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1.
Sci Adv ; 10(28): eadn3628, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38985879

RESUMO

The expression of tumor-specific antigens during cancer progression can trigger an immune response against the tumor. Here, we investigate if microproteins encoded by noncanonical open reading frames (ncORFs) are a relevant source of tumor-specific antigens. We analyze RNA sequencing data from 117 hepatocellular carcinoma (HCC) tumors and matched healthy tissue together with ribosome profiling and immunopeptidomics data. Combining human leukocyte antigen-epitope binding predictions and experimental validation experiments, we conclude that around 40% of the tumor-specific antigens in HCC are likely to be derived from ncORFs, including two peptides that can trigger an immune response in humanized mice. We identify a subset of 33 tumor-specific long noncoding RNAs expressing novel cancer antigens shared by more than 10% of the HCC samples analyzed, which, when combined, cover a large proportion of the patients. The results of the study open avenues for extending the range of anticancer vaccines.


Assuntos
Antígenos de Neoplasias , Carcinoma Hepatocelular , Neoplasias Hepáticas , Fases de Leitura Aberta , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/imunologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Animais , Camundongos , Estudos de Coortes , RNA Longo não Codificante/genética , Regulação Neoplásica da Expressão Gênica , Micropeptídeos
2.
J Med Virol ; 96(7): e29752, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38949191

RESUMO

Antiviral signaling, immune response and cell metabolism are dysregulated by SARS-CoV-2, the causative agent of COVID-19. Here, we show that SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10 induce a significant mitochondrial and metabolic reprogramming in A549 lung epithelial cells. While ORF9b, ORF9c and ORF10 induced largely overlapping transcriptomes, ORF3a induced a distinct transcriptome, including the downregulation of numerous genes with critical roles in mitochondrial function and morphology. On the other hand, all four ORFs altered mitochondrial dynamics and function, but only ORF3a and ORF9c induced a marked alteration in mitochondrial cristae structure. Genome-Scale Metabolic Models identified both metabolic flux reprogramming features both shared across all accessory proteins and specific for each accessory protein. Notably, a downregulated amino acid metabolism was observed in ORF9b, ORF9c and ORF10, while an upregulated lipid metabolism was distinctly induced by ORF3a. These findings reveal metabolic dependencies and vulnerabilities prompted by SARS-CoV-2 accessory proteins that may be exploited to identify new targets for intervention.


Assuntos
COVID-19 , Mitocôndrias , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Mitocôndrias/metabolismo , COVID-19/metabolismo , COVID-19/virologia , COVID-19/patologia , Células A549 , Proteínas Virais Reguladoras e Acessórias/metabolismo , Proteínas Virais Reguladoras e Acessórias/genética , Transcriptoma , Fases de Leitura Aberta , Proteínas Virais/genética , Proteínas Virais/metabolismo , Proteínas Viroporinas
3.
Arch Virol ; 169(8): 159, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38972922

RESUMO

In this study, we identified a novel partitivirus, named "Cordyceps militaris partitivirus 1" (CmPV1), in Cordyceps militaris strain RCEF7506. The complete genome of CmPV1 comprises two segments, dsRNA1 and dsRNA2, each encoding a single protein. dsRNA1 (2,206 bp) encodes an RNA-dependent RNA polymerase (RdRp), and dsRNA2 (2,256 bp) encodes a coat protein (CP). Sequence analysis revealed that dsRNA1 has the highest similarity to that of Bipolaris maydis partitivirus 2 (BmPV2), whereas dsRNA2 shows the highest similarity to human blood-associated partitivirus (HuBPV). Phylogenetic analysis based on RdRp sequences suggests that CmPV1 is a new member of the genus Betapartitivirus of the family Partitiviridae. This is the first documentation of a betapartitivirus infecting the entomopathogenic fungus C. militaris.


