Interaction Of Virus Research Articles

Modeling the dynamical behavior of the interaction of T-cells and human immunodeficiency virus with saturated incidence

In the last forty years, the rise of HIV has undoubtedly become a major concern in the field of public health, imposing significant economic burdens on affected regions. Consequently, it becomes imperative to undertake comprehensive investigations into the mechanisms governing the dissemination of HIV within the human body. In this work, we have devised a mathematical model that elucidates the intricate interplay between CD4+ T-cells and viruses of HIV, employing the principles of fractional calculus. The production rate of CD4+ T-cells, like other immune cells depends on certain factors such as age, health status, and the presence of infections or diseases. Therefore, we incorporate a variable source term in the dynamics of HIV infection with a saturated incidence rate to enhance the precision of our findings. We introduce the fundamental concepts of fractional operators as a means of scrutinizing the proposed HIV model. To facilitate a deeper understanding of our system, we present an iterative scheme that elucidates the trajectories of the solution pathways of the system. We show the time series analysis of our model through numerical findings to conceptualize and understand the key factors of the system. In addition to this, we present the phase portrait and the oscillatory behavior of the system with the variation of different input parameters. This information can be utilized to predict the long-term behavior of the system, including whether it will converge to a steady state or exhibit periodic or chaotic oscillations.

Epigenetic Mechanisms in Latent Epstein-Barr Virus Infection and Associated Cancers.

The Epstein-Barr Virus (EBV) is a double-stranded DNA-based human tumor virus that was first isolated in 1964 from lymphoma biopsies. Since its initial discovery, EBV has been identified as a major contributor to numerous cancers and chronic autoimmune disorders. The virus is particularly efficient at infecting B-cells but can also infect epithelial cells, utilizing an array of epigenetic strategies to establish long-term latent infection. The association with histone modifications, alteration of DNA methylation patterns in host and viral genomes, and microRNA targeting of host cell factors are core epigenetic strategies that drive interactions between host and virus, which are necessary for viral persistence and progression of EBV-associated diseases. Therefore, understanding epigenetic regulation and its role in post-entry viral dynamics is an elusive area of EBV research. Here, we present current outlooks of EBV epigenetic regulation as it pertains to viral interactions with its host during latent infection and its propensity to induce tumorigenesis. We review the important epigenetic regulators of EBV latency and explore how the strategies involved during latent infection drive differential epigenetic profiles and host-virus interactions in EBV-associated cancers.

Polyphenols and their nanoformulations as potential antibiofilm agents against multidrug-resistant pathogens.

The emergence of multidrug-resistant (MDR) pathogens is a major problem in the therapeutic management of infectious diseases. Among the bacterial resistance mechanisms is the development of an enveloped protein and polysaccharide-hydrated matrix called a biofilm. Polyphenolics have demonstrated beneficial antibacterial effects. Phenolic compounds mediate their antibiofilm effects via disruption of the bacterial membrane, deprivation of substrate, protein binding, binding to adhesion complex, viral fusion blockage and interactions with eukaryotic DNA. However, these compounds have limitations of chemical instability, low bioavailability, poor water solubility and short half-lives. Nanoformulations offer a promising solution to overcome these challenges by enhancing their antibacterial potential. This review summarizes the antibiofilm role of polyphenolics, their underlying mechanisms and their potential role as resistance-modifying agents.

Viral spike-receptor interactions monitored by cryo-electron tomograpy on membranes

Viral spike-receptor interactions monitored by cryo-electron tomograpy on membranes

The Mathematical Modeling of the Host-Virus Interaction in Dengue Virus Infection: A Quantitative Study.

