolates of chikungunya virus were obtained from 37 serum samples of patients with chikungunya during this outbreak, and a phylogenetic analysis of these isolates revealed that they belong to the Indian Ocean subclade of the East/Central/South African genotype. The E1 genes of these viruses did not harbor the A226V mutation.


Asunto(s)
Fiebre Chikungunya/virología , Virus Chikungunya/aislamiento & purificación , Enfermedades Transmisibles Emergentes/virología , Transmisión Vertical de Enfermedad Infecciosa , Fiebre Chikungunya/epidemiología , Fiebre Chikungunya/transmisión , Virus Chikungunya/clasificación , Virus Chikungunya/genética , China/epidemiología , Enfermedades Transmisibles Emergentes/epidemiología , Enfermedades Transmisibles Emergentes/transmisión , Brotes de Enfermedades , Femenino , Genoma Viral/genética , Genotipo , Humanos , Masculino , Mutación , Filogenia , ARN Viral/genética , Proteínas Virales/genética
11.
Arch Virol ; 166(5): 1355-1370, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33709216

RESUMEN

Porcine teschovirus (PTV) is a causative agent of reproductive disorders, encephalomyelitis, respiratory diseases, and diarrhea in swine, with a worldwide distribution. In this work, we identified PTV-associated nonsuppurative encephalitis as a potential cause of posterior paralysis in neonatal pigs in northeast China. Using indirect immunofluorescence assay, western blot, electron microscopy, and genome sequencing, we identified a neurotropic PTV strain, named CHN-NP1-2016, in the supernatants of pooled cerebrum and cerebellum samples from an affected piglet. Nucleotide sequence alignment revealed that the whole genome of CHN-NP1-2016 shared the highest sequence similarity (86.76% identity) with PTV 1 strain Talfan. A combination of phylogenetic and genetic divergence analysis was applied based on the deduced amino acid sequence of the P1 gene with a cutoff value of the genetic distance (0.102 ± 0.008) for defining PTV genotypes, and this showed that CHN-NP1-2016 is a variant of genotype 1. In total, 16 unique mutations and five mutant clusters were detected in the capsid proteins VP1 and VP2 of CHN-NP1-2016 when compared to other PTV1 isolates. Importantly, we detected three mutant clusters located in the exposed surface loops of the capsid protein, potentially indicating significant differences in major neutralization epitopes. Moreover, a potential recombination event in the P1 region of PTV CHN-NP1-2016 was detected. These findings provide valuable insights into the role of recombination in the evolution of teschoviruses. To our knowledge, this is the first case report of PTV-1-associated encephalitis in northeast China. Future investigations will narrow on the serology and pathogenicity of this novel isolate.


Asunto(s)
Encefalitis Viral/veterinaria , Infecciones por Picornaviridae/veterinaria , Enfermedades de los Porcinos/virología , Teschovirus/genética , Teschovirus/aislamiento & purificación , Animales , Encéfalo/virología , China/epidemiología , Encefalitis Viral/patología , Encefalitis Viral/virología , Genoma Viral/genética , Genotipo , Mutación , Filogenia , Infecciones por Picornaviridae/patología , Infecciones por Picornaviridae/virología , ARN Viral/genética , Recombinación Genética , Porcinos , Teschovirus/clasificación , Proteínas Virales/genética
13.
PLoS One ; 16(3): e0243265, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33770098

RESUMEN

Severe acute respiratory disease coronavirus 2 (SARS-CoV-2) which causes corona virus disease (COVID-19) was first identified in Wuhan, China in December 2019 and has since led to a global pandemic. Importations of SARS-CoV-2 to Israel in late February from multiple countries initiated a rapid outbreak across the country. In this study, SARS-CoV-2 whole genomes were sequenced from 59 imported samples with a recorded country of importation and 101 early circulating samples in February to mid-March 2020 and analyzed to infer clades and mutational patterns with additional sequences identified Israel available in public databases. Recorded importations in February to mid-March, mostly from Europe, led to multiple transmissions in all districts in Israel. Although all SARS-CoV-2 defined clades were imported, clade 20C became the dominating clade in the circulating samples. Identification of novel, frequently altered mutated positions correlating with clade-defining positions provide data for surveillance of this evolving pandemic and spread of specific clades of this virus. SARS-CoV-2 continues to spread and mutate in Israel and across the globe. With economy and travel resuming, surveillance of clades and accumulating mutations is crucial for understanding its evolution and spread patterns and may aid in decision making concerning public health issues.