Assuntos
Cordyceps , Micovírus , Genoma Viral , Filogenia , Vírus de RNA , Cordyceps/genética , Cordyceps/virologia , Cordyceps/isolamento & purificação , Genoma Viral/genética , Micovírus/genética , Micovírus/isolamento & purificação , Micovírus/classificação , Vírus de RNA/genética , Vírus de RNA/isolamento & purificação , Vírus de RNA/classificação , RNA Viral/genética , RNA Polimerase Dependente de RNA/genética , Fases de Leitura Aberta , Proteínas Virais/genética , Proteínas do Capsídeo/genética
4.
Arch Virol ; 169(8): 165, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990253

RESUMO

Monilinia fructicola is one of the most devastating fungal diseases of rosaceous fruit crops, both in the field and postharvest, causing significant yield losses. Here, we report the discovery of a novel positive single-stranded RNA virus, Monilinia fructicola hypovirus 3 (MfHV3), in a strain (hf-1) of the phytopathogenic fungus Monilinia fructicola. The complete genome of MfHV3 is 9259 nucleotides (nt) in length and contains a single large open reading frame (ORF) from nt position 462 to 8411. This ORF encodes a polyprotein with three conserved domains, namely UDP-glycosyltransferase, RNA-dependent RNA polymerase (RdRp), and DEAD-like helicase. The MfHV3 polyprotein shares the highest similarity with Colletotrichum camelliae hypovirus 1. Phylogenetic analysis indicated that MfHV3 clustered with members of the genus Betahypovirus within the family Hypoviridae. Taken together, the results of genomic organization comparisons, amino acid sequence alignments, and phylogenetic analysis convincingly show that MfHV3 is a new member of the genus Betahypovirus, family Hypoviridae.


Assuntos
Ascomicetos , Micovírus , Genoma Viral , Fases de Leitura Aberta , Filogenia , Doenças das Plantas , Ascomicetos/virologia , Ascomicetos/genética , Micovírus/genética , Micovírus/classificação , Micovírus/isolamento & purificação , Doenças das Plantas/microbiologia , Doenças das Plantas/virologia , RNA Viral/genética , Proteínas Virais/genética , Sequenciamento Completo do Genoma , Vírus de RNA/genética , Vírus de RNA/classificação , Vírus de RNA/isolamento & purificação , RNA Polimerase Dependente de RNA/genética , Sequência de Aminoácidos
5.
Arch Virol ; 169(8): 160, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38981875

RESUMO

A novel monopartite dsRNA virus, tentatively named "sponge gourd amalgavirus 1" (SGAV1), was discovered by high-throughput sequencing in sponge gourd (Luffa cylindrica) displaying mosaic symptoms in Jiashan County, Zhejiang Province, China. The genome of SGAV1 is 3,447 nucleotides in length and contains partially overlapping open reading frames (ORFs) encoding a putative replication factory matrix-like protein and a fusion protein, respectively. The fusion protein of SGAV1 shares 57.07% identity with the homologous protein of salvia miltiorrhiza amalgavirus 1 (accession no. DAZ91057.1). Phylogenetic analysis based on the RNA-dependent RNA polymerase (RdRp) protein suggests that SGAV1 belongs to the genus Amalgavirus of the family Amalgaviridae. Moreover, analysis of SGAV1-derived small interfering RNAs indicated that SGAV1 was actively replicating in the host plant. Semi-quantitative RT-PCR showed higher levels of SGAV1 expression in leaves than in flowers and fruits. This is the first report of a novel amalgavirus found in sponge gourd in China.


Assuntos
Genoma Viral , Luffa , Fases de Leitura Aberta , Filogenia , Genoma Viral/genética , Luffa/virologia , Animais , China , Vírus de RNA de Cadeia Dupla/genética , Vírus de RNA de Cadeia Dupla/classificação , Vírus de RNA de Cadeia Dupla/isolamento & purificação , Sequenciamento Completo do Genoma , Proteínas Virais/genética , RNA Viral/genética , RNA Polimerase Dependente de RNA/genética
6.
Arch Virol ; 169(8): 161, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38981885

RESUMO

Here, we report a novel ourmia-like mycovirus, named "Phomopsis asparagi magoulivirus 1" (PaMV1), derived from the phytopathogenic fungus Phomopsis asparagi. The genome of PaMV1 consists of a positive-sense single-stranded RNA (+ ssRNA) that is 2,639 nucleotides in length, with a GC content of 57.13%. It contains a single open reading frame (ORF) encoding a putative RNA-dependent RNA polymerase (RdRp) consisting of 686 amino acids with a molecular mass of 78.57 kDa. Phylogenetic analysis based on RdRp sequences revealed that PaMV1 grouped together with Diaporthe gulyae magoulivirus 1 (DgMV1) in a distinct clade. Sequence comparisons and phylogenetic analysis suggest that PaMV1 is a novel member of the genus Magoulivirus, family Botourmiaviridae.


