Virus Genes最新文献

One of the significant issues in treating bacterial infections is the increasing prevalence of extensively drug-resistant (XDR) strains of Acinetobacter baumannii. In the face of limited or no viable treatment options for extensively drug-resistant (XDR) bacteria, there is a renewed interest in utilizing bacteriophages as a treatment option. Three Acinetobacter phages (vB_AbaS_Ftm, vB_AbaS_Eva, and vB_AbaS_Gln) were identified from hospital sewage and analyzed for their morphology, host ranges, and their genome sequences were determined and annotated. These phages and vB_AbaS_SA1 were combined to form a phage cocktail. The antibacterial effects of this cocktail and its combinations with selected antimicrobial agents were evaluated against the XDR A. baumannii strains. The phages exhibited siphovirus morphology. Out of a total of 30 XDR A. baumannii isolates, 33% were sensitive to vB_AbaS_Ftm, 30% to vB_AbaS_Gln, and 16.66% to vB_AbaS_Eva. When these phages were combined with antibiotics, they demonstrated a synergistic effect. The genome sizes of vB_AbaS_Ftm, vB_AbaS_Eva, and vB_AbaS_Gln were 48487, 50174, and 50043 base pairs (bp), respectively, and showed high similarity. Phage cocktail, when combined with antibiotics, showed synergistic effects on extensively drug-resistant (XDR) strains of A. baumannii. However, the need for further study to fully understand the mechanisms of action and potential limitations of using these phages is highlighted.

Atopic dermatitis (AD) is accompanied by changes in skin microbiota, in which abnormal colonization of Staphylococcus aureus is particularly common. The antibiotic treatment is prone to destroy the commensal bacterial community, further exacerbating the microbiome dysbiosis. Elimination of S. aureus through phage-targeted therapies presents a promising method in the treatment strategy of AD. In this study, we isolated a novel phage SAP71, which specifically lysed S. aureus. Genome sequencing showed that SAP71 contained no virulence, lysogenic, or antimicrobial resistance genes, making this lytic phage a potential agent for phage therapy. Moreover, we demonstrated that phage SAP71 was able to significantly improve the skin lesions, reduce the bacterial loads in the skin, and prevent the development of AD-like skin pathological changes in an AD model. In short, phage SAP71 was demonstrated to effectively treat S. aureus infection in AD, which provided a theoretical basis for the clinical phage therapy of AD.

Hepatitis B virus (HBV) infection remains a significant global health challenge, with chronic HBV leading to severe liver diseases, including cirrhosis and hepatocellular carcinoma. Current treatments often fail to eradicate the virus, highlighting the need for innovative therapeutic strategies. The CRISPR/Cas9 system has emerged as a dynamic tool for precise genome editing and presents a promising approach to targeting and eliminating HBV infection. This review provides a comprehensive overview of the advances, challenges, and delivery strategies associated with CRISPR/Cas9-based therapies for HBV. We begin by elucidating the mechanism of the CRISPR/Cas9 system and then explore HBV pathogenesis, focusing on the role of covalently closed circular DNA (cccDNA) and integrated HBV DNA in maintaining chronic infection. CRISPR/Cas9 can disrupt these key viral reservoirs, which are critical for persistent HBV replication and associated liver damage. The application of CRISPR/Cas9 in HBV treatment faces significant challenges, such as off-target effects, delivery efficiency, and immune responses. These challenges are addressed by examining current approaches to enhance the specificity, safety, and efficacy of CRISPR/Cas9. A future perspective on the development and clinical translation of CRISPR/Cas9 therapies for HBV is provided, emphasizing the requirement for further research to improve delivery methods and ensure durable safety and effectiveness. This review underscores the transformative potential of CRISPR/Cas9 in combating HBV and sets the stage for future breakthroughs in the field.