Asunto(s)
/patología , Variación Genética , Genoma Viral/genética , /genética , /epidemiología , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Israel/epidemiología , Mutación , /aislamiento & purificación
15.
J Integr Bioinform ; 18(1): 19-26, 2021 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-33721918

RESUMEN

SARS-CoV-2 has spread worldwide and caused social, economic, and health turmoil. The first genome assembly of SARS-CoV-2 was produced in Wuhan, and it is widely used as a reference. Subsequently, more than a hundred additional SARS-CoV-2 genomes have been sequenced. While the genomes appear to be mostly identical, there are variations. Therefore, an alignment of all available genomes and the derived consensus sequence could be used as a reference, better serving the science community. Variations are significant, but representing them in a genome browser can become, especially if their sequences are largely identical. Here we summarize the variation in one track. Other information not currently found in genome browsers for SARS-CoV-2, such as predicted miRNAs and predicted TRS as well as secondary structure information, were also added as tracks to the consensus genome. We believe that a genome browser based on the consensus sequence is better suited when considering worldwide effects and can become a valuable resource in the combating of COVID-19. The genome browser is available at http://cov.iaba.online.


Asunto(s)
Genoma Viral/genética , /genética , Secuencia de Bases , Humanos , Programas Informáticos
16.
Front Cell Infect Microbiol ; 11: 609160, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33732659

RESUMEN

There is an increased global outbreak of diseases caused by coronaviruses affecting respiratory tracts of birds and mammals. Recent dangerous coronaviruses are MERS-CoV, SARS-CoV, and SARS-CoV-2, causing respiratory illness and even failure of several organs. However, profound impact of coronavirus on host cells remains elusive. In this study, we analyzed transcriptome of MERS-CoV, SARS-CoV, and SARS-CoV-2 infected human lung-derived cells, and observed that infection of these coronaviruses all induced increase of retrotransposon expression with upregulation of TET genes. Upregulation of retrotransposon was also observed in SARS-CoV-2 infected human intestinal organoids. Retrotransposon upregulation may lead to increased genome instability and enhanced expression of genes with readthrough from retrotransposons. Therefore, people with higher basal level of retrotransposon such as cancer patients and aged people may have increased risk of symptomatic infection. Additionally, we show evidence supporting long-term epigenetic inheritance of retrotransposon upregulation. We also observed chimeric transcripts of retrotransposon and SARS-CoV-2 RNA for potential human genome invasion of viral fragments, with the front and the rear part of SARS-CoV-2 genome being easier to form chimeric RNA. Thus, we suggest that primers and probes for nucleic acid detection should be designed in the middle of virus genome to identify live virus with higher probability. In summary, we propose our hypothesis that coronavirus invades human cells and interacts with retrotransposon, eliciting more severe symptoms in patients with underlying diseases. In the treatment of patients with coronavirus infection, it may be necessary to pay more attention to the potential harm contributed by retrotransposon dysregulation.


Asunto(s)
Infecciones por Coronavirus/virología , Coronavirus/genética , Genoma Viral/genética , Retroelementos/genética , Transcriptoma , Línea Celular Tumoral , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/genética , Virus del SRAS/genética , /genética
17.
Nucleic Acids Res ; 49(6): 3092-3108, 2021 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-33693814

RESUMEN

The rapid spread of COVID-19 is motivating development of antivirals targeting conserved SARS-CoV-2 molecular machinery. The SARS-CoV-2 genome includes conserved RNA elements that offer potential small-molecule drug targets, but most of their 3D structures have not been experimentally characterized. Here, we provide a compilation of chemical mapping data from our and other labs, secondary structure models, and 3D model ensembles based on Rosetta's FARFAR2 algorithm for SARS-CoV-2 RNA regions including the individual stems SL1-8 in the extended 5' UTR; the reverse complement of the 5' UTR SL1-4; the frameshift stimulating element (FSE); and the extended pseudoknot, hypervariable region, and s2m of the 3' UTR. For eleven of these elements (the stems in SL1-8, reverse complement of SL1-4, FSE, s2m and 3' UTR pseudoknot), modeling convergence supports the accuracy of predicted low energy states; subsequent cryo-EM characterization of the FSE confirms modeling accuracy. To aid efforts to discover small molecule RNA binders guided by computational models, we provide a second set of similarly prepared models for RNA riboswitches that bind small molecules. Both datasets ('FARFAR2-SARS-CoV-2', https://github.com/DasLab/FARFAR2-SARS-CoV-2; and 'FARFAR2-Apo-Riboswitch', at https://github.com/DasLab/FARFAR2-Apo-Riboswitch') include up to 400 models for each RNA element, which may facilitate drug discovery approaches targeting dynamic ensembles of RNA molecules.


