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1.
J Immunol ; 207(11): 2699-2709, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34750204

RESUMO

IFN-γ-inducible protein 16 (IFI16) recognizes viral DNAs from both nucleus-replicating viruses and cytoplasm-replicating viruses. Isoform 2 of IFI16 (IFI16-iso2) with nuclear localization sequence (NLS) has been studied extensively as a well-known DNA sensor. However, the characteristics and functions of other IFI16 isoforms are almost unknown. Here, we find that IFI16-iso1, with exactly the same length as IFI16-iso2, lacks the NLS and locates in the cytoplasm. To distinguish the functions of IFI16-iso1 and IFI16-iso2, we have developed novel nuclear viral DNA mimics that can be recognized by the nuclear DNA sensors, including IFI16-iso2 and hnRNPA2B1. The hexanucleotide motif 5'-AGTGTT-3' DNA form of the nuclear localization sequence (DNLS) effectively drives cytoplasmic viral DNA nuclear translocation. These nuclear viral DNA mimics potently induce IFN-ß and antiviral IFN-stimulated genes in human A549 cells, HEK293T cells, and mouse macrophages. The subcellular location difference of IFI16 isoforms determines their differential functions in recognizing viral DNA and activating type I IFN-dependent antiviral immunity. IFI16-iso1 preferentially colocalizes with cytoplasmic HSV60mer and cytoplasm-replicating vaccinia virus (VACV), whereas IFI16-iso2 mainly colocalizes with nuclear HSV60-DNLS and nucleus-replicating HSV-1. Compared with IFI16-iso2, IFI16-iso1 induces more transcription of IFN-ß and IFN-stimulated genes, as well as stronger antiviral immunity upon HSV60mer transfection or VACV infection. IFI16-iso2, with the ability of nuclear-cytoplasmic shuttling, clears both invaded HSV type 1 and VACV significantly. However, IFI16-iso2 induces more type I IFN-dependent antiviral immunity than IFI16-iso1 upon HSV60-DNLS transfection or HSV type 1 infection. Our study has developed potent agonists for nuclear DNA sensors and also has demonstrated that IFI16 isoforms with cytoplasmic and nuclear locations play differential roles in innate immunity against DNA viruses.


Assuntos
Núcleo Celular/imunologia , Vírus de DNA/imunologia , Proteínas Nucleares/imunologia , Fosfoproteínas/imunologia , Células Cultivadas , Humanos , Isoformas de Proteínas/imunologia
2.
Enzymes ; 49: 83-113, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34696840

RESUMO

DNA and RNA viruses depend on one or more enzymes to copy and transcribe their genome, such as a polymerase, helicase, or exonuclease. Because of the important role of these enzymes in the virus replication cycle, they are key targets for antiviral development. To better understand the function of these enzymes and their interactions with host and viral factors, biochemical, structural and single-molecule approaches have been used to study them. Each of these techniques has its own strengths, and single-molecule methods have proved particularly powerful in providing insight into the step-sizes of motor proteins, heterogeneity of enzymatic activities, transient conformational changes, and force-sensitivity of reactions. Here we will discuss how single-molecule FRET, magnetic tweezers, optical tweezers, atomic force microscopy and flow stretching approaches have revealed novel insights into polymerase fidelity, the mechanism of action of antivirals, and the protein choreography within replication complexes.


Assuntos
Vírus de DNA , Vírus de RNA , Replicação Viral , Antivirais , DNA Helicases , Vírus de DNA/enzimologia , Vírus de DNA/fisiologia , Pinças Ópticas , Vírus de RNA/enzimologia , Vírus de RNA/fisiologia
3.
PLoS One ; 16(10): e0252696, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34673785