Assuntos
Micovírus , Genoma Viral , Fases de Leitura Aberta , Phomopsis , Filogenia , RNA Viral , Micovírus/genética , Micovírus/classificação , Micovírus/isolamento & purificação , Phomopsis/virologia , RNA Viral/genética , Sequenciamento Completo do Genoma , RNA Polimerase Dependente de RNA/genética , Composição de Bases , Doenças das Plantas/microbiologia , Doenças das Plantas/virologia , Proteínas Virais/genética , Sequência de Bases , Vírus de RNA/genética , Vírus de RNA/isolamento & purificação , Vírus de RNA/classificação
7.
Arch Virol ; 169(8): 162, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38985350

RESUMO

Using a high-throughput sequencing (HTS) approach, we report the discovery of a new alphasatellite identified in a winter barley plant collected in France in 2022 that was also infected by wheat dwarf virus (WDV). The presence of the satellite and of WDV was confirmed by several independent PCR assays, and the complete genome sequence was determined. The circular satellite genome is 1424 nt long and shows typical hallmarks of members of the subfamily Geminialphasatellitinae, including a replication-associated hairpin with a CAGTATTAC sequence and a Rep-encoding open reading frame (ORF). It also possesses a second ORF, embedded in a different frame within the Rep ORF, which is also observed in clecrusatellites and a few other members of the family Alphasatellitidae. Pairwise sequence comparisons and phylogenetic analysis showed that this satellite represents a novel species. Its closest relatives are in the genus Colecusatellite, but it likely represents a new genus given its divergence from other genera of the subfamily Geminialphasatellitinae. Given that WDV was the only virus observed in coinfection with the satellite, the name "wheat dwarf virus-associated alphasatellite" is proposed for this novel agent.


Assuntos
Genoma Viral , Hordeum , Fases de Leitura Aberta , Filogenia , Doenças das Plantas , França , Hordeum/virologia , Doenças das Plantas/virologia , Genoma Viral/genética , Geminiviridae/genética , Geminiviridae/classificação , Geminiviridae/isolamento & purificação , Vírus Satélites/genética , Vírus Satélites/classificação , Vírus Satélites/isolamento & purificação , Sequenciamento de Nucleotídeos em Larga Escala
8.
Genome Biol ; 25(1): 183, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38978079

RESUMO

BACKGROUND: Recent studies uncovered pervasive transcription and translation of thousands of noncanonical open reading frames (nORFs) outside of annotated genes. The contribution of nORFs to cellular phenotypes is difficult to infer using conventional approaches because nORFs tend to be short, of recent de novo origins, and lowly expressed. Here we develop a dedicated coexpression analysis framework that accounts for low expression to investigate the transcriptional regulation, evolution, and potential cellular roles of nORFs in Saccharomyces cerevisiae. RESULTS: Our results reveal that nORFs tend to be preferentially coexpressed with genes involved in cellular transport or homeostasis but rarely with genes involved in RNA processing. Mechanistically, we discover that young de novo nORFs located downstream of conserved genes tend to leverage their neighbors' promoters through transcription readthrough, resulting in high coexpression and high expression levels. Transcriptional piggybacking also influences the coexpression profiles of young de novo nORFs located upstream of genes, but to a lesser extent and without detectable impact on expression levels. Transcriptional piggybacking influences, but does not determine, the transcription profiles of de novo nORFs emerging nearby genes. About 40% of nORFs are not strongly coexpressed with any gene but are transcriptionally regulated nonetheless and tend to form entirely new transcription modules. We offer a web browser interface ( https://carvunislab.csb.pitt.edu/shiny/coexpression/ ) to efficiently query, visualize, and download our coexpression inferences. CONCLUSIONS: Our results suggest that nORF transcription is highly regulated. Our coexpression dataset serves as an unprecedented resource for unraveling how nORFs integrate into cellular networks, contribute to cellular phenotypes, and evolve.