Dengue fever virus (DENV) poses a significant public health risk in tropical and subtropical regions across the world. Although the dengue fever virus (DENV) exhibits significant genetic diversity and has the potential to evolve, there is a lack of comprehensive research on the comparative genomics and evolutionary dynamics of the virus in Pakistan. Phylogenetic analysis demonstrated the circulation of all four dengue virus serotypes (DENV-1, - 2, - 3, and - 4) with prevalent genotypes III and V within DENV-1, cosmopolitan genotype within DENV-2, genotype III within DENV-3, and genotype I within DENV-4 during 2006-2014. Based on the complete envelope region, genome-wide residue signature and genetic diversity indicate that there is a high level of genetic diversity among DENV-1 strains, while DENV-3 strains exhibit the least genetic diversity. Comparative analysis of all four DENV serotypes revealed that certain codons in DENV-2 and -4 were subject to strong purifying selection, while a few codon sites in the envelope region showed evidence of positive selection. These findings provided valuable insights into the comparative genomics and evolutionary pattern of DENV strains reported from Pakistan. Whether those characteristics conferred a fitness advantage to DENV-1 genotypes within a specific geography and time interval warrants further investigations. The findings of the current study will contribute to tracking disease dynamics, understanding virus transmission and evolution, and formulating effective disease control strategies.

Messenger ribonucleic acid (mRNA) was discovered in 1961 as an intermediary for transferring genetic information from DNA to ribosomes for protein synthesis. The COVID-19 pandemic brought worldwide attention to mRNA vaccines. The emergency use authorization of two COVID-19 mRNA vaccines, BNT162b2 and mRNA-1273, were major achievements in the history of vaccine development. Lipid nanoparticles (LNPs), one of the most superior non-viral delivery vectors available, have made many exciting advances in clinical translation as part of the COVID-19 vaccine and therefore has the potential to accelerate the clinical translation of many gene drugs. In addition, due to these small size, biocompatibility and excellent biodegradability, LNPs can efficiently deliver nucleic acids into cells, which is particularly important for current mRNA therapeutic regimens. LNPs are composed cationic or pH-dependent ionizable lipid bilayer, polyethylene glycol (PEG), phospholipids, and cholesterol, represents an advanced system for the delivery of mRNA vaccines. Furthermore, optimization of these four components constituting the LNPs have demonstrated enhanced vaccine efficacy and diminished adverse effects. The incorporation of biodegradable lipids enhance the biocompatibility of LNPs, thereby improving its potential as an efficacious therapeutic approach for a wide range of challenging and intricate diseases, encompassing infectious diseases, liver disorders, cancer, cardiovascular diseases, cerebrovascular conditions, among others. Consequently, this review aims to furnish the scientific community with the most up-to-date information regarding mRNA vaccines and LNP delivery systems.

Black gram (Vigna mungo L.) plants showing yellow mosaic symptoms during 2019-2022 crop seasons were collected randomly from a Dayalbagh field, Agra Region of Uttar Pradesh, India. Total genomic DNA was isolated from the infected leaf samples by the Cetyltrimethylammonium bromide (CTAB) method and subjected to PCR. After viral confirmation, the viral genome was amplified by rolling circle amplification following the standard protocol. The DNA A and DNA B subgenomes were cloned individually as a PstI and BamHI fragment in the pUC18 vector. Positive clones were subjected to DNA sequencing. The results revealed that DNA A and DNA B show the closest nucleotide identity with "mungbean yellow mosaic India virus-[Mungbean], DNA-A, the complete sequence" (GeneBank Accession No AF416742.1) with 98.14% identity, and "mungbean yellow mosaic India virus isolate Mu1-Dholi segment DNA-B, the complete sequence" (GeneBank Accession No MW814723.1) with 97.94% identity, respectively. The new isolate of mungbean yellow mosaic India virus (MYMIV) shows sequence similarity with the coat protein gene of various strains of MYMIV. In the new isolate of MYMIV, a point mutation was observed at the 2036th nucleotide of DNA B, which disrupts the reading frame to introduce a stop codon and thus leading to a decrease in the size of the movement protein gene. In the present study we are reporting the whole genome sequence of the MYMIV Dayalbagh isolate for the first time.