RESUMO

Genetic and molecular modifications of the large dsDNA chloroviruses, with genomes of 290 to 370 kb, would expedite studies to elucidate the functions of both identified and unidentified virus-encoded proteins. These plaque-forming viruses replicate in certain unicellular, eukaryotic chlorella-like green algae. However, to date, only a few of these algal species and virtually none of their viruses have been genetically manipulated due to lack of practical methods for genetic transformation and genome editing. Attempts at using Agrobacterium-mediated transfection of chlorovirus host Chlorella variabilis NC64A with a specially-designed binary vector resulted in successful transgenic cell selection based on expression of a hygromycin-resistance gene, initial expression of a green fluorescence gene and demonstration of integration of Agrobacterium T-DNA. However, expression of the integrated genes was soon lost. To develop gene editing tools for modifying specific chlorovirus CA-4B genes using preassembled Cas9 protein-sgRNA ribonucleoproteins (RNPs), we tested multiple methods for delivery of Cas9/sgRNA RNP complexes into infected cells including cell wall-degrading enzymes, electroporation, silicon carbide (SiC) whiskers, and cell-penetrating peptides (CPPs). In one experiment two independent virus mutants were isolated from macerozyme-treated NC64A cells incubated with Cas9/sgRNA RNPs targeting virus CA-4B-encoded gene 034r, which encodes a glycosyltransferase. Analysis of DNA sequences from the two mutant viruses showed highly targeted nucleotide sequence modifications in the 034r gene of each virus that were fully consistent with Cas9/RNP-directed gene editing. However, in ten subsequent experiments, we were unable to duplicate these results and therefore unable to achieve a reliable system to genetically edit chloroviruses. Nonetheless, these observations provide strong initial suggestions that Cas9/RNPs may function to promote editing of the chlorovirus genome, and that further experimentation is warranted and worthwhile.


Assuntos
Proteína 9 Associada à CRISPR/genética , Sistemas CRISPR-Cas/genética , Phycodnaviridae/genética , Transformação Genética/genética , Agrobacterium/virologia , Chlorella/virologia , Vírus de DNA/genética , Eletroporação/métodos , Edição de Genes/métodos , Ribonucleoproteínas/genética , Proteínas Virais/genética
4.
J Gen Virol ; 102(10)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34714225

RESUMO

Calf diarrhoea has been a major cause of economic losses in the global dairy industry. Many factors, including multiple pathogen infections, can directly or indirectly cause calf diarrhoea. This study compared the faecal virome between 15 healthy calves and 15 calves with diarrhoea. Significantly lower diversity of viruses was found in samples from animals with diarrhoea than those in the healthy ones, and this feature may also be related to the age of the calves. Viruses belonging to the families Astroviridae and Caliciviridae that may cause diarrhoea in dairy calves have been characterized, which revealed that reads of caliciviruses and astroviruses in diarrhoea calves were much higher than those in healthy calves. Five complete genomic sequences closely related to Smacoviridae have been identified, which may participate in the regulation of the gut virus community ecology of healthy hosts together with bacteriophages. This research provides a theoretical basis for further understanding of known or potential enteric pathogens related to calf diarrhoea.


Assuntos
Doenças dos Bovinos/virologia , Bovinos/virologia , Diarreia/veterinária , Intestinos/virologia , Viroma , Animais , Caliciviridae/classificação , Caliciviridae/genética , Caliciviridae/isolamento & purificação , Vírus de DNA/classificação , Vírus de DNA/genética , Vírus de DNA/isolamento & purificação , Indústria de Laticínios , Diarreia/virologia , Fezes/virologia , Genoma Viral , Mamastrovirus/classificação , Mamastrovirus/genética , Mamastrovirus/isolamento & purificação , Metagenômica , Filogenia
5.
Arch Virol ; 166(11): 3245-3253, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34546431

RESUMO

The family Smacoviridae (order Cremevirales, class Arfiviricetes, phylum Cressdnaviricota) is comprised of viruses with small circular single-stranded DNA genomes of ~2.3-3 kb in length that have primarily been identified in fecal sample of various animals. Smacovirus genomes carry two genes in ambisense orientation encoding a capsid protein and a rolling-circle replication initiation protein, respectively. We have revised the taxonomy of the family by assigning 138 new genomic sequences deposited in GenBank to already established taxa as well as 41 new species and six new genera. Furthermore, we have adopted binomial species nomenclature, conforming to the "Genus + freeform epithet" format for all 84 species from 12 genera. The updated Smacoviridae taxonomy presented in this article has been ratified by the International Committee on Taxonomy of Viruses (ICTV).