Assuntos
Regulação Fúngica da Expressão Gênica , Fases de Leitura Aberta , Saccharomyces cerevisiae , Transcrição Gênica , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Evolução Molecular , Biossíntese de Proteínas
9.
Virol J ; 21(1): 153, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38972989

RESUMO

Wild waterfowl serve as a reservoir of some astroviruses. Fecal samples from wild waterfowl collected at Hong Kong's Marshes were tested using pan-astrovirus reverse transcription-PCR. Positive samples underwent subsequent host identification using DNA barcoding. Based on deduced partial sequences, noteworthy samples from three astrovirus groups (mammalian, avian and unclassified astroviruses) were further analyzed by next-generation sequencing. One sample of Avastrovirus 4 clade, MP22-196, had a nearly complete genome identified. The results of ORF2 phylogenetic analysis and genetic distance analysis indicate that Avastrovirus 4 is classified as a distinct subclade within Avastrovirus. MP22-196 has typical astrovirus genome characteristics. The unique characteristics and potential differences of this genome, compared to other avian astrovirus sequences, involve the identification of a modified sgRNA sequence situated near the ORF2 start codon, which precedes the ORF1b stop codon. Additionally, the 3' UTR of MP22-196 is shorter than other avian astroviruses. This study expands our understanding of the Avastrovirus 4 clade.


Assuntos
Infecções por Astroviridae , Aves , Fezes , Variação Genética , Genoma Viral , Filogenia , Animais , Hong Kong , Aves/virologia , Fezes/virologia , Infecções por Astroviridae/veterinária , Infecções por Astroviridae/virologia , Animais Selvagens/virologia , Doenças das Aves/virologia , Sequenciamento de Nucleotídeos em Larga Escala , Avastrovirus/genética , Avastrovirus/classificação , Avastrovirus/isolamento & purificação , RNA Viral/genética , Fases de Leitura Aberta , Astroviridae/genética , Astroviridae/isolamento & purificação , Astroviridae/classificação
10.
Int J Mol Sci ; 25(11)2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38892101

RESUMO

The central dogma treats the ribosome as a molecular machine that reads one mRNA codon at a time as it adds each amino acid to its growing peptide chain. However, this and previous studies suggest that ribosomes actually perceive pairs of adjacent codons as they take three-nucleotide steps along the mRNA. We examined GNN codons, which we find are surprisingly overrepresented in eukaryote protein-coding open reading frames (ORFs), especially immediately after NNU codons. Ribosome profiling experiments in yeast revealed that ribosomes with NNU at their aminoacyl (A) site have particularly elevated densities when NNU is immediately followed (3') by a GNN codon, indicating slower mRNA threading of the NNU codon from the ribosome's A to peptidyl (P) sites. Moreover, if the assessment was limited to ribosomes that have only recently arrived at the next codon, by examining 21-nucleotide ribosome footprints (21-nt RFPs), elevated densities were observed for multiple codon classes when followed by GNN. This striking translation slowdown at adjacent 5'-NNN GNN codon pairs is likely mediated, in part, by the ribosome's CAR surface, which acts as an extension of the A-site tRNA anticodon during ribosome translocation and interacts through hydrogen bonding and pi stacking with the GNN codon. The functional consequences of 5'-NNN GNN codon adjacency are expected to influence the evolution of protein coding sequences.


Assuntos
Códon , Fases de Leitura Aberta , Biossíntese de Proteínas , RNA Mensageiro , Ribossomos , Códon/genética , Ribossomos/metabolismo , Ribossomos/genética , Fases de Leitura Aberta/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA de Transferência/genética , RNA de Transferência/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Anticódon/genética
11.
Genome Biol Evol ; 16(7)2024 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-38934859

RESUMO

During evolution, new open reading frames (ORFs) with the potential to give rise to novel proteins continuously emerge. A recent compilation of noncanonical ORFs with translation signatures in humans has identified thousands of cases with a putative de novo origin. However, it is not known which is their distribution in the population. Are they universally translated? Here, we use ribosome profiling data from 65 lymphoblastoid cell lines from individuals of Yoruba origin to investigate this question. We identify 2,587 de novo ORFs translated in at least one of the cell lines. In line with their de novo origin, the encoded proteins tend to be smaller than 100 amino acids and encode positively charged proteins. We observe that the de novo ORFs are more polymorphic in the population than the set of canonical proteins, with a substantial fraction of them being translated in only some of the cell lines. Remarkably, this difference remains significant after controlling for differences in the translation levels. These results suggest that variations in the level translation of de novo ORFs could be a relevant source of intraspecies phenotypic diversity in humans.