Infectious diseases, such as Dengue fever, pose a significant public health threat. Developing a reliable mathematical model plays a crucial role in quantitatively elucidating the kinetic characteristics of antibody-virus interactions. By integrating previous models and incorporating the antibody dynamic theory, we have constructed a novel and robust model that can accurately simulate the dynamics of antibodies and viruses based on a comprehensive understanding of immunology principles. It explicitly formulates the viral clearance effect of antibodies, along with the positive feedback stimulation of virus-antibody complexes on antibody regeneration. In addition to providing quantitative insights into the dynamics of antibodies and viruses, the model exhibits a high degree of accuracy in capturing the kinetics of viruses and antibodies in Dengue fever patients. This model offers a valuable solution to modeling the differences between primary and secondary Dengue infections concerning IgM/IgG antibodies. Furthermore, it demonstrates that a faster removal rate of antibody-virus complexes might lead to a higher peak viral loading and worse clinical symptom. Moreover, it provides a reasonable explanation for the antibody-dependent enhancement of heterogeneous Dengue infections. Ultimately, this model serves as a foundation for constructing an optimal mathematical model to combat various infectious diseases in the future.

The Dynamic Landscape of Capsid Proteins and Viral RNA Interactions in Flavivirus Genome Packaging and Virus Assembly.

The Flavivirus genus of the Flaviviridae family of enveloped single-stranded RNA viruses encompasses more than 70 members, many of which cause significant disease in humans and livestock. Packaging and assembly of the flavivirus RNA genome is essential for the formation of virions, which requires intricate coordination of genomic RNA, viral structural, and nonstructural proteins in association with virus-induced, modified endoplasmic reticulum (ER) membrane structures. The capsid (C) protein, a small but versatile RNA-binding protein, and the positive single-stranded RNA genome are at the heart of the elusive flavivirus assembly process. The nucleocapsid core, consisting of the genomic RNA encapsidated by C proteins, buds through the ER membrane, which contains viral glycoproteins prM and E organized as trimeric spikes into the lumen, forming an immature virus. During the maturation process, which involves the low pH-mediated structural rearrangement of prM and E and furin cleavage of prM in the secretory pathway, the spiky immature virus with a partially ordered nucleocapsid core becomes a smooth, mature virus with no discernible nucleocapsid. This review focuses on the mechanisms of genome packaging and assembly by examining the structural and functional aspects of C protein and viral RNA. We review the current lexicon of critical C protein features and evaluate interactions between C and genomic RNA in the context of assembly and throughout the life cycle.

Activation of cGAS-STING suppresses coxsackievirus replication via interferon-dependent signaling

Coxsackievirus B3 (CVB3) is a non-enveloped, single-stranded, positive RNA virus known for its role in provoking inflammatory diseases that affect the heart, pancreas, and brain, leading to conditions such as myocarditis, pancreatitis, and meningitis. Currently, there are no FDA-approved drugs treating CVB3 infection; therefore, identifying potential molecular targets for antiviral drug development is imperative. In this study, we examined the possibility of activating the cyclic GMP–AMP (cGAMP) synthase (cGAS)–stimulator of interferon genes (STING) pathway, a cytosolic DNA-sensing pathway that triggers a type-I interferon (IFN) response, in inhibiting CVB3 infection. We found that activation of the cGAS-STING pathway through the application of cGAS (poly dA:dT and herring testes DNA) or STING agonists (2′3′-cGAMP and diamidobenzimidazole), or the overexpression of STING, significantly suppresses CVB3 replication. Conversely, gene-silencing of STING enhances viral replication. Mechanistically, we demonstrated that cGAS-STING activation combats CVB3 infection by inducing IFN response. Notably, we discovered that knockdown of IFN-α/β receptor, a key membrane receptor in type-I IFN signaling, or inhibition of the downstream JAK1/2 signaling with ruxolitinib, mitigates the effects of STING activation, resulting in increased viral protein production. Furthermore, we investigated the interplay between CVB3 and the cGAS-STING pathway. We showed that CVB3 does not trigger cGAS-STING activation; instead, it antagonizes STING and the downstream TBK1 activation induced by cGAMP. In summary, our results provide insights into the interaction of an RNA virus and the DNA-sensing pathway, highlighting the potential for agonist activation of the cGAS-STING pathway in the development of anti-CVB3 drugs.

