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1.
Viruses ; 16(1)2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38257787

RESUMO

The introduction of three single nucleotide mutations into the genome of the virulent RVFV ZH548 strain allows for the rescue of a fully attenuated virus in mice (ZH548-rA2). These mutations are located in the viral genes encoding the RdRp and the non-structural protein NSs. This paper shows the results obtained after the subcutaneous inoculation of ZH548-rA2 in adult sheep and the subsequent challenge with the parental virus (ZH548-rC1). Inoculation with the ZH548-rA2 virus caused no detectable clinical or pathological effect in sheep, whereas inoculation of the parental rC1 virus caused lesions compatible with viral infection characterised by the presence of scattered hepatic necrosis. Viral infection was confirmed via immunohistochemistry, with hepatocytes within the necrotic foci appearing as the main cells immunolabelled against viral antigen. Furthermore, the inoculation of sheep with the rA2 virus prevented the liver damage expected after rC1 virus inoculation, suggesting a protective efficacy in sheep which correlated with the induction of both humoral and cell-mediated immune responses.


Assuntos
Vírus da Febre do Vale do Rift , Viroses , Animais , Camundongos , Ovinos , Vírus da Febre do Vale do Rift/genética , Antígenos Virais , Genes Virais , Hepatócitos
2.
PLoS Pathog ; 20(1): e1011941, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38215155

RESUMO

Tomato yellow leaf curl virus (TYLCV, genus Begomovirus, family Geminiviridae) causes severe disease of cultivated tomatoes. Geminiviruses replicate circular single-stranded genomic DNA via rolling-circle and recombination-dependent mechanisms, frequently generating recombinants in mixed infections. Circular double-stranded intermediates of replication also serve as templates for Pol II bidirectional transcription. IS76, a recombinant derivative of TYLCV with a short sequence in the bidirectional promoter/origin-of-replication region acquired from a related begomovirus, outcompetes TYLCV in mixed infection and breaks disease resistance in tomato Ty-1 cultivars. Ty-1 encodes a γ-clade RNA-dependent RNA polymerase (RDRγ) implicated in Dicer-like (DCL)-mediated biogenesis of small interfering (si)RNAs directing gene silencing. Here, we profiled transcriptome and small RNAome of Ty-1 resistant and control susceptible plants infected with TYLCV, IS76 or their combination at early and late infection stages. We found that RDRγ boosts production rates of 21, 22 and 24 nt siRNAs from entire genomes of both viruses and modulates DCL activities in favour of 22 and 24 nt siRNAs. Compared to parental TYLCV, IS76 undergoes faster transition to the infection stage favouring rightward transcription of silencing suppressor and coat protein genes, thereby evading RDRγ activity and facilitating its DNA accumulation in both single and mixed infections. In coinfected Ty-1 plants, IS76 efficiently competes for host replication and transcription machineries, thereby impairing TYLCV replication and transcription and forcing its elimination associated with further increased siRNA production. RDRγ is constitutively overexpressed in Ty-1 plants, which correlates with begomovirus resistance, while siRNA-generating DCLs (DCL2b/d, DCL3, DCL4) and genes implicated in siRNA amplification (α-clade RDR1) and function (Argonaute2) are upregulated to similar levels in TYLCV- and IS76-infected susceptible plants. Collectively, IS76 recombination facilitates replication and promotes expression of silencing suppressor and coat proteins, which allows the recombinant virus to evade the negative impact of RDRγ-boosted production of viral siRNAs directing transcriptional and posttranscriptional silencing.