Assuntos
Fases de Leitura Aberta , Polimorfismo Genético , Humanos , Biossíntese de Proteínas , Linhagem Celular , Evolução Molecular , Ribossomos/genética , Ribossomos/metabolismo
12.
Genome Biol Evol ; 16(7)2024 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-38879874

RESUMO

For protein coding genes to emerge de novo from a non-genic DNA, the DNA sequence must gain an open reading frame (ORF) and the ability to be transcribed. The newborn de novo gene can further evolve to accumulate changes in its sequence. Consequently, it can also elongate or shrink with time. Existing literature shows that older de novo genes have longer ORF, but it is not clear if they elongated with time or remained of the same length since their inception. To address this question we developed a mathematical model of ORF elongation as a Markov-jump process, and show that ORFs tend to keep their length in short evolutionary timescales. We also show that if change occurs it is likely to be a truncation. Our genomics and transcriptomics data analyses of seven Drosophila melanogaster populations are also in agreement with the model's prediction. We conclude that selection could facilitate ORF length extension that may explain why longer ORFs were observed in old de novo genes in studies analysing longer evolutionary time scales. Alternatively, shorter ORFs may be purged because they may be less likely to yield functional proteins.


Assuntos
Drosophila melanogaster , Evolução Molecular , Modelos Genéticos , Fases de Leitura Aberta , Animais , Drosophila melanogaster/genética , Cadeias de Markov
13.
Mol Biol (Mosk) ; 58(1): 54-72, 2024.
Artigo em Russo | MEDLINE | ID: mdl-38943580

RESUMO

The mobile genetic elements IS630/Tc 1/mariner (ITm) are widespread DNA transposons that make a significant contribution to the evolution of eukaryotic genomes. With the start of large-scale application of next-generation sequencing (NGS) technologies and the emergence of many new whole genome sequences of organisms in nucleotide sequence collections, the ITm elements have been identified in most taxa of the eukaryotic tree of life. Although ITm diversity has been studied in detail, new elements are still found, thus expanding the respective DNA transposon group and calling for review of its classification. Bivalve L31 elements were for the first time analyzed in detail to describe their structures, diversity, distribution, and phylogenetic position among the ITm elements. The L31 transposons were found to form an independent superfamily of an ancient origin within the ITm group. Rather high diversity was observed within the L31 clade; i.e., five phylogenetic clusters were identified. In mollusks, the L31 transposons have been detected only in the subclass Autobranchia and predominate in diversity and number in the infraclass Pteriomorphia. A protein encoded by open reading frame 2 (ORF2) was shown to be an integral structural component of almost all full-length L31 elements. The results provide for a better understanding of the evolution of particular ITm transposons. Further study of the L31 transposons in other taxa (cnidarians) and functional investigation of the ORF2 protein product will help to better understand the evolution of DNa transposons, the mechanisms of their horizontal transfer, and their contribution to eukaryotic biodiversity.


Assuntos
Bivalves , Elementos de DNA Transponíveis , Evolução Molecular , Filogenia , Animais , Elementos de DNA Transponíveis/genética , Bivalves/genética , Bivalves/classificação , Fases de Leitura Aberta
14.
Viruses ; 16(6)2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38932193

RESUMO

In the current study, a novel strain of Fusarium oxysporum alternavirus 1 (FoAV1) was identified from the Fusarium oxysporum f. sp. melonis (FOM) strain T-BJ17 and was designated as Fusarium oxysporum alternavirus 1-FOM (FoAV1-FOM). Its genome consists of four dsRNA segments of 3515 bp (dsRNA1), 2663 bp (dsRNA2), 2368 bp (dsRNA3), and 1776 bp (dsRNA4) in length. Open reading frame 1 (ORF1) in dsRNA1 was found to encode a putative RNA-dependent RNA polymerase (RdRp), whose amino acid sequence was 99.02% identical to that of its counterpart in FoAV1; while ORF2 in dsRNA2, ORF3 in dsRNA3, and ORF4 in dsRNA4 were all found to encode hypothetical proteins. Strain T-BJ17-VF, which was verified to FoAV1-FOM-free, was obtained using single-hyphal-tip culture combined with high-temperature treatment to eliminate FoAV1-FOM from strain T-BJ17. The colony growth rate, ability to produce spores, and virulence of strain T-BJ17 were significantly lower than those of T-BJ17-VF, while the dry weight of the mycelial biomass and the sensitivity to difenoconazole and pydiflumetofen of strain T-BJ17 were greater than those of T-BJ17-VF. FoAV1-FOM was capable of 100% vertical transmission via spores. To our knowledge, this is the first time that an alternavirus has infected FOM, and this is the first report of hypovirulence and increased sensitivity to difenoconazole and pydiflumetofen induced by FoAV1-FOM infection in FOM.