A Retrospective Analysis of Incidence and Risk Factors for the Development of Secondary Infections Following COVID-19

Abstract Introduction The SARS-CoV-2 virus primarily affects the lungs causing a heightened immune response due to viral and host cell interaction, which prompts the release of proinflammatory cytokines and reduces the defense mechanisms of the immune system, making the patient vulnerable to secondary infections. The study aims to identify the incidence and risk factors for secondary infections developing after COVID-19. Methods and Materials A retrospective study was conducted on 669 patients who were readmitted after COVID-19 to a tertiary care hospital. The development of secondary infections in these populations was identified. The data were collected from the medical records department. Statistical Analysis Incidence was calculated by the ratio of the total number of patients who developed secondary infections among readmitted patients divided by the total number of readmitted patients during the study period. Univariate analysis was performed to identify the statistically significant variables that were used in logistic regression for identifying the risk factors for secondary infection. Statistical analysis was performed in SPSS version 28.0. Results and Discussion In this study, 85 patients were found to have developed secondary infections with an incidence of 12.7%. Among the reported six infections, mucormycosis showed the highest incidence (34.1%), followed by sepsis and urinary tract infection. Nine patients developed tuberculosis as a post-COVID-19 secondary infection. General risk factors for secondary infections include male gender, presence of comorbidities such as diabetes mellitus and chronic kidney disease (CKD), intensive care unit (ICU) admission, elevated levels of interleukin-6 (IL-6) and D-dimer, and administration of steroids particularly medium-dose steroids. Conclusion Secondary infections can occur within 43 days of COVID-19 infection for every 12.7 per 100 patients in whom there is bacterial or fungal infections. Of these secondary infections, incidence of mucormycosis and sepsis was found to be higher in our study. COVID-19-infected patients who have either of these factors such as elevated inflammatory markers (Il-6 and D-dimer), the presence of comorbidities such as diabetes mellitus and CKD, ICU admission, and the use of steroids are at risk of developing secondary infections. Through proper screening, we can prevent patients who are at risk of developing secondary infections.

Exploring KRAS-mutant pancreatic ductal adenocarcinoma: a model validation study.

Pancreatic ductal adenocarcinoma (PDAC) has the highest mortality rate among all solid tumors. Tumorigenesis is promoted by the oncogene KRAS, and KRAS mutations are prevalent in patients with PDAC. Therefore, a comprehensive understanding of the interactions between KRAS mutations and PDAC may expediate the development of therapeutic strategies for reversing the progression of malignant tumors. Our study aims at establishing and validating a prediction model of KRAS mutations in patients with PDAC based on survival analysis and mRNA expression. A total of 184 and 412 patients with PDAC from The Cancer Genome Atlas (TCGA) database and the International Cancer Genome Consortium (ICGC), respectively, were included in the study. After tumor mutation profile and copy number variation (CNV) analyses, we established and validated a prediction model of KRAS mutations, based on survival analysis and mRNA expression, that contained seven genes: CSTF2, FAF2, KIF20B, AKR1A1, APOM, KRT6C, and CD70. We confirmed that the model has a good predictive ability for the prognosis of overall survival (OS) in patients with KRAS-mutated PDAC. Then, we analyzed differential biological pathways, especially the ferroptosis pathway, through principal component analysis, pathway enrichment analysis, Gene Ontology (GO) enrichment analysis, and gene set enrichment analysis (GSEA), with which patients were classified into low- or high-risk groups. Pathway enrichment results revealed enrichment in the cytokine-cytokine receptor interaction, metabolism of xenobiotics by cytochrome P450, and viral protein interaction with cytokine and cytokine receptor pathways. Most of the enriched pathways are metabolic pathways predominantly enriched by downregulated genes, suggesting numerous downregulated metabolic pathways in the high-risk group. Subsequent tumor immune infiltration analysis indicated that neutrophil infiltration, resting CD4 memory T cells, and resting natural killer (NK) cells correlated with the risk score. After verifying that the seven gene expression levels in different KRAS-mutated pancreatic cancer cell lines were similar to that in the model, we screened potential drugs related to the risk score. This study established, analyzed, and validated a model for predicting the prognosis of PDAC based on risk stratification according to KRAS mutations, and identified differential pathways and highly effective drugs.

MicroRNA750-3p Targets Processing of Precursor 7 to Suppress Rice Black-Streaked Dwarf Virus Propagation in Vector Laodelphax striatellus.