Assuntos
Vírus de DNA/classificação , Filogenia , Animais , Vírus de DNA/genética , Fezes/virologia , Genoma Viral
6.
Int J Mol Sci ; 22(17)2021 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-34502274

RESUMO

Heat shock proteins (HSPs) are a large group of chaperones found in most eukaryotes and bacteria. They are responsible for the correct protein folding, protection of the cell against stressors, presenting immune and inflammatory cytokines; furthermore, they are important factors in regulating cell differentiation, survival and death. Although the biological function of HSPs is to maintain cell homeostasis, some of them can be used by viruses both to fold their proteins and increase the chances of survival in unfavorable host conditions. Folding viral proteins as well as replicating many different viruses are carried out by, among others, proteins from the HSP70 and HSP90 families. In some cases, the HSP70 family proteins directly interact with viral polymerase to enhance viral replication or they can facilitate the formation of a viral replication complex and/or maintain the stability of complex proteins. It is known that HSP90 is important for the expression of viral genes at both the transcriptional and the translational levels. Both of these HSPs can form a complex with HSP90 and, consequently, facilitate the entry of the virus into the cell. Current studies have shown the biological significance of HSPs in the course of infection SARS-CoV-2. A comprehensive understanding of chaperone use during viral infection will provide new insight into viral replication mechanisms and therapeutic potential. The aim of this study is to describe the molecular basis of HSP70 and HSP90 participation in some viral infections and the potential use of these proteins in antiviral therapy.


Assuntos
Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Viroses/patologia , COVID-19/metabolismo , COVID-19/patologia , COVID-19/virologia , Vírus de DNA/fisiologia , Humanos , Isoformas de Proteínas/metabolismo , Vírus de RNA/fisiologia , SARS-CoV-2/isolamento & purificação , Viroses/metabolismo , Viroses/virologia
7.
Int J Mol Sci ; 22(18)2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34575975

RESUMO

Several classes of immunomodulators are used for treating relapsing-remitting multiple sclerosis (RRMS). Most of these disease-modifying therapies, except teriflunomide, carry the risk of progressive multifocal leukoencephalopathy (PML), a severely debilitating, often fatal virus-induced demyelinating disease. Because teriflunomide has been shown to have antiviral activity against DNA viruses, we investigated whether treatment of cells with teriflunomide inhibits infection and spread of JC polyomavirus (JCPyV), the causative agent of PML. Treatment of choroid plexus epithelial cells and astrocytes with teriflunomide reduced JCPyV infection and spread. We also used droplet digital PCR to quantify JCPyV DNA associated with extracellular vesicles isolated from RRMS patients. We detected JCPyV DNA in all patients with confirmed PML diagnosis (n = 2), and in six natalizumab-treated (n = 12), two teriflunomide-treated (n = 7), and two nonimmunomodulated (n = 2) patients. Of the 21 patients, 12 (57%) had detectable JCPyV in either plasma or serum. CSF was uniformly negative for JCPyV. Isolation of extracellular vesicles did not increase the level of detection of JCPyV DNA versus bulk unprocessed biofluid. Overall, our study demonstrated an effect of teriflunomide inhibiting JCPyV infection and spread in glial and choroid plexus epithelial cells. Larger studies using patient samples are needed to correlate these in vitro findings with patient data.


Assuntos
Crotonatos/farmacologia , Vírus de DNA/efeitos dos fármacos , Hidroxibutiratos/farmacologia , Leucoencefalopatia Multifocal Progressiva/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Neuroglia/efeitos dos fármacos , Nitrilas/farmacologia , Toluidinas/farmacologia , Astrócitos/efeitos dos fármacos , Astrócitos/virologia , Linhagem Celular , Plexo Corióideo/efeitos dos fármacos , Plexo Corióideo/virologia , Vírus de DNA/patogenicidade , Doenças Desmielinizantes/tratamento farmacológico , Doenças Desmielinizantes/patologia , Doenças Desmielinizantes/virologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/virologia , Vesículas Extracelulares/efeitos dos fármacos , Vesículas Extracelulares/virologia , Humanos , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Vírus JC/efeitos dos fármacos , Vírus JC/patogenicidade , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Leucoencefalopatia Multifocal Progressiva/patologia , Leucoencefalopatia Multifocal Progressiva/virologia , Esclerose Múltipla Recidivante-Remitente/genética , Esclerose Múltipla Recidivante-Remitente/patologia , Esclerose Múltipla Recidivante-Remitente/virologia , Neuroglia/virologia , Viroses/tratamento farmacológico , Viroses/genética , Viroses/virologia
8.
Braz J Microbiol ; 52(4): 2475-2482, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34562234

