Virology Journal最新文献

Therapeutic human papillomavirus (HPV) DNA vaccine is an attractive option to control existed HPV infection and related lesions. The two early viral oncoproteins, E6 and E7, are continuously expressed in most HPV-related pre- and cancerous cells, and are ideal targets for therapeutic vaccines. We have previously developed an HPV 16 DNA vaccine encoding a modified E7/HSP70 (mE7/HSP70) fusion protein, which demonstrated significant antitumor effects in murine models. In this study, we employed multifaceted approach to enhance the potency of the HPV16 DNA vaccine. Strategies including inserting CpG oligodeoxynucleotide (CpG ODNs) into the vaccine vector backbone, selecting cytokine gene adjuvants, combining plasmids encoding mE6/HSP70 and mE7/HSP70, and utilizing electroporation for vaccination. Our findings revealed that mice immunized with CpG-modified vaccines, coupled with an IL-28B gene adjuvant exhibited heightened antigen-specific CD8⁺ T cell responses. Additionally, the combination of mE6/HSP70 and mE7/HSP70 plasmids synergistically enhanced the specific CD8⁺ T cell response. Furthermore, vaccination with CpG-modified mE7/HSP70 and mE6/HSP70 plasmids, alongside the Interleukin-28B (IL-28B) gene adjuvant, generated substantial preventive and therapeutic antitumor effects against HPV E6- and E7-expressing tumors in C57BL/6 mice. These results suggested that integrating these multiple strategies into an HPV DNA vaccine holds promise for effectively controlling HPV infection and related diseases.

Acute kidney injury (AKI) is a condition that can result in changes in both urine production and creatinine levels in the bloodstream, complicating the treatment process and worsening outcomes for many hospitalized patients. BK polyomavirus (BKPyV), a member of the Polyomaviridae family, is prevalent in the population and remains latent in the body. It can reactivate in individuals with a compromised immune system, particularly post-kidney transplant, and can activate various transcription factors and immune mediators. Although reactivation is often asymptomatic, it can present as AKI, which is a risk factor for early loss of the transplanted organ. The immune response to BKPyV is crucial in controlling the virus and safeguarding organs from damage during infection. Understanding BKPyV pathways may offer novel opportunities for effectively treating BKPyV-associated complications. This review seeks to elucidate the potential mechanisms by which BKPyV reactivation can lead to AKI by analyzing various signaling pathways, as well as the identification of molecular mechanisms that BKPyV may utilize to induce AKI.

Background: Despite numerous genetic studies on Infectious Bronchitis Virus (IBV), many strains from the Middle East remain misclassified or unclassified. Genotype 1 (GI-1) is found globally, while genotype 23 (GI-23) has emerged as the predominant genotype in the Middle East region, evolving continuously through inter- and intra-genotypic recombination. The GI-23 genotype is now enzootic in Europe and Asia.

Methods: Over a 24-month period from May 2022 to June 2024, 360 samples were collected from 19 layer and 3 broiler poultry farms in central Saudi Arabia. The chickens exhibited reduced laying rates and symptoms such as weakness and respiratory distress, while broilers showed respiratory issues. Samples, including tracheal swabs and various tissue specimens, were pooled, homogenized, and stored at -20 °C prior to PCR analysis. The samples underwent virus isolation in embryonated chicken eggs, RNA extraction using automated systems, and detection of IBV through real-time RT-PCR targeting a conserved 5'-UTR fragment. Full-length genome sequencing was performed, and recombination analysis was conducted using RDP 4.6.

Results: Saudi IBV strains were found to cluster into genotypes GI-1 and GI-23.1. The study identified critical amino acid substitutions in the hypervariable regions of the spike protein and detected recombination events in the ORF1ab, N, M, 3ab, and 5ab genes, with nsp3 of the ORF1ab showing the greatest number of recombination events.

Conclusion: The multiple inter- and intra-genotypic recombination events that were detected in different genes indicate that the circulating IBV strains do not share a single ancestor but have emerged through successive recombination events.

Objectives: To analyze the molecular epidemiological characteristics of influenza viruses in influenza-like cases in Chongqing Hi-Tech Zone, China, to provide data support and a scientific basis for optimizing influenza prevention and control strategies in the region.