Assuntos
Begomovirus , Coinfecção , Solanum lycopersicum , Coinfecção/genética , Begomovirus/genética , Transcriptoma , RNA Interferente Pequeno/genética , Genes Virais , RNA de Cadeia Dupla , DNA , Doenças das Plantas/genética
3.
Nucleic Acids Res ; 52(D1): D304-D310, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37986224

RESUMO

TarBase is a reference database dedicated to produce, curate and deliver high quality experimentally-supported microRNA (miRNA) targets on protein-coding transcripts. In its latest version (v9.0, https://dianalab.e-ce.uth.gr/tarbasev9), it pushes the envelope by introducing virally-encoded miRNAs, interactions leading to target-directed miRNA degradation (TDMD) events and the largest collection of miRNA-gene interactions to date in a plethora of experimental settings, tissues and cell-types. It catalogues ∼6 million entries, comprising ∼2 million unique miRNA-gene pairs, supported by 37 experimental (high- and low-yield) protocols in 172 tissues and cell-types. Interactions are annotated with rich metadata including information on genes/transcripts, miRNAs, samples, experimental contexts and publications, while millions of miRNA-binding locations are also provided at cell-type resolution. A completely re-designed interface with state-of-the-art web technologies, incorporates more features, and allows flexible and ingenious use. The new interface provides the capability to design sophisticated queries with numerous filtering criteria including cell lines, experimental conditions, cell types, experimental methods, species and/or tissues of interest. Additionally, a plethora of fine-tuning capacities have been integrated to the platform, offering the refinement of the returned interactions based on miRNA confidence and expression levels, while boundless local retrieval of the offered interactions and metadata is enabled.


Assuntos
Bases de Dados de Ácidos Nucleicos , MicroRNAs , Genes Virais/genética , Internet , MicroRNAs/genética , MicroRNAs/metabolismo , Animais
4.
J Basic Microbiol ; 64(2): e2300569, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38078780

RESUMO

Viruses exist anywhere on earth where there is life, and among them, virus-encoded auxiliary metabolic genes (AMGs) can maintain ecosystem balance and play a major role in the global ecosystem. Although the function of AMGs has been widely reported, the genetic diversity of AMGs in natural ecosystems is still poorly understood. Exploring the genetic diversity of viral community-wide AMGs is essential to gain insight into the complex interactions between viruses and hosts. In this article, we studied the phylogenetic tree, principal co-ordinates analysis (PCoA), α diversity, and metabolic pathways of viral auxiliary metabolism genes involved in the pentose phosphate pathway (PPP) through metagenomics, and the changes of metabolites and genes of host bacteria were further studied by using Pseudomonas mandelii SW-3 and its lytic phage based on metabolic flow and AMGs expression. We found that the viral AMGs in the Napahai plateau wetland were created by a combination of various external forces, which contributed to the rich genetic diversity, uniqueness, and differences of the virus, which promoted the reproduction of offspring and better adaptation to the environment. Overall, this study systematically describes the genetic diversity of AMGs associated with the PPP in plateau wetland ecosystems and further expands the understanding of phage-host unique interactions.


Assuntos
Bacteriófagos , Vírus , Ecossistema , Áreas Alagadas , Via de Pentose Fosfato/genética , Filogenia , Genes Virais , Bacteriófagos/genética , Genoma Viral
5.
mSystems ; 9(1): e0071323, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38095866

RESUMO

The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic that emerged in 2019 has been an unprecedented event in international science, as it has been possible to sequence millions of genomes, tracking their evolution very closely. This has enabled various types of secondary analyses of these genomes, including the measurement of their sequence selection pressure. In this work, we have been able to measure the selective pressure of all the described SARS-CoV-2 genes, even analyzed by sequence regions, and we show how this type of analysis allows us to separate the genes between those subject to positive selection (usually those that code for surface proteins or those exposed to the host immune system) and those subject to negative selection because they require greater conservation of their structure and function. We have also seen that when another gene with an overlapping reading frame appears within a gene sequence, the overlapping sequence between the two genes evolves under a stronger purifying selection than the average of the non-overlapping regions of the main gene. We propose this type of analysis as a useful tool for locating and analyzing all the genes of a viral genome when an adequate number of sequences are available.IMPORTANCEWe have analyzed the selection pressure of all severe acute respiratory syndrome coronavirus 2 genes by means of the nonsynonymous (Ka) to synonymous (Ks) substitution rate. We found that protein-coding genes are exposed to strong positive selection, especially in the regions of interaction with other molecules (host receptor and genome of the virus itself). However, overlapping coding regions are more protected and show negative selection. This suggests that this measure could be used to study viral gene function as well as overlapping genes.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Proteínas , Genoma Viral/genética , Genes Virais/genética
6.
Mol Biol Rep ; 51(1): 23, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38117315