MicroRNAs (miRNAs) are non-coding RNAs, which, as members of the RNA interference pathway, play a pivotal role in antiviral infection. Almost 80% of plant viruses are transmitted by insect vectors; however, little is known about the interaction of the miRNAs of insect vectors with plant viruses. Here, we took rice black-streaked dwarf virus (RBSDV), a devastating virus to rice production in eastern Asia, and the small brown planthopper, (SBPH, Laodelphax striatellus) as a model to investigate the role of microRNA750-3p (miR750-3p) in regulating viral transmission. Our results showed that Ls-miR750-3p was downregulated in RBSDV-infected SBPH and predominately expressed in the midgut of SBPH. Injection with miR750-3p agomir significantly reduced viral accumulation, and the injection with the miR750-3p inhibitor, antagomir-750-3p, dramatically promoted the viral accumulation in SBPH, as detected using RT-qPCR and Western blotting. The processing of precursor 7 (POP7), a subunit of RNase P and RNase MRP, was screened, identified, and verified using a dual luciferase reporter assay as one target of miR750-3p. Knockdown of POP7 notably increased RBSDV viral propagation in SBPH and then increased the viral transmission rate by SBPH. Taken together, our data indicate that miR750-3p targets POP7 to suppress RBSDV infection in its insect vector. These results enriched the role of POP7 in modulating virus infection in host insects and shared new insight into the function of miRNAs in plant virus and insect vector interaction.

Differential microRNA Expression Analysis in Patients with HPV-Infected Ovarian Neoplasms.

This study aimed to identify microRNAs (miRNAs) whose expression levels are altered by high-risk human papillomavirus (HR-HPV) infection in women with epithelial ovarian neoplasms. MiRNA expression was quantified by real-time polymerase chain reaction, while HR-HPV DNA was quantified using digital-droplet PCR. Analysis of 11 miRNAs demonstrated significantly lower hsa-miR-25-5p expression in HPV-infected compared to uninfected ovarian tissues (p = 0.0405), while differences in miRNA expression in corresponding serum were statistically insignificant. The expression of hsa-miR-218-5p in ovarian tumors was significantly higher in high-grade serous ovarian carcinoma (HGSOC) cases than in other neoplasms (p = 0.0166). In addition, hsa-miR-218-5p was significantly upregulated, whereas hsa-miR-191-5p was significantly downregulated in tissues with stage III/IV FIGO (p = 0.0009 and p = 0.0305, respectively). Using unsupervised clustering, we identified three unique patient groups with significantly varied frequencies of HPV16/18-positive samples and varied miRNA expression profiles. In multivariate analysis, high expression of hsa-miR-16-5p was an independent prognostic factor for poor overall survival (p = 0.0068). This preliminary analysis showed the changes in miRNA expression in ovarian neoplasms during HPV infection and those collected from HGSOCs or patients with advanced disease. This prospective study can provide new insights into the pathogenesis of ovarian neoplasms and host-virus interactions.

Study on transcriptome characteristics of respiratory syncytial virus bronchiolitis in children by RNA sequencing