Virome analysis was performed on 174 grape genetic resources from the National Agriculture and Food Research Organization, Japan. A total of 20 bulk samples was prepared by grouping the vines into batches of 6-10 plants. Each of the bulk samples was analyzed using high-throughput sequencing, which detected 27 viruses and 5 viroids, including six viruses and one viroid reported in Japan for the first time (grapevine viruses F, L, and T, grapevine Kizil Sapak virus, grapevine Syrah virus 1, grapevine satellite virus, and grapevine yellow speckle viroid 2). In addition, a novel vitivirus was detected with a maximum nucleotide sequence identity of only 58% to its closest relative, grapevine virus A (GVA). The genome of this novel virus was 7,461 nucleotides in length and encoded five open reading frames showing the typical genomic structure of vitiviruses. Phylogenetic trees of vitiviruses placed it in a distinct position nearest to GVA or grapevine virus F (GVF) in genomes and amino acids of deduced replication-associated protein (RAP) and coat protein (CP). The amino acid sequence identities of RAP and CP with GVA, GVF, and other vitiviruses were a maximum of 53% and 73%, respectively, which were significantly below the species demarcation threshold of 80% in the genus. The low identity and phylogenetic analyses indicate the discovery of a novel vitivirus species provisionally named grapevine virus P.

The complete genome sequence of Orthotospovirus tomatozonae (tomato zonate spot virus, TZSV) isolated in Japan was determined and compared with that of Chinese isolates. The lengths of the S, M, and L segments of the RNA genomes of the Japanese isolate (TZSV-TZ1-3) were 3194, 4675, and 8916 nucleotides, respectively, which were similar to the Chinese isolates. Moreover, the eight motifs on the RNA-dependent RNA polymerase (RdRp) gene were conserved in both TZSV-TZ1-3 and Chinese TZSV isolates (TZSV-Bidens and TZSV-Tomato-YN). The nucleotide identity of the genes among the TZSV isolates was more than 94%, indicating low diversity among viruses. The phylogenetic analysis and the prediction of the cleavage sites in the glycoprotein showed that the TZSV-TZ1-3 isolate was closely related to TZSV-Tomato-YN isolated from China. However, there were unique frameshifts and deletions on the RdRp and glycoprotein genes of the TZSV-Tomato-YN isolate, suggesting that both isolates were genetically distinct. The findings of this study indicate that the TZSV-TZ1-3 isolate originated in China and show the sequence diversity among TZSV isolates.

Orf or contagious ecthyma is a highly contagious, zoonotic, and economically important global viral disease of small ruminants and is endemic in India. Vaccination of susceptible goats/sheep along with suitable recombinant protein-based serological assay will be useful in the control of the infection. In this study, the full-length and truncated versions of F1L encoding gene (ORF 059) of orf virus were cloned into pFasBac HT A vector, transformed in DH10Bac cells, and expressed in insect cells. The full-length and truncated recombinant F1L proteins were expressed as a 6 × histidine-tagged fusion protein for ease of purification by Ni-NTA affinity chromatography under denaturing conditions. A protein with ~ 40 kDa and ~ 35 kDa for full-length and truncated F1L protein, respectively, were expressed and confirmed by SDS-PAGE and western blot. The protein reactivity evaluated by western blot analysis and indirect ELISA using ORFV hyperimmune serum was also found to be reactive. The results of the present study showed that the purified recombinant F1L protein can be used as a diagnostic antigen in sero-surveillance of ORFV infection in small ruminants. To the best of authors' knowledge, this is the first report on the expression of ORFV F1L in insect cells using a baculovirus vector and its successful purification to use as the potential diagnostic antigen in ELISA.

Epstein-Barr virus (EBV) is the first human oncogenic virus known to express microRNAs (miRNAs), which are closely associated with the development of various tumors, including nasopharyngeal and gastric cancers. Stearoyl-CoA Desaturase 1 (SCD1) is a key enzyme in fatty acid synthesis, highly expressed in numerous tumors, promoting tumor growth and metastasis, making it a potential therapeutic target. In this study, we found that SCD1 expression in EBV-associated gastric cancer (EBVaGC) was significantly lower than in EBV-negative gastric cancer (EBVnGC) at both cellular and tissue levels. In addition, EBV-miR-BART20-5p targets the 3′-UTR of SCD1, downregulating its expression. Moreover, overexpression of SCD1 in EBVaGC cells promoted cell migration and proliferation while inhibiting autophagy. These results suggest that EBV-encoded miRNA-BART20-5p may contribute to EBVaGC progression by targeting SCD1.