RESUMO

The potential active chemicals found in medicinal plants, which have long been employed as natural medicines, are abundant. Exploring the genes responsible for producing these compounds has given new insights into medicinal plant research. Previously, the authentication of medicinal plants was done via DNA marker sequencing. With the advancement of sequencing technology, several new techniques like next-generation sequencing, single molecule sequencing, and fourth-generation sequencing have emerged. These techniques enshrined the role of molecular approaches for medicinal plants because all the genes involved in the biosynthesis of medicinal compound(s) could be identified through RNA-seq analysis. In several research insights, transcriptome data have also been used for the identification of biosynthesis pathways. miRNAs in several medicinal plants and their role in the biosynthesis pathway as well as regulation of the disease-causing genes were also identified. In several research articles, an in silico study was also found to be effective in identifying the inhibitory effect of medicinal plant-based compounds against virus' gene(s). The use of advanced analytical methods like spectroscopy and chromatography in metabolite proofing of secondary metabolites has also been reported in several recent research findings. Furthermore, advancement in molecular and analytic methods will give new insight into studying the traditionally important medicinal plants that are still unexplored.


Assuntos
MicroRNAs , Plantas Medicinais , Plantas Medicinais/genética , Sequenciamento de Nucleotídeos em Larga Escala , Análise de Sequência de DNA , Genes Virais , Zidovudina
7.
Viruses ; 15(10)2023 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-37896872

RESUMO

A nucleus-like structure composed of phage-encoded proteins and containing replicating viral DNA is formed in Pseudomonas aeruginosa cells infected by jumbo bacteriophage phiKZ. The PhiKZ genes are transcribed independently from host RNA polymerase (RNAP) by two RNAPs encoded by the phage. The virion RNAP (vRNAP) transcribes early viral genes and must be injected into the cell with phage DNA. The non-virion RNAP (nvRNAP) is composed of early gene products and transcribes late viral genes. In this work, the dynamics of phage RNAPs localization during phage phiKZ infection were studied. We provide direct evidence of PhiKZ vRNAP injection in infected cells and show that it is excluded from the phage nucleus. The nvRNAP is synthesized shortly after the onset of infection and localizes in the nucleus. We propose that spatial separation of two phage RNAPs allows coordinated expression of phage genes belonging to different temporal classes.


Assuntos
Bacteriófagos , Fagos de Pseudomonas , Bacteriófagos/genética , Proteínas Virais/metabolismo , Fagos de Pseudomonas/metabolismo , RNA Polimerases Dirigidas por DNA/metabolismo , Genes Virais
8.
Res Vet Sci ; 164: 105033, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37804663

RESUMO

Pseudorabies virus (PRV) belongs to the species of alphaherpesvirus that can cause substantial economic losses to the world swine industry. Therefore, research on anti-PRV compounds is of great value. In this study, it was found that ginkgolic acid could efficiently inhibit the replication of PRV, and the IC50 and CC50 were 3.407 µM and 102.3 µM, respectively. Moreover, it was discovered that ginkgolic acid had no effect on the adsorption, entry, and release stages of the PRV replication cycle. Importantly, it was found that ginkgolic acid could significantly suppress the transcription of PRV late genes, while the transcription of viral immediate early and early genes was not affected. Finally, in vivo experiments showed that ginkgolic acid could significantly reduce the viral load of PRV in multiple tissues and increase 30% survival rate of mice upon the challenge of PRV. Taken together, a novel PRV replication inhibitor, ginkgolic acid, which worked through suppressing the transcription of the late genes, was found in this study. This study provides a potential therapy method for the infection of PRV.