To explore the biological characteristics related to the pathogenesis and severity of respiratory syncytial virus (RSV) bronchiolitis by RNA sequencing of white blood cells in children with RSV bronchiolitis. This study is a case-control study. A total of 87 children diagnosed with bronchiolitis and RSV antigen positive and/or RSV nucleic acid positive in the pediatric respiratory department of the Second Affiliated Hospital of Wenzhou Medical University from October 2019 to April 2022 were selected as the case group. The case group was divided into three groups based on the condition: mild, moderate, and severe, and there were two groups according to the presence or absence of atopic symptoms: the atopic group and the non-atopic group, forty healthy children in the same period were selected as the control group. The whole blood leukocyte RNA of the children in the case group and the control group was extracted for RNA sequencing, and the data were analyzed to obtain differentially expressed genes (DEGs). Then, the immunobiological pathways and genes related to the pathogenesis, disease condition, and atopy were screened through Gene Ontology (GO) annotation, Kyoto Gene and Genome Encyclopedia (KEGG) annotation, and protein interaction network (PPI) construction methods. Construct the weighted gene co-expression network analysis (WGCNA) module to identify potential biological indicators related to disease severity.Compared with the control group, the case group had a total of 1 782 DEGs, including 1 586 upregulated genes and 196 downregulated genes. The GO pathway enrichment of DEGs is mainly enriched in molecular functions such as peroxidase activity and oxidoreductase activity. In the cytological components, it is mainly enriched in cytoplasmic vesicle lumen and secretory granule lumen. In biological processes, it is mainly enriched in processes such as neutrophil activation involved in immune responses, neutrophil degranulation, and neutrophil activation. KEGG analysis is mainly concentrated in the signal pathway of the viral protein interaction with cytokine and cytokine receptor. A PPI network was constructed to screen four genes at the core position, including CCL2, IL-10, MMP9 and JUN. The DEGs obtained by comparing different disease groups with the control group are mainly enriched in retrograde endocannabinoid signaling and cell apoptosis pathways. WGCNA analysis showed that the brown module related to oxygen saturation was most closely related to the disease, and its gene was mainly enriched in the RNA helicase retinoic acid inducible gene-I (RIG-I) like receptor signal pathway. There are 230 specific DEGs in the atopic group and 444 in the non-atopic group. KEGG enrichment analysis results show that both groups are enriched to NF-κB signaling pathway, the characteristic does not cause significant changes in immune response and transcriptome characteristics in children with RSV bronchiolitis. In conclusion, neutrophil activation, degranulation pathway and signal pathway of interaction between viral protein and cytokine and cytokine receptor are involved in the immune response of RSV bronchiolitis host. CCL2, IL-10, MMP9 and JUN genes may be associated with the pathogenesis. They might be potential biomarkers related to disease severity in RIG-I like receptors, cell apoptosis, and endogenous cannabinoid related signaling pathways.

Cell Fractionation and the Identification of Host Proteins Involved in Plant-Virus Interactions.

Plant viruses depend on host cellular factors for their replication and movement. There are cellular proteins that change their localization and/or expression and have a proviral role or antiviral activity and interact with or target viral proteins. Identification of those proteins and their roles during infection is crucial for understanding plant-virus interactions and to design antiviral resistance in crops. Important host proteins have been identified using approaches such as tag-dependent immunoprecipitation or yeast two hybridization that require cloning individual proteins or the entire virus. However, the number of possible interactions between host and viral proteins is immense. Therefore, an alternative method is needed for proteome-wide identification of host proteins involved in host-virus interactions. Here, we present cell fractionation coupled with mass spectrometry as an option to identify protein-protein interactions between viruses and their hosts. This approach involves separating subcellular organelles using differential and/or gradient centrifugation from virus-free and virus-infected cells (1) followed by comparative analysis of the proteomic profiles obtained for each subcellular organelle via mass spectrometry (2). After biological validation, prospect host proteins with proviral or antiviral roles can be subject to fundamental studies in the context of basic biology to shed light on both virus replication and cellular processes. They can also be targeted via gene editing to develop virus-resistant crops.

THE ECOLOGICAL SIGNIFICANCE OF VIRUSES IN AQUATIC ECOSYSTEMS: A COMPREHENSIVE ANALYSIS


 It is widely acknowledged that viruses are essential elements of the aquatic Environment, contributing significantly to various ecological processes and altering the dynamics of aquatic ecosystems. The variety of viruses in aquatic habitats, including freshwater and marine ecosystems, is enormous. Numerous different types of organisms, such as bacteria, algae, protozoa, and even multicellular organisms, are susceptible to these viral interactions, and these organisms have a significant impact on the design and operation of aquatic ecosystems. In aquatic ecosystems, viral-mediated mortality facilitates the recycling of nutrients and energy by influencing the composition of microbial populations. Additionally, viruses participate in genetic transfer procedures and are essential for horizontal gene transfer. They also serve as genetic material carriers, allowing the transfer of genes between various organisms. This phenomenon affects the ecological balance in the aquatic Environment and the evolution and adaption of microbial communities. Viruses can be used as instruments to investigate microbial ecology, comprehend host-virus interactions, and create fresh antiviral tactics. Viruses are essential to the health and stability of aquatic environments. Aquatic viruses have attracted attention because of their potential utility in various sectors, including biotechnology and medical research; they are essential elements of the aquatic environment due to their capacity to control microbial populations, reduce toxic algal blooms, and offer insights into microbial ecology. Our comprehension of these complex interactions and their larger implications for environmental health and management will be improved by additional study and investigation of viral dynamics and interactions within aquatic ecosystems. This review attempts to present an overview of the significance of viruses in aquatic ecosystems by highlighting their variety of roles and interactions.