RESUMO

Bufotenine, an alkaloid that can be found in plant extracts and skin secretions of amphibians, is reported to have potential antiviral activity. The present study evaluated the antiviral activity of bufotenine against different genetic lineages of rabies virus (RABV, a single-stranded, negative-sense RNA virus), canine coronavirus (CCoV, a positive-sense RNA virus) and two double-stranded DNA viruses (two strains of herpes simplex virus type 1/HSV-1 [KOS and the acyclovir-resistant HSV-1 strain 29R] and canine adenovirus 2, CAV-2). The maximal non-toxic bufotenine concentrations in Vero and BHK-21 cells were determined by MTT assays. The antiviral activity of bufotenine against each virus was assessed by examination of reductions in infectious virus titres and plaque assays. All experiments were performed with and without bufotenine, and the results were compared. Bufotenine demonstrated significant RABV inhibitory activity. No antiviral action was observed against CCoV, CAV-2 or HSV-1. These findings indicate that the antiviral activity of bufotenine is somewhat linked to the particular infectious dose used and the genetic lineage of the virus, although the mechanisms of its effects remain undetermined.


Assuntos
Antivirais , Bufotenina , Vírus de DNA/efeitos dos fármacos , Vírus de RNA/efeitos dos fármacos , Animais , Antivirais/farmacologia , Bufotenina/farmacologia , Chlorocebus aethiops , Cricetinae , Células Vero
9.
Sci Rep ; 11(1): 17758, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493784

RESUMO

DNA viruses can exploit host cellular epigenetic processes to their advantage; however, the epigenome status of most DNA viruses remains undetermined. Third generation sequencing technologies allow for the identification of modified nucleotides from sequencing experiments without specialized sample preparation, permitting the detection of non-canonical epigenetic modifications that may distinguish viral nucleic acid from that of their host, thus identifying attractive targets for advanced therapeutics and diagnostics. We present a novel nanopore de novo assembly pipeline used to assemble a misidentified Camelpox vaccine. Two confirmed deletions of this vaccine strain in comparison to the closely related Vaccinia virus strain modified vaccinia Ankara make it one of the smallest non-vector derived orthopoxvirus genomes to be reported. Annotation of the assembly revealed a previously unreported signal peptide at the start of protein A38 and several predicted signal peptides that were found to differ from those previously described. Putative epigenetic modifications around various motifs have been identified and the assembly confirmed previous work showing the vaccine genome to most closely resemble that of Vaccinia virus strain Modified Vaccinia Ankara. The pipeline may be used for other DNA viruses, increasing the understanding of DNA virus evolution, virulence, host preference, and epigenomics.


Assuntos
Vírus Defeituosos/genética , Epigenoma , Genoma Viral , Sequenciamento por Nanoporos , Orthopoxvirus/genética , Sinais Direcionadores de Proteínas/genética , Análise de Sequência de DNA/métodos , Vírus Vaccinia/genética , Proteínas Virais/genética , Vacinas Virais , Motivos de Aminoácidos , Sequência de Aminoácidos , Vírus de DNA/genética , Anotação de Sequência Molecular , Orthopoxvirus/imunologia , Deleção de Sequência , Software , Especificidade da Espécie , Emirados Árabes Unidos , Vacinas Atenuadas
10.
Nat Commun ; 12(1): 4748, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362927

RESUMO

Encapsulins are a class of microbial protein compartments defined by the viral HK97-fold of their capsid protein, self-assembly into icosahedral shells, and dedicated cargo loading mechanism for sequestering specific enzymes. Encapsulins are often misannotated and traditional sequence-based searches yield many false positive hits in the form of phage capsids. Here, we develop an integrated search strategy to carry out a large-scale computational analysis of prokaryotic genomes with the goal of discovering an exhaustive and curated set of all HK97-fold encapsulin-like systems. We find over 6,000 encapsulin-like systems in 31 bacterial and four archaeal phyla, including two novel encapsulin families. We formulate hypotheses about their potential biological functions and biomedical relevance, which range from natural product biosynthesis and stress resistance to carbon metabolism and anaerobic hydrogen production. An evolutionary analysis of encapsulins and related HK97-type virus families shows that they share a common ancestor, and we conclude that encapsulins likely evolved from HK97-type bacteriophages.