Assuntos
Herpesvirus Suídeo 1 , Pseudorraiva , Doenças dos Suínos , Camundongos , Animais , Suínos , Herpesvirus Suídeo 1/genética , Genes Virais , Replicação Viral
9.
J Virol ; 97(9): e0088523, 2023 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-37695054

RESUMO

ADP-ribosyltransferases (ARTs) mediate the transfer of ADP-ribose from NAD+ to protein or nucleic acid substrates. This modification can be removed by several different types of proteins, including macrodomains. Several ARTs, also known as PARPs, are stimulated by interferon indicating ADP-ribosylation is an important aspect of the innate immune response. All coronaviruses (CoVs) encode for a highly conserved macrodomain (Mac1) that is critical for CoVs to replicate and cause disease, indicating that ADP-ribosylation can effectively control coronavirus infection. Our siRNA screen indicated that PARP12 might inhibit the replication of a murine hepatitis virus (MHV) Mac1 mutant virus in bone-marrow-derived macrophages (BMDMs). To conclusively demonstrate that PARP12 is a key mediator of the antiviral response to CoVs both in cell culture and in vivo, we produced PARP12-/-mice and tested the ability of MHV A59 (hepatotropic/neurotropic) and JHM (neurotropic) Mac1 mutant viruses to replicate and cause disease in these mice. Notably, in the absence of PARP12, Mac1 mutant replication was increased in BMDMs and mice. In addition, liver pathology was also increased in A59-infected mice. However, the PARP12 knockout did not restore Mac1 mutant virus replication to WT virus levels in all cell or tissue types and did not significantly increase the lethality of Mac1 mutant viruses. These results demonstrate that while PARP12 inhibits MHV Mac1 mutant virus infection, additional PARPs or innate immune factors must contribute to the extreme attenuation of this virus in mice. IMPORTANCE Over the last decade, the importance of ADP-ribosyltransferases (ARTs), also known as PARPs, in the antiviral response has gained increased significance as several were shown to either restrict virus replication or impact innate immune responses. However, there are few studies showing ART-mediated inhibition of virus replication or pathogenesis in animal models. We found that the CoV macrodomain (Mac1) was required to prevent ART-mediated inhibition of virus replication in cell culture. Using knockout mice, we found that PARP12, an interferon-stimulated ART, was required to repress the replication of a Mac1 mutant CoV both in cell culture and in mice, demonstrating that PARP12 represses coronavirus replication. However, the deletion of PARP12 did not fully rescue Mac1 mutant virus replication or pathogenesis, indicating that multiple PARPs function to counter coronavirus infection.


Assuntos
Genes Virais , Vírus da Hepatite Murina , Mutação , Poli(ADP-Ribose) Polimerases , Replicação Viral , Animais , Camundongos , Infecções por Coronavirus/virologia , Modelos Animais de Doenças , Interferons/imunologia , Camundongos Knockout , Vírus da Hepatite Murina/genética , Vírus da Hepatite Murina/crescimento & desenvolvimento , Vírus da Hepatite Murina/metabolismo , Vírus da Hepatite Murina/patogenicidade , Especificidade de Órgãos , Poli(ADP-Ribose) Polimerases/deficiência , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Replicação Viral/genética , Linhagem Celular
10.
Curr Opin Virol ; 62: 101363, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37672875

RESUMO

As a group, influenza-A viruses (IAV) infect a wide range of animal hosts, however, they are constrained to infecting selected host species by species-specific interactions between the host and virus, that are required for efficient replication of the viral RNA genome. When IAV cross the species barrier, they acquire mutations in the viral genome to enable interactions with the new host factors, or to compensate for their loss. The viral polymerase genes polymerase basic 1, polymerase basic 2, and polymerase-acidic are important sites of host adaptation. In this review, we discuss why the viral polymerase is so vital to the process of host adaptation, look at some of the known viral mutations, and host factors involved in adaptation, particularly of avian IAV to mammalian hosts.