ETS1 Function in Leukemia and Lymphoma.

ETS proto-oncogene 1 (ETS1) is a transcription factor (TF) critically involved in lymphoid cell development and function. ETS1 expression is tightly regulated throughout differentiation and activation in T-cells, natural killer (NK) cells, and B-cells. It has also been described as an oncogene in a range of solid and hematologic cancer types. Among hematologic malignancies, its role has been best studied in T-cell acute lymphoblastic leukemia (T-ALL), adult T-cell leukemia/lymphoma (ATLL), and diffuse large B-cell lymphoma (DLBCL). Aberrant expression of ETS1 in these malignancies is driven primarily by chromosomal amplification and enhancer-driven transcriptional regulation, promoting the ETS1 transcriptional program. ETS1 also facilitates aberrantly expressed or activated transcriptional complexes to drive oncogenic pathways. Collectively, ETS1 functions to regulate cell growth, differentiation, signaling, response to stimuli, and viral interactions in these malignancies. A tumor suppressor role has also been indicated for ETS1 in select lymphoma types, emphasizing the importance of cellular context in ETS1 function. Research is ongoing to further characterize the clinical implications of ETS1 dysregulation in hematologic malignancies, to further resolve binding complexes and transcriptional targets, and to identify effective therapeutic targeting approaches.

A comprehensive review of Wolbachia-mediated mechanisms to control dengue virus transmission in Aedes aegypti through innate immune pathways.

The Dengue virus (DENV), primarily spread by Aedes aegypti and also by Aedes albopictus in some regions, poses significant global health risks. Alternative techniques are urgently needed because the current control mechanisms are insufficient to reduce the transmission of DENV. Introducing Wolbachia pipientis into Ae. aegypti inhibits DENV transmission, however, the underlying mechanisms are still poorly understood. Innate immune effector upregulation, the regulation of autophagy, and intracellular competition between Wolbachia and DENV for lipids are among the theories for the mechanism of inhibition. Furthermore, mainly three immune pathways Toll, IMD, and JAK/STAT are involved in the host for the suppression of the virus. These pathways are activated by Wolbachia and DENV in the host and are responsible for the upregulation and downregulation of many genes in mosquitoes, which ultimately reduces the titer of the DENV in the host. The functioning of these immune pathways depends upon the Wolbachia, host, and virus interaction. Here, we summarize the current understanding of DENV recognition by the Ae. aegypti's immune system, aiming to create a comprehensive picture of our knowledge. Additionally, we investigated how Wolbachia regulates the activation of multiple genes associated with immune priming for the reduction of DENV.

Effects of Weizhuan'an on rats with precancerous lesions of gastric cancer based on regulating gastric mucosal microflora and inflammatory factors.