Assuntos
Bacteriófagos/metabolismo , Capsídeo/metabolismo , Células Procarióticas/metabolismo , Células Procarióticas/virologia , Archaea/metabolismo , Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Bacteriófagos/genética , Evolução Biológica , Vias Biossintéticas/genética , Proteínas do Capsídeo/química , Proteínas do Capsídeo/metabolismo , Vírus de DNA/metabolismo , Filogenia , Virulência
11.
Viruses ; 13(7)2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34372550

RESUMO

Persistent hepatitis B virus (HBV) infection remains a serious medical problem worldwide, with an estimated global burden of 257 million carriers. Prophylactic and therapeutic interventions, in the form of a vaccine, immunomodulators, and nucleotide and nucleoside analogs, are available. Vaccination, however, offers no therapeutic benefit to chronic sufferers and has had a limited impact on infection rates. Although immunomodulators and nucleotide and nucleoside analogs have been licensed for treatment of chronic HBV, cure rates remain low. Transcription activator-like effector nucleases (TALENs) designed to bind and cleave viral DNA offer a novel therapeutic approach. Importantly, TALENs can target covalently closed circular DNA (cccDNA) directly with the potential of permanently disabling this important viral replicative intermediate. Potential off-target cleavage by engineered nucleases leading to toxicity presents a limitation of this technology. To address this, in the context of HBV gene therapy, existing TALENs targeting the viral core and surface open reading frames were modified with second- and third-generation FokI nuclease domains. As obligate heterodimers these TALENs prevent target cleavage as a result of FokI homodimerization. Second-generation obligate heterodimeric TALENs were as effective at silencing viral gene expression as first-generation counterparts and demonstrated an improved specificity in a mouse model of HBV replication.


Assuntos
Vírus da Hepatite B/genética , Hepatite B/tratamento farmacológico , Nucleases dos Efetores Semelhantes a Ativadores de Transcrição/genética , Animais , Animais não Endogâmicos , Antivirais/uso terapêutico , Linhagem Celular , Vírus de DNA/genética , DNA Circular , DNA Viral/genética , Desoxirribonucleases de Sítio Específico do Tipo II/genética , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Modelos Animais de Doenças , Endonucleases/genética , Feminino , Terapia Genética/métodos , Células HEK293 , Células Hep G2 , Hepatite B/genética , Hepatite B/imunologia , Hepatite B Crônica/genética , Hepatite B Crônica/virologia , Humanos , Camundongos , Nucleases dos Efetores Semelhantes a Ativadores de Transcrição/uso terapêutico , Replicação Viral/genética
12.
Sci Rep ; 11(1): 16402, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385487

RESUMO

Ascoviruses are large dsDNA viruses characterized by the extraordinary changes they induce in cellular pathogenesis and architecture whereby after nuclear lysis and extensive hypertrophy, each cell is cleaved into numerous vesicles for virion reproduction. However, the level of viral replication and transcription in vesicles compared to other host tissues remains uncertain. Therefore, we applied RNA-Sequencing to compare the temporal transcriptome of Spodoptera frugiperda ascovirus (SfAV) and Trichoplusia ni ascovirus (TnAV) at 7, 14, and 21 days post-infection (dpi). We found most transcription occurred in viral vesicles, not in initial tissues infected, a remarkably novel reproduction mechanism compared to all other viruses and most other intracellular pathogens. Specifically, the highest level of viral gene expression occurred in hemolymph, for TnAV at 7 dpi, and SfAV at 14 dpi. Moreover, we found that host immune genes were partially down-regulated in hemolymph, where most viral replication occurred in highly dense accumulations of vesicles.


Assuntos
Ascoviridae/genética , Hemolinfa/virologia , Transcriptoma/genética , Tropismo/genética , Animais , Vírus de DNA/genética , DNA Viral/genética , Genoma Viral/genética , Fases de Leitura Aberta/genética , Reprodução/genética , Análise de Sequência de DNA/métodos , Spodoptera/genética , Vírion/genética , Replicação Viral/genética
13.
Adv Virus Res ; 110: 1-26, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34353480

RESUMO

Over the last two decades, the viromes of our closest relatives, the African great apes (AGA), have been intensively studied. Comparative approaches have unveiled diverse evolutionary patterns, highlighting both stable host-virus associations over extended evolutionary timescales and much more recent viral emergence events. In this chapter, we summarize these findings and outline how they have shed a new light on the origins and evolution of many human-infecting viruses. We also show how this knowledge can be used to better understand the evolution of human health in relation to viral infections.