Assuntos
Vírus da Influenza A , Animais , Vírus da Influenza A/genética , Genes Virais , Genoma Viral , Especificidade de Hospedeiro , Mutação , Mamíferos
11.
Elife ; 122023 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-37675839

RESUMO

The ultimate success of a viral infection at the cellular level is determined by the number of progeny virions produced. However, most single-cell studies of infection quantify the expression of viral transcripts and proteins, rather than the amount of progeny virions released from infected cells. Here, we overcome this limitation by simultaneously measuring transcription and progeny production from single influenza virus-infected cells by embedding nucleotide barcodes in the viral genome. We find that viral transcription and progeny production are poorly correlated in single cells. The cells that transcribe the most viral mRNA do not produce the most viral progeny and often represent aberrant infections that fail to express the influenza NS gene. However, only some of the discrepancy between transcription and progeny production can be explained by viral gene absence or mutations: there is also a wide range of progeny production among cells infected by complete unmutated virions. Overall, our results show that viral transcription is a relatively poor predictor of an infected cell's contribution to the progeny population.


Assuntos
Influenza Humana , Humanos , Transcrição Viral , Genes Virais , Genoma Viral , Mutação
12.
Int J Mol Sci ; 24(17)2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37685922

RESUMO

HTLV-1 is an oncogenic human retrovirus and the etiologic agent of the highly aggressive ATL malignancy. Two viral genes, Tax and Hbz, are individually linked to oncogenic transformation and play an important role in the pathogenic process. Consequently, regulation of HTLV-1 gene expression is a central feature in the viral lifecycle and directly contributes to its pathogenic potential. Herein, we identified the cellular transcription factor YBX1 as a binding partner for HBZ. We found YBX1 activated transcription and enhanced Tax-mediated transcription from the viral 5' LTR promoter. Interestingly, YBX1 also interacted with Tax. shRNA-mediated loss of YBX1 decreased transcript and protein abundance of both Tax and HBZ in HTLV-1-transformed T-cell lines, as well as Tax association with the 5' LTR. Conversely, YBX1 transcriptional activation of the 5' LTR promoter was increased in the absence of HBZ. YBX1 was found to be associated with both the 5' and 3' LTRs in HTLV-1-transformed and ATL-derived T-cell lines. Together, these data suggest that YBX1 positively influences transcription from both the 5' and 3' promoter elements. YBX1 is able to interact with Tax and help recruit Tax to the 5' LTR. However, through interactions with HBZ, YBX1 transcriptional activation of the 5' LTR is repressed.


Assuntos
Vírus Linfotrópico T Tipo 1 Humano , Proteína 1 de Ligação a Y-Box , Humanos , Genes Virais , Vírus Linfotrópico T Tipo 1 Humano/genética , Regiões Promotoras Genéticas , RNA Interferente Pequeno , Sequências Repetidas Terminais/genética , Proteína 1 de Ligação a Y-Box/genética
13.
Stem Cell Res Ther ; 14(1): 249, 2023 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-37705046