Assuntos
Micovírus , Fusarium , Genoma Viral , Doenças das Plantas , Triazóis , Fusarium/efeitos dos fármacos , Fusarium/genética , Fusarium/virologia , Fusarium/patogenicidade , Micovírus/genética , Micovírus/isolamento & purificação , Micovírus/classificação , Micovírus/fisiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/virologia , Triazóis/farmacologia , Dioxolanos/farmacologia , Virulência , Vírus de RNA/genética , Vírus de RNA/isolamento & purificação , Vírus de RNA/efeitos dos fármacos , Vírus de RNA/classificação , Filogenia , Fases de Leitura Aberta , Triticum/microbiologia , Triticum/virologia
15.
Viruses ; 16(6)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38932218

RESUMO

Chikungunya virus (CHIKV) is transmitted by mosquito bites and causes chikungunya fever (CHIKF). CHIKV has a single-stranded RNA genome and belongs to a single serotype with three genotypes. The Asian lineage has recently emerged in the Western Hemisphere, likely due to travel-associated introduction. Genetic variation accumulates in the CHIKV genome as the virus replicates, creating new lineages. Whole genome sequencing is ideal for studying virus evolution and spread but is expensive and complex. This study investigated whether specific, highly variable regions of the CHIKV genome could recapitulate the phylogeny obtained with a complete coding sequence (CDS). Our results revealed that concatenated highly variable regions accurately reconstructed CHIKV phylogeny, exhibiting statistically indistinguishable branch lengths and tree confidence compared to CDS. In addition, these regions adequately inferred the evolutionary relationships among CHIKV isolates from the American outbreak with similar results to the CDS. This finding suggests that highly variable regions can effectively capture the evolutionary relationships among CHIKV isolates, offering a simpler approach for future studies. This approach could be particularly valuable for large-scale surveillance efforts.


Assuntos
Febre de Chikungunya , Vírus Chikungunya , Variação Genética , Genoma Viral , Filogenia , Vírus Chikungunya/genética , Vírus Chikungunya/classificação , Vírus Chikungunya/isolamento & purificação , Febre de Chikungunya/virologia , Humanos , Genótipo , Sequenciamento Completo do Genoma/métodos , Evolução Molecular , Genômica/métodos , Fases de Leitura Aberta , Animais , RNA Viral/genética
16.
BMC Vet Res ; 20(1): 270, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38909196

RESUMO

Equid alphaherpesvirus 1 (EHV-1) is a ubiquitous and significant viral pathogen in horses worldwide, causing a range of conditions, including fever, respiratory disease, abortion in pregnant mares and the severe neurological disease called equine herpes myeloencephalopathy (EHM). Despite that EHV-1 is a notifiable animal disease in Sweden, there is limited knowledge about the circulating strains. This study aimed to analyze the genetic diversity of EHV-1 strains in equine samples from different Swedish outbreaks by partial genome sequencing. Genotyping based on three selected open reading frames ORF11, ORF30, and ORF34 in the viral genome was conducted for 55 outbreaks of EHV-1 spanning from the years 2012 to 2021. The analysis revealed 14 different genovariants, with one prominent genovariant identified in 49% of the outbreaks. Additionally, the study identified seven mutations not previously described. Three new mutations were demonstrated in ORF11, all synonymous, and four new mutations in ORF34, two synonymous, and two non-synonymous. Notably, different EHV-1 genovariants were found in five out of six studied EHM outbreaks, but clonal spreading was shown within the outbreaks. Moreover, the study demonstrated that healthy (recovered) horses that returned from an EHM outbreak at an international meeting in Valencia, Spain (2021), were positive for the virus clone responsible for the severe disease outbreak despite several weeks of quarantine. These findings shed light on the genetic diversity and transmission dynamics of the virus and significantly contribute to better understanding of the epidemiology of EHV-1 in Sweden and globally.