Assuntos
Hominidae , Viroses , Vírus , Animais , Evolução Biológica , Vírus de DNA , Humanos , Viroses/veterinária , Vírus/genética
14.
PLoS One ; 16(8): e0255425, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34383794

RESUMO

Canine bocaviruses (CBoVs) have been recognized as pathogens associated with intestinal diseases. Hematogenous spreading caused by CBoV has been documented and may potentiate the virus entry across the blood-brain barrier to initiate a brain infection. This study focused attention on CBoV detection in cases of encepahlopathy and attempted to determine its viral localization. A total of 107 dog brains that histologically exhibited encephalopathy (ED) were investigated for the presence of CBoVs using polymerase chain reaction (PCR). Thirty-three histologically normal brain samples from dogs were used as a control group (CD). CBoV-2 was detected in 15 ED dogs (14.02%) but not in CD dogs (p = 0.02), while no CBoV-1 and -3 were detected. Among the CBoV-2 positive dogs, brain histological changes were characterized by nonsuppurative encephalitis, with inclusion body-like materials in some brains. In situ hybridization (ISH) and transmission electron microscopy (TEM) confirmed the presence of CBoV-2 viral particles in glial cells, supporting neurotropism of this virus. ISH signals were also detected in the intestines, lymphoid organs, and the heart, suggesting both enteral and parenteral infections of this virus. Whole genome characterization and evolutionary analysis revealed genetic diversity of CBoV-2 sequences and it was varying among the different countries where the virus was detected. This study points to a possible association of CBoV-2 with encephalopathy in dogs. It also highlights the genetic diversity and cellular tropism of this virus.


Assuntos
Bocavirus , Animais , Vírus de DNA , Doenças do Cão , Cães , Infecções por Parvoviridae , Filogenia , Análise de Sequência de DNA
15.
Viruses ; 13(7)2021 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-34199077

RESUMO

Many viruses, especially RNA viruses, utilize programmed ribosomal frameshifting and/or stop codon readthrough in their expression, and in the decoding of a few a UGA is dynamically redefined to specify selenocysteine. This recoding can effectively increase viral coding capacity and generate a set ratio of products with the same N-terminal domain(s) but different C-terminal domains. Recoding can also be regulatory or generate a product with the non-universal 21st directly encoded amino acid. Selection for translation speed in the expression of many viruses at the expense of fidelity creates host immune defensive opportunities. In contrast to host opportunism, certain viruses, including some persistent viruses, utilize recoding or adventitious frameshifting as part of their strategy to evade an immune response or specific drugs. Several instances of recoding in small intensively studied viruses escaped detection for many years and their identification resolved dilemmas. The fundamental importance of ribosome ratcheting is consistent with the initial strong view of invariant triplet decoding which however did not foresee the possibility of transitory anticodon:codon dissociation. Deep level dynamics and structural understanding of recoding is underway, and a high level structure relevant to the frameshifting required for expression of the SARS CoV-2 genome has just been determined.


Assuntos
Vírus de DNA/genética , Vírus de DNA/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Evasão da Resposta Imune , Vírus de RNA/genética , Antivirais/farmacologia , Códon de Terminação , Vírus de DNA/efeitos dos fármacos , Mudança da Fase de Leitura do Gene Ribossômico , Antígenos de Histocompatibilidade Classe I/genética , Conformação de Ácido Nucleico , Peptídeos/imunologia , Biossíntese de Proteínas , Vírus de RNA/efeitos dos fármacos , Vírus de RNA/imunologia
16.
Viruses ; 13(6)2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200389

RESUMO

Isolation and characterization of circular replicase-encoding single-stranded (ss) DNA from animal, plant and environmental samples are rapidly evolving in virology. We detected 21 circular DNA elements, including one genomoviral sequence, in individual milk samples from domesticated Asian water buffaloes (Bubalus arnee f. bubalis). Most of the obtained genomes are related to Sphinx 1.76 and Sphinx 2.36 sequences and share a high degree of similarity to recently published circular DNAs-named BMMF (bovine meat and milk factors)-that have been isolated from commercial milk, as well as from bovine serum. Characteristic features such as rep genes, tandem repeats and inverted repeats were detected. These BMMF have recently been found to be present in taurine-type dairy cattle breeds descending from the aurochs (Bos primigenius). Importantly, the occurrence of BMMF has been linked to the higher incidence of colorectal and breast cancer in North America and Western Europe compared with Asia. This is the first report of circular ssDNA detected in milk from the domesticated form of the wild Asian water buffalo (B. arnee) belonging to the subfamily Bovinae. This novelty should be taken into account in view of the above-mentioned cancer hypothesis.