RESUMO

BACKGROUND: Cardiovascular complications significantly augment the overall COVID-19 mortality, largely due to the susceptibility of human cardiomyocytes (CMs) to SARS-CoV-2 virus. SARS-CoV-2 virus encodes 27 genes, whose specific impacts on CM health are not fully understood. This study elucidates the deleterious effects of SARS-CoV-2 genes Nsp6, M, and Nsp8 on human CMs. METHODS: CMs were derived from human pluripotent stem cells (hPSCs), including human embryonic stem cells and induced pluripotent stem cells, using 2D and 3D differentiation methods. We overexpressed Nsp6, M, or Nsp8 in hPSCs and then applied whole mRNA-seq and mass spectrometry for multi-omics analysis. Co-immunoprecipitation mass spectrometry was utilized to map the protein interaction networks of Nsp6, M, and Nsp8 within host hiPSC-CMs. RESULTS: Nsp6, Nsp8, and M globally perturb the transcriptome and proteome of hPSC-CMs. SARS-CoV-2 infection and the overexpression of Nsp6, Nsp8, or M coherently upregulated genes associated with apoptosis and immune/inflammation pathways, whereas downregulated genes linked to heart contraction and functions. Global interactome analysis revealed interactions between Nsp6, Nsp8, and M with ATPase subunits. Overexpression of Nsp6, Nsp8, or M significantly reduced cellular ATP levels, markedly increased apoptosis, and compromised Ca2+ handling in hPSC-CMs. Importantly, administration of FDA-approved drugs, ivermectin and meclizine, could restore ATP levels, thereby mitigating apoptosis and dysfunction in hPSC-CMs overexpressing Nsp6, Nsp8, or M. CONCLUSION: Overall, our findings uncover the extensive damaging effects of Nsp6, Nsp8, and M on hPSC-CMs, underlining the crucial role of ATP homeostasis in CM death and functional abnormalities induced by these SARS-CoV-2 genes, and reveal the potential therapeutic strategies to alleviate these detrimental effects with FDA-approved drugs.


Assuntos
COVID-19 , Células-Tronco Pluripotentes , Humanos , Miócitos Cardíacos , SARS-CoV-2 , Genes Virais , Trifosfato de Adenosina
14.
J Med Virol ; 95(9): e29087, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37707319

RESUMO

Understanding the cellular host factors that promote and inhibit viral entry is important for identifying viral countermeasures. CRISPR whole-genome screens can be used to rapidly discover host factors that contribute to or impair viral entry. However, when using live viruses and cellular lethality for selection, these screens can identify an overwhelming number of genes without specificity for the stage of the viral infection cycle. New screening methods are needed to identify host machinery contributing to specific steps of viral infection. Here, we developed a CRISPR whole-genome screen and counter-screen strategy based on a pseudoviral platform that allowed identification of genes specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike and vesicular stomatitis virus glycoprotein (VSV-G) mediated entry. Screening of SARS-CoV-2 spike and VSV-G on the same lentiviral pseudovirus allowed the identification of entry-specific genes relative to genes associated with retro-transcription, integration, and reporter expression from the lentiviral pseudovirus. Second, a Cre-Gag fusion protein packaged into the pseudovirus was used to bypass retro-transcription and integration by directly activating a floxed fluorescent protein reporter upon entry  reduced the number of gene hits and increase specificity for viral entry. Our approach correctly identified SARS-CoV-2 and VSV-G receptors ACE2 and low-density lipoprotein receptors, respectively, and distinguished genes associated with retroviral reporter expression from envelope-mediated entry. Moreover, the CRE-Gag fusion/flox reporter increased the screen specificity for viral entry-associated genes. Validation of a few hits demonstrates that this approach distinguishes envelope-specific host factors from genes affecting reporter expression. Overall, this approach provides a new strategy for identifying host genes influencing viral entry without the confounding complexity of live-viral screens which produce long gene lists associated with all aspects of viral pathogenesis and replication.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Genes Virais , Receptores Virais
15.
AIDS Res Ther ; 20(1): 66, 2023 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-37691100

RESUMO

Human immunodeficiency virus type 1 (HIV-1) is the primary epidemic strain in China. Its genome contains two regulatory genes (tat and rev), three structural genes (gag, pol, and env), and four accessory genes (nef, vpr, vpu, and vif). Long terminal repeats (LTRs) in thegenome regulate integration, duplication, and expression of viral gene. The permissibility of HIV-1 infection hinges on the host cell cycle status. HIV-1 replicates by exploiting various cellular processes via upregulation or downregulation of specific cellular proteins that also control viral pathogenesis. For example, HIV-1 regulates the life cycle of p53, which in turn contributes significantly to HIV-1 pathogenesis. In this article, we review the interaction between HIV-1-associated factors and p53, providing information on their regulatory and molecular mechanisms, hinting possible directions for further research.