Materials and methods: A retrospective analysis was conducted on the molecular epidemiological characteristics of influenza viruses in influenza-like cases at a hospital in Chongqing Hi-Tech Zone from 2021 to 2024. Colloidal gold detection of viral antibodies, fluorescent PCR detection of nucleic acids, and gene sequencing were used to identify the different subtypes.

Results: Among 39,986 ILI specimens tested using the immunocolloid gold method, 6,616 influenza viruses were detected, with a detection rate of 16.54%. Infections included 4,464 influenza A viruses (67.50%), 2,033 influenza B viruses (30.73%), and 119 co-infections of influenza A and B viruses (1.77%).In this region, H3N2 was the predominant subtype of influenza A, and Victoria was the main subtype of influenza B.

Conclusion: Influenza epidemics in the winter and spring seasons in Chongqing Hi-Tech Zone were predominantly caused by influenza A, with influenza B also circulating. Influenza A strains were mainly H3N2, while influenza B strains were primarily Victoria.

Background: The hand, foot and mouth disease (HFMD) was caused by species of Enterovirus A and Enterovirus B in the Asian-Pacific region. Broad-spectrum monoclonal antibodies (mAb) that can bind multiple serotypes of enteroviruses have gradually become a research hotspot in the diagnosis, prevention and treatment of HFMD.

Methods: In this study, a mAb 1H4 was obtained using monoclonal antibody technology by immunizing purified virus particles of Coxsackievirus A5 (CV-A5). Examined by indirect immunofluorescence and Western blotting, 1H4 detected successfully all seven selected serotypes CV-A2, CV-A4, CV-A5, CV-A6, CV-A10, CV-A16 and EV-A71 of Enterovirus A and targeted structural protein VP1.

Results: The mAb 1H4 showed no cross-reactivity to strains of Enterovirus B and Enterovirus C. A linear epitope ₂₀₂WFYDGYPT₂₀₉ was identified as the minimal binding region of 1H4 by indirect ELISAs with overlapped and truncated peptides of VP1. Alanine scanning test found that W₂₀₂, F₂₀₃, D₂₀₅, G₂₀₆, Y₂₀₇, P₂₀₈, and T₂₀₉ were key residues in the epitope region. BLAST of the epitope in the NCBI genus Enterovirus protein database indicates that the epitope sequence is highly conserved among Enterovirus A species, but not among the other Enterovirus species.

Conclusions: The results suggest that the mAb 1H4 may be a useful tool for development with a cost-effective and accurate method for surveillance and early differentiation of serotypes from Enterovirus A species to other species.

Human papillomavirus (HPV) is the most prevalent sexually transmitted infection globally, with significant implications for various anogenital cancers, such as vulval, vaginal, anal, penile, head and neck cancers. HPV infections have been linked to the induction of inflammation. In contrast, Interleukin-37 (IL-37) is recognized as an anti-inflammatory cytokine. In this study, two distinct types of oral epithelial cells were employed to investigate the impact of HPV on inflammation. The experimental outcomes unequivocally demonstrated that human papillomavirus (HPV) elicited a pronounced and statistically significant induction of inflammatory responses within both varieties of oral epithelial cells under investigation. Interestingly, IL-37 exhibited a mitigating effect, attenuating the HPV-induced inflammation in oral epithelial cells. Further exploration into the molecular mechanisms involved revealed that knockdown (KD) of PI3K compromised the anti-inflammatory effects of IL-37 in response to HPV. Similarly, KD of AKT was found to compromise the regulatory effects of IL-37 on HPV-induced inflammation. Notably, KD of mTOR was identified as a key factor, compromising the anti-inflammatory effects of IL-37 in the context of HPV-induced inflammation. Additionally, the study uncovered that the mTOR inhibitor, rapamycin, could effectively compromise the effects of IL-37 on HPV-induced inflammation. These findings contribute valuable insights into the intricate pathogenesis of HPV-induced inflammation and may pave the way for the development of innovative treatments for this condition.