Assuntos
Búfalos/genética , DNA Circular , DNA de Cadeia Simples , Leite , Animais , Sequência de Bases , Biomarcadores , Bovinos , Clonagem Molecular , Vírus de DNA/genética , Leite/química , Filogenia , Reação em Cadeia da Polimerase , Análise de Sequência de DNA
17.
Int J Mol Sci ; 22(12)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201359

RESUMO

Red pepper (Capsicum annuum, L.), is one of the most important spice plants in Korea. Overwintering pepper fruits are a reservoir of various microbial pepper diseases. Here, we conducted metagenomics (DNA sequencing) and metatranscriptomics (RNA sequencing) using samples collected from three different fields. We compared two different library types and three different analytical methods for the identification of microbiomes in overwintering pepper fruits. Our results demonstrated that DNA sequencing might be useful for the identification of bacteria and DNA viruses such as bacteriophages, while mRNA sequencing might be beneficial for the identification of fungi and RNA viruses. Among three analytical methods, KRAKEN2 with raw data reads (KRAKEN2_R) might be superior for the identification of microbial species to other analytical methods. However, some microbial species with a low number of reads were wrongly assigned at the species level by KRAKEN2_R. Moreover, we found that the databases for bacteria and viruses were better established as compared to the fungal database with limited genome data. In summary, we carefully suggest that different library types and analytical methods with proper databases should be applied for the purpose of microbiome study.


Assuntos
Bactérias/genética , Capsicum/genética , Vírus de DNA/genética , Frutas/crescimento & desenvolvimento , Metagenoma , Vírus de RNA/genética , Transcriptoma , Bactérias/classificação , Capsicum/microbiologia , Capsicum/virologia , Vírus de DNA/classificação , Frutas/microbiologia , Frutas/virologia , Vírus de RNA/classificação , Estações do Ano
18.
J Gen Virol ; 102(7)2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34328827

RESUMO

Members of the family Thaspiviridae have linear dsDNA genomes of 27 to 29 kbp and are the first viruses known to infect mesophilic ammonia-oxidizing archaea of the phylum Thaumarchaeota. The spindle-shaped virions of Nitrosopumilus spindle-shaped virus 1 possess short tails at one pole and measure 64±3 nm in diameter and 112±6 nm in length. This morphology is similar to that of members of the families Fuselloviridae and Halspiviridae. Virus replication is not lytic but leads to growth inhibition of the host. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Thaspiviridae, which is available at ictv.global/report/thaspiviridae.


Assuntos
Archaea/virologia , Vírus de Archaea/classificação , Vírus de DNA/classificação , Vírus de Archaea/genética , Vírus de Archaea/fisiologia , Vírus de Archaea/ultraestrutura , Vírus de DNA/genética , Vírus de DNA/fisiologia , Vírus de DNA/ultraestrutura , Genoma Viral , Especificidade de Hospedeiro , Vírion/ultraestrutura , Replicação Viral
20.
Arch Virol ; 166(10): 2911-2926, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34331585

RESUMO

The family Genomoviridae (phylum Cressdnaviricota, class Repensiviricetes, order Geplafuvirales) includes viruses with circular single-stranded DNA genomes encoding two proteins, the capsid protein and the rolling-circle replication initiation protein. The genomes of the vast majority of members in this family have been sequenced directly from diverse environmental or animal- and plant-associated samples, but two genomoviruses have been identified infecting fungi. Since the last taxonomic update of the Genomoviridae, a number of new members of this family have been sequenced. Here, we report on the most recent taxonomic update, including the creation of one new genus, Gemytripvirus, and classification of ~420 new genomoviruses into 164 new species. We also announce the adoption of the "Genus + freeform epithet" binomial system for the naming of all 236 officially recognized species in the family Genomoviridae. The updated taxonomy presented in this article has been accepted by the International Committee on Taxonomy of Viruses (ICTV).


Assuntos
Vírus de DNA/classificação , Animais , Sequência de Bases , Vírus de DNA/genética , Vírus de DNA/fisiologia , DNA Circular , DNA de Cadeia Simples , Genoma Viral/genética , Especificidade de Hospedeiro , Filogenia , Terminologia como Assunto , Proteínas Virais/genética
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