Assuntos
Infecções por HIV , HIV-1 , Humanos , HIV-1/genética , Proteína Supressora de Tumor p53/genética , China , Genes Virais
16.
J Virol ; 97(10): e0096023, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37754762

RESUMO

IMPORTANCE: Infection with herpes simplex virus 1 (HSV-1) leads to lifelong infection due to the virus's remarkable ability to control transcription of its own genome, resulting in two transcriptional programs: lytic (highly active) and latent (restricted). The lytic program requires immediate early (IE) proteins to first repress transcription of late viral genes, which then undergo sequential de-repression, leading to a specific sequence of gene expression. Here, we show that the IE ICP4 functions to regulate the cascade by limiting RNA polymerase initiation at immediate early times. However, late viral genes that initiate too early in the absence of ICP4 do not yield mRNA as transcription stalls within gene bodies. It follows that other regulatory steps intercede to prevent elongation of genes at the incorrect time, demonstrating the precise control HSV-1 exerts over its own transcription.


Assuntos
Regulação Viral da Expressão Gênica , Herpesvirus Humano 1 , Proteínas Imediatamente Precoces , Transcrição Gênica , Humanos , Genes Virais/genética , Herpes Simples/virologia , Herpesvirus Humano 1/genética , Proteínas Imediatamente Precoces/deficiência , Proteínas Imediatamente Precoces/metabolismo , Iniciação da Transcrição Genética , Elongação da Transcrição Genética , Terminação da Transcrição Genética
17.
J Virol ; 97(10): e0070423, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37768081

RESUMO

IMPORTANCE: African swine fever (ASF) caused by ASF virus (ASFV) is a highly contagious and acute hemorrhagic viral disease in domestic pigs. Until now, no effective commercial vaccine and antiviral drugs are available for ASF control. Here, we generated a new live-attenuated vaccine candidate (ASFV-ΔH240R-Δ7R) by deleting H240R and MGF505-7R genes from the highly pathogenic ASFV HLJ/18 genome. Piglets immunized with ASFV-ΔH240R-Δ7R were safe without any ASF-related signs and produced specific antibodies against p30. Challenged with a virulent ASFV HLJ/18, the piglets immunized with high-dose group (105 HAD50) exhibited 100% protection without clinical symptoms, showing that low levels of virus replication with no observed pathogenicity by postmortem and histological analysis. Overall, our results provided a new strategy by designing live-attenuated vaccine candidate, resulting in protection against ASFV infection.


Assuntos
Vírus da Febre Suína Africana , Deleção de Genes , Genes Virais , Vacinas Atenuadas , Vacinas Virais , Animais , Febre Suína Africana/imunologia , Febre Suína Africana/prevenção & controle , Febre Suína Africana/virologia , Vírus da Febre Suína Africana/classificação , Vírus da Febre Suína Africana/imunologia , Vírus da Febre Suína Africana/patogenicidade , Sus scrofa/virologia , Vacinas Atenuadas/imunologia , Proteínas Virais/genética , Vacinas Virais/genética , Vacinas Virais/imunologia , Virulência , Replicação Viral , Genes Virais/genética
18.
Vet Microbiol ; 284: 109835, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37515978

RESUMO

African swine fever virus (ASFV) can accumulate and survive in leeches for a long time. The reasons for the survival of ASFV in leeches are not entirely clear. Here, we elucidate the virus survival pathway in infected leeches. One of the questions reported previously is addressed in this article. How the virus concentration in the body of the leech is equal to or higher than in the water infected with ASFV? Examination of blood swallowed by leeches reveals that the blood cells retain their morphological characteristics for several weeks. It can explain the long-term persistence of the high levels of ASFV in the leeches that ingested ASFV-infected pig blood. qRT-PCR assay showed the transcription of ASFV genes in infected leeches. However, the infectious particles of the virus measured by HADU haven't increased. Quantitative studies of the ASFV revealed a high content of both viral genes and infectious particles in the skin of leeches compared with other body parts. Electron microscopy analysis revealed the ability of the ASFV to effectively bind to the skin surface of the leeches, which explained the high concentrations of ASFV in the leeches' skin. A significant difference in the transcriptional activity between early and late viral genes indicates that the virus entered the initial stage of replication, but for some reason failed to complete it, which is typical of abortive infections.


Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Sanguessugas , Doenças dos Suínos , Suínos , Animais , Vírus da Febre Suína Africana/genética , Sanguessugas/genética , Genes Virais , Replicação Viral , Doenças dos Suínos/genética
19.
G3 (Bethesda) ; 13(10)2023 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-37345948

RESUMO

The parasitoid wasp Venturia canescens is an important biological control agent of stored products moth pests and serves as a model to study the function and evolution of domesticated endogenous viruses (DEVs). The DEVs discovered in V. canescens are known as virus-like particles (VcVLPs), which are produced using nudivirus-derived components and incorporate wasp-derived virulence proteins instead of packaged nucleic acids. Previous studies of virus-derived components in the V. canescens genome identified 53 nudivirus-like genes organized in six gene clusters and several viral pseudogenes, but how VcVLP genes are organized among wasp chromosomes following their integration in the ancestral wasp genome is largely unknown. Here, we present a chromosomal scale genome of V. canescens consisting of 11 chromosomes and 56 unplaced small scaffolds. The genome size is 290.8 Mbp with a N50 scaffold size of 24.99 Mbp. A high-quality gene set including 11,831 protein-coding genes were produced using RNA-Seq data as well as publicly available peptide sequences from related Hymenoptera. A manual annotation of genes of viral origin produced 61 intact and 19 pseudogenized nudivirus-derived genes. The genome assembly revealed that two previously identified clusters were joined into a single cluster and a total of 5 gene clusters comprising of 60 intact nudivirus-derived genes were located in three chromosomes. In contrast, pseudogenes are dispersed among 8 chromosomes with only 4 pseudogenes associated with nudivirus gene clusters. The architecture of genes encoding VcVLP components suggests it originates from a recent virus acquisition and there is a link between the processes of dispersal and pseudogenization. This high-quality genome assembly and annotation represents the first chromosome-scale assembly for parasitoid wasps associated with VLPs, and is publicly available in the National Center for Biotechnology Information Genome and RefSeq databases, providing a valuable resource for future studies of DEVs in parasitoid wasps.


Assuntos
Mariposas , Vespas , Animais , Vespas/genética , Domesticação , Genes Virais , Mariposas/genética , Cromossomos
20.
Nat Commun ; 14(1): 3609, 2023 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-37330604

RESUMO

Tailed bacteriophages (order, Caudovirales) account for the majority of all phages. However, the long flexible tail of siphophages hinders comprehensive investigation of the mechanism of viral gene delivery. Here, we report the atomic capsid and in-situ structures of the tail machine of the marine siphophage, vB_DshS-R4C (R4C), which infects Roseobacter. The R4C virion, comprising 12 distinct structural protein components, has a unique five-fold vertex of the icosahedral capsid that allows genome delivery. The specific position and interaction pattern of the tail tube proteins determine the atypical long rigid tail of R4C, and further provide negative charge distribution within the tail tube. A ratchet mechanism assists in DNA transmission, which is initiated by an absorption device that structurally resembles the phage-like particle, RcGTA. Overall, these results provide in-depth knowledge into the intact structure and underlining DNA delivery mechanism for the ecologically important siphophages.


Assuntos
Bacteriófagos , Caudovirales , Genoma Viral , Bacteriófagos/genética , Bacteriófagos/química , Genes Virais , Caudovirales/genética , Proteínas do Capsídeo/genética , DNA , DNA Viral/genética
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