Assuntos
Surtos de Doenças , Variação Genética , Infecções por Herpesviridae , Herpesvirus Equídeo 1 , Doenças dos Cavalos , Animais , Cavalos , Suécia/epidemiologia , Herpesvirus Equídeo 1/genética , Herpesvirus Equídeo 1/isolamento & purificação , Doenças dos Cavalos/virologia , Doenças dos Cavalos/epidemiologia , Surtos de Doenças/veterinária , Infecções por Herpesviridae/veterinária , Infecções por Herpesviridae/epidemiologia , Infecções por Herpesviridae/virologia , Genoma Viral , Genótipo , Fases de Leitura Aberta
17.
Vet Q ; 44(1): 1-10, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38903046

RESUMO

Foot-and-mouth disease Virus (FMDV) serotype Asia1 is prevalent in the Indian subcontinent, with only G-III and G-VIII reported in India until 2020. However, in 2019, a novel genetic group within serotype Asia1, designated as G-IX, emerged in Bangladesh, followed by its detection in India in 2020. This report presents analyses of the complete coding region sequences of the G-IX lineage isolates. The length of the open reading frame (ORF) of the two G-IX isolates was 6990 nucleotides without any deletion or insertion. The G-IX isolates showed the highest sequence similarity with an isolate of G-III at the ORF, L, P2, and P3 regions, and with an isolate of G-VIII at the P1 region. Phylogenetic analysis based on the capsid region (P1) supports the hypothesis that G-VIII and G-IX originated from a common ancestor, as speculated earlier. Further, VP1 region-based phylogenetic analyses revealed the re-emergence of G-VIII after a gap of 3 years. One isolate of G-VIII collected during 2023 revealed a codon insertion in the G-H loop of VP1. The vaccine matching studies support the suitability of the currently used Indian vaccine strain IND63/1972 to contain outbreaks due to viruses belonging to G-IX.


Assuntos
Vírus da Febre Aftosa , Febre Aftosa , Filogenia , Sorogrupo , Vírus da Febre Aftosa/genética , Vírus da Febre Aftosa/classificação , Animais , Febre Aftosa/virologia , Febre Aftosa/epidemiologia , Fases de Leitura Aberta/genética , Índia/epidemiologia , Bangladesh/epidemiologia , Doenças dos Bovinos/virologia , Doenças dos Bovinos/epidemiologia , Bovinos , Antígenos Virais/genética , Proteínas do Capsídeo/genética , Genoma Viral
18.
Proc Natl Acad Sci U S A ; 121(25): e2316376121, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38861603

RESUMO

Human parainfluenza virus type 3 (HPIV3) is a major pediatric respiratory pathogen lacking available vaccines or antiviral drugs. We generated live-attenuated HPIV3 vaccine candidates by codon-pair deoptimization (CPD). HPIV3 open reading frames (ORFs) encoding the nucleoprotein (N), phosphoprotein (P), matrix (M), fusion (F), hemagglutinin-neuraminidase (HN), and polymerase (L) were modified singly or in combination to generate 12 viruses designated Min-N, Min-P, Min-M, Min-FHN, Min-L, Min-NP, Min-NPM, Min-NPL, Min-PM, Min-PFHN, Min-MFHN, and Min-PMFHN. CPD of N or L severely reduced growth in vitro and was not further evaluated. CPD of P or M was associated with increased and decreased interferon (IFN) response in vitro, respectively, but had little effect on virus replication. In Vero cells, CPD of F and HN delayed virus replication, but final titers were comparable to wild-type (wt) HPIV3. In human lung epithelial A549 cells, CPD F and HN induced a stronger IFN response, viral titers were reduced 100-fold, and the expression of F and HN proteins was significantly reduced without affecting N or P or the relative packaging of proteins into virions. Following intranasal infection in hamsters, replication in the nasal turbinates and lungs tended to be the most reduced for viruses bearing CPD F and HN, with maximum reductions of approximately 10-fold. Despite decreased in vivo replication (and lower expression of CPD F and HN in vitro), all viruses induced titers of serum HPIV3-neutralizing antibodies similar to wt and provided complete protection against HPIV3 challenge. In summary, CPD of HPIV3 yielded promising vaccine candidates suitable for further development.