PEDV is a highly contagious enteric pathogen that can cause severe diarrhea and death in neonatal pigs. Despite extensive research, the molecular mechanisms of host's response to PEDV infection remain unclear. In this study, differentially expressed genes (DEGs), time-specific coexpression modules, and key regulatory genes associated with PEDV infection were identified. The analysis revealed 2,275, 1,492, and 3,409 DEGs in infected vs. mock-treated pigs at 12 h, 24 h, and 48 h, respectively. Time series analysis revealed that the upregulated genes were involved mainly in antiviral pathways such as the viral defense response and the regulation of immune system processes. Protein-protein interaction network analysis identified the top 20 core genes in the interaction network, which included six upregulated genes (TFRC, SUOX, RMI1, CD74, IFIH1, and CD86) and 14 downregulated genes (FOS, CDC6, CDCA3, PIK3R2, TUFM, VARS, ASF1B, POLD1, MCM8, POLA1, CDC45, BCS1L, RAD51, and RPA2). In addition, GSEA enrichment analysis revealed that pathways such as DNA replication and homologous recombination involving RAD51, CDC6, and RPA2 were significantly inhibited during viral infection. Our findings not only reveal dynamic changes in the transcriptome profile of PEDV-infected IPEC-J2 cells but also provide novel insights into the mechanism of PEDV infection of the host.

The three members of the genus capripoxvirus (CaPV), lumpy skin disease virus (LSDV), sheeppox virus (SPPV), and goatpox virus (GTPV) have common hosts and areas of overlapping geographical distribution with Rift Valley fever virus (RVFV). Hence, to ensure more cost-effective disease surveillance we developed and evaluated a Luminex assay for the simultaneous detection of antibodies against CaPV and RVFV in domestic ruminants. In cattle, the assay had a sensitivity (Se) of 98.7% and a specificity (Sp) of 98.3% in detecting anti-LSDV antibodies; both diagnostic parameters were 100% for the detection of anti-RVFV antibodies in this species. In sheep and goats, Se and Sp were 100% for the detection of anti-SPPV and anti-GTPV antibodies while they were 100% and 98.9%, respectively for the detection of anti-RVFV antibody. The assay did not cross react with anti-parapoxvirus antibodies of cattle, sheep, and goats. This multiplex serological assay offers a practical tool for accurate detection and monitoring of the immunological status of domestic ruminant populations against veterinary and socio-economically important capripox- and phleboviral infections, thus has the potential to aid in the strategic application of vaccination programmes.

Background: Canine adipose-derived mesenchymal stem cells (cAD-MSCs) demonstrate promising tissue repair and regeneration capabilities. However, the procurement and preservation of these cells or their secreted factors for therapeutic applications pose a risk of viral contamination, and the consequences for cAD-MSCs remain unexplored. Consequently, this research sought to assess the impact of canid alphaherpesvirus 1 (CHV) on the functional attributes of cAD-MSCs, including gene expression profiles and secretome composition.

Methods: To this end, abdominal adipose tissue from 12 healthy dogs was harvested to isolate cAD-MSCs. These samples were tested for CHV contamination before introducing a wild-type CHV strain via serial passages. Following CHV infection, real-time reverse transcription-polymerase chain reaction array and liquid chromatography with tandem mass spectrometry assessments enabled analyses of gene expression and secretome's proteomic profile, respectively.

Results: This study showed that the initial cAD-MSC populations were devoid of CHV. cAD-MSCs showed susceptibility to infection with wild-type CHV, leading to notable modifications in gene expression and secretome profile. The observed genomic variations in gene expression indicate potential impacts on the stemness, migration, and other functional properties of cAD-MSCs, highlighting the need for further studies to evaluate their functional capacity post-infection. Moreover, gene expression and secretome analyses suggest a shift in stem cell differentiation toward an adipogenic phenotype.

Conclusion: To the best of our knowledge, this is the first study of the effects of virus infection on gene expression and secretome composition in cAD-MSCs. The outcomes of our study underscore the imperative of routine viral screening prior to the therapeutic use of cAD-MSCs. Moreover, these findings provide novel insights into the pathogenic mechanisms of CHV and pave the way for future canine stem cell and virus research.