Asunto(s)
Consenso , Modelos Moleculares , Conformación de Ácido Nucleico , ARN Viral/química , /genética , Regiones no Traducidas 3'/genética , Regiones no Traducidas 5'/genética , Algoritmos , Aptámeros de Nucleótidos/genética , Secuencia de Bases , Sitios de Unión , Microscopía por Crioelectrón , Conjuntos de Datos como Asunto , Evaluación Preclínica de Medicamentos/métodos , Sistema de Lectura Ribosómico/genética , Genoma Viral/genética , Estabilidad del ARN , ARN Viral/genética , Reproducibilidad de los Resultados , Riboswitch/genética , Bibliotecas de Moléculas Pequeñas/química
18.
Nat Commun ; 12(1): 1810, 2021 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-33753725

RESUMEN

For most pathogens, transmission is driven by interactions between the behaviours of infectious individuals, the behaviours of the wider population, the local environment, and immunity. Phylogeographic approaches are currently unable to disentangle the relative effects of these competing factors. We develop a spatiotemporally structured phylogenetic framework that addresses these limitations by considering individual transmission events, reconstructed across spatial scales. We apply it to geocoded dengue virus sequences from Thailand (N = 726 over 18 years). We find infected individuals spend 96% of their time in their home community compared to 76% for the susceptible population (mainly children) and 42% for adults. Dynamic pockets of local immunity make transmission more likely in places with high heterotypic immunity and less likely where high homotypic immunity exists. Age-dependent mixing of individuals and vector distributions are not important in determining spread. This approach provides previously unknown insights into one of the most complex disease systems known and will be applicable to other pathogens.


Asunto(s)
Algoritmos , Virus del Dengue/genética , Dengue/transmisión , Modelos Teóricos , Adulto , Aedes/virología , Animales , Niño , Dengue/epidemiología , Dengue/virología , Virus del Dengue/clasificación , Virus del Dengue/fisiología , Genoma Viral/genética , Interacciones Huésped-Patógeno , Humanos , Mosquitos Vectores/virología , Filogenia , Filogeografía/métodos , Filogeografía/estadística & datos numéricos , Dinámica Poblacional , Tailandia/epidemiología
19.
Hawaii J Health Soc Welf ; 80(3): 52-61, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33718878

RESUMEN

The COVID-19 pandemic has ravaged the world, caused over 1.8 million deaths in its first year, and severely affected the global economy. Hawai'i has not been spared from the transmission of SARS-CoV-2 in the local population, including high infection rates in racial and ethnic minorities. Early in the pandemic, we described in this journal various technologies used for the detection of SARS-CoV-2. Herein we characterize a 969-bp SARS-CoV-2 segment of the S gene downstream of the receptor-binding domain. At the John A. Burns School of Medicine Biocontainment Facility, RNA was extracted from an oropharyngeal swab and a nasal swab from 2 patients from Hawai'i who were infected with SARS-CoV-2 in August 2020. Following PCR, the 2 viral strains were sequenced using Sanger sequencing, and phylogenetic trees were generated using MEGAX. Phylogenetic tree results indicate that the virus has been introduced to Hawai'i from multiple sources. Further, we decoded 13 single nucleotide polymorphisms across 13 unique SARS-CoV-2 genomes within this region of the S gene, with 1 non-synonymous mutation (P681H) found in the 2 Hawai'i strains. The P681H mutation has unique and emerging characteristics with a significant exponential increase in worldwide frequency when compared to the plateauing of the now universal D614G mutation. The P681H mutation is also characteristic of the new SARS-CoV-2 variants from the United Kingdom and Nigeria. Additionally, several mutations resulting in cysteine residues were detected, potentially resulting in disruption of the disulfide bridges in and around the receptor-binding domain. Targeted sequence characterization is warranted to determine the origin of multiple introductions of SARS-CoV-2 circulating in Hawai'i.


Asunto(s)
/virología , Genoma Viral/genética , Mutación/genética , /genética , Evolución Molecular , Hawaii/epidemiología , Humanos , Filogenia , Análisis de Secuencia
20.
Arch Virol ; 166(5): 1525-1528, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33721097

RESUMEN

Here, we report the full-length genome sequence of a novel cogu-like virus identified in Brassica campestris L. ssp. Chinensis (B. campestris), an economically important vegetable in China. This virus, tentatively named "Brassica campestris chinensis coguvirus 1" (BCCoV1), has a bipartite genome that consists of two RNA molecules (RNA1 and RNA2). The negative-stranded (ns) RNA1 is 6757 nt in length, encoding the putative RNA-dependent RNA polymerase (RdRp), and the ambisense RNA2 is 3061 nt long, encoding the putative movement protein (MP) and nucleocapsid protein (NP). A homology search of the RdRp, MP, and NP showed that they are closely related to five other recently discovered negative-stranded RNA (nsRNA) viruses infecting plants, belonging to the new genus Coguvirus. Phylogenetic analysis of the 252-kDa RdRp confirmed the classification of this virus, showing that BCCoV1 possibly belongs to the genus Coguvirus, family Phenuiviridae, order Bunyavirales. The present study improves our understanding of the viral diversity in B. campestris and the evolution of nsRNA viruses.


Asunto(s)
Brassica rapa/virología , /clasificación , Secuencia de Bases , China , Genoma Viral/genética , Filogenia , Enfermedades de las Plantas/virología , ARN Viral/genética , Verduras/virología , Proteínas Virales/genética
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