Assuntos
Códon , Vírus da Parainfluenza 3 Humana , Vacinas Atenuadas , Replicação Viral , Animais , Vírus da Parainfluenza 3 Humana/imunologia , Vírus da Parainfluenza 3 Humana/genética , Humanos , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/genética , Códon/genética , Cricetinae , Infecções por Respirovirus/imunologia , Infecções por Respirovirus/prevenção & controle , Infecções por Respirovirus/virologia , Chlorocebus aethiops , Células Vero , Fases de Leitura Aberta/genética , Mesocricetus , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Vacinas Virais/imunologia , Vacinas Virais/genética , Proteínas Virais/imunologia , Proteínas Virais/genética , Vacinas contra Parainfluenza/imunologia , Vacinas contra Parainfluenza/genética
19.
J Proteomics ; 303: 105214, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38823442

RESUMO

Small ORF-encoded peptides (SEPs) are a class of low molecular weight proteins and peptides comprising <100 amino acids with important functions in various life activities. Although the sequence length is short, SEPs might also have post-translational modification (PTM). Phosphorylation is one of the most essential PTMs of proteins. In this work, we enriched phosphopeptides with IMAC and TiO2 materials and analyzed the phosphorylated SEPs in Hep3B cells. A total of 24 phosphorylated SEPs were identified, and 11 SEPs were coded by ncRNA. For the sequence analysis, we found that the general characteristics of phosphorylated SEPs are roughly the same as canonical proteins. Besides, two phosphorylation SEPs have the Stathmin family signature 2 motif, which can regulate the microtubule cytoskeleton. Some SEPs have domains or signal peptides, indicating their specific functions and subcellular locations. Kinase network analysis found a small number of kinases that may be a clue to the specific functions of some SEPs. However, only one-fifth of the predicted phosphorylation sites were identified by LC/MS/MS, indicating that many SEP PTMs are hidden in the dark, waiting to be uncovered and verified. This study helps expand our understanding of SEP and provides information for further SEP function investigation. SIGNIFICANCE: Small ORF-encoded peptides (SEPs) are important in various life activities. Although the sequence length is short (<100AA), SEPs might also have post-translational modification (PTM). Phosphorylation is one of the most essential PTMs of proteins. We enriched phosphopeptides and analyzed the phosphorylated SEPs in Hep3B cells. That is the first time to explore the PTM of SPEs systematically. Kinase network analysis found a small number of kinases that may be a clue to the specific functions of SEPs. More SEP PTMs are hidden in the dark and waiting to be uncovered and verified. This study helps expand our understanding of SEP and provides information for further SEP function investigation.


Assuntos
Processamento de Proteína Pós-Traducional , Espectrometria de Massas em Tandem , Humanos , Fosforilação , Cromatografia Líquida , Fases de Leitura Aberta , Linhagem Celular Tumoral , Fosfopeptídeos/análise , Fosfopeptídeos/metabolismo , Proteômica/métodos , Peptídeos/metabolismo , Peptídeos/química , Micropeptídeos
20.
Arch Virol ; 169(7): 141, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38850364

RESUMO

The brown planthopper (BPH), Nilaparvata lugens, is a significant agricultural pest capable of long-distance migration and transmission of viruses that cause severe disease in rice. In this study, we identified a novel segmented RNA virus in a BPH, and this virus exhibited a close relationship to members of a recently discovered virus lineage known as "quenyaviruses" within the viral kingdom Orthornavirae. This newly identified virus was named "Nilaparvata lugens quenyavirus 1" (NLQV1). NLQV1 consists of five positive-sense, single-stranded RNAs, with each segment containing a single open reading frame (ORF). The genomic characteristics and phylogenetic analysis support the classification of NLQV1 as a novel quenyavirus. Notably, all of the genome segments of NLRV contained the 5'-terminal sequence AUCUG. The characteristic virus-derived small interfering RNA (vsiRNA) profile of NLQV1 suggests that the antiviral RNAi pathway of the host BPH was activated in response to virus infection. These findings represent the first documented report of quenyaviruses in planthoppers, contributing to our understanding of quenyaviruses and expanding our knowledge of insect-specific viruses in planthoppers.


Assuntos
Genoma Viral , Hemípteros , Fases de Leitura Aberta , Filogenia , Vírus de RNA , RNA Viral , Animais , Hemípteros/virologia , Genoma Viral/genética , RNA Viral/genética , Vírus de RNA/genética , Vírus de RNA/classificação , Vírus de RNA/isolamento & purificação , Doenças das Plantas/virologia , Oryza/virologia , Sequenciamento Completo do Genoma , RNA Interferente Pequeno/genética
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