This study aimed to observe the intervention of Weizhuan'an prescription on rats with precancerous lesions of gastric cancer (PLGC) as well as its regulation on gastric mucosal microflora and inflammatory factors and explore the pharmacodynamic mechanisms of Weizhuan'an Formula. The rats were classified into the blank control group (BCG); low-, medium-, and high-dose groups of Weizhuan'an prescription (LDG, MDG, and HDG, respectively); and natural recovery group (NRG) at random. The rats in the traditional Chinese medicine (TCM) group were given corresponding doses of Weizhuan'an formula, while the rats in the NRG and BCG were given an equivalent volume of distilled water for 12weeks. After that, gastric mucosa samples of rats were collected to observe the general and pathological changes in the gastric mucosa; the changes in gastric mucosal microflora were detected by 16S rDNA amplicon sequencing, and the inflammatory factors were analyzed by cytokine antibody microarray and Western blotting. The results suggest that compared with the BCG, the pathology of gastric mucosa and gastric mucosal microflora and inflammatory factors in rats with PLGC have changed significantly, while Weizhuan'an formula effectively improved them, especially in the MDG and HDG (p < 0.05). Compared with the NRG, the abundance of probiotics such as Lactobacillus and Veillonella were increased, while the abundance of pathogens such as Proteobacteria and Pseudomonas was decreased (p < 0.05, p < 0.01), and the relative contents of IL-2, IL-4, IL-13, and MCP-1 in gastric mucosa were decreased (p < 0.05). Moreover, it can upregulate the DNA-binding transcriptional regulator, ABC type multidrug transport system, and related enzymes and affect the signaling pathways such as viral protein interaction with cytokine and cytokine receptor and T cell receptor signaling pathway significantly (p < 0.05, p < 0.01), which can promote drug absorption and utilization and repair damaged gastric mucosa. The study confirmed that Weizhuan'an prescription can treat rats with PLGC by regulating gastric mucosal microflora and inflammatory factors.

Application of PolyPRep tools on HIV protease polyproteins using molecular docking.

In recent years, the development of high-throughput technologies for obtaining sequence data leveraged the possibility of analysis of protein data in silico. However, when it comes to viral polyprotein interaction studies, there is a gap in the representation of those proteins, given their size and length. The prepare for studies using state-of-the-art techniques such as Machine Learning, a good representation of such proteins is a must. We present an alternative to this problem, implementing a fragmentation and modeling protocol to prepare those polyproteins in the form of peptide fragments. Such procedure is made by several scripts, implemented together on the workflow we call PolyPRep, a tool written in Python script and available in GitHub. This software is freely available only for noncommercial users.

Mapping the landscape of HPV integration and characterising virus and host genome interactions in HPV-positive oropharyngeal squamous cell carcinoma.

Human papillomavirus (HPV) integration into the host genome is an important factor in HPV(+)OPSCC carcinogenesis, in conjunction with HPV oncoproteins E6/E7. However, a well-studied investigation about virus-host interaction still needs to be completed. Our objective is to characterise HPV integration to investigate potential mechanisms of tumourigenesis independent of E6/E7 oncoproteins. High-throughput viral integration detection was performed on 109 HPV(+)OPSCC tumours with relevant clinicopathological information. Of these tumours, 38 tumours underwent targeted gene sequencing, 29 underwent whole exome sequencing and 26 underwent RNA sequencing. HPV integration was detected in 94% of tumours (with a mean integration count of 337). Tumours occurring at the tonsil/oropharyngeal wall that exhibit higher PD-L1 expression demonstrated increased integration sites (p=.024). HPV exhibited a propensity for integration at genomic sites located within specific fragile sites (FRA19A) or genes associated with functional roles such as cell proliferation and differentiation (PTEN, AR), immune evasion (CD274) and glycoprotein biosynthesis process (FUT8). The viral oncogenes E2, E4, E6 and E7 tended to remain intact. HPV fragments displayed enrichment within host copy number variation (CNV) regions. However, insertions into genes related to altered homologous recombination repair were infrequent. Genes with integration had distinct expression levels. Fifty-nine genes whose expression level was affected by viral integration were identified, for example, EPHB1, which was reported to be involved in cellular protein metabolic process. HPV can promote oncogenesis through recurrent integration into functional host genome regions, leading to subsequent genomic aberrations and gene expression disruption. This study characterises viral integrations and virus-host interactions, enhancing our understanding of HPV-related carcinogenesis mechanisms.

An outbreak of Akabane disease in a cattle herd on the Mughan plain, Iran.

In November 2021, an investigation was conducted into an outbreak of abortion, stillbirth, and the birth of calves with congenital abnormalities (arthrogryposis and hydranencephaly) at a dairy farm in Dasht-e-Mughan city, Ardabil province. A total of 70 cows experienced these issues. To determine the cause of the outbreak, post-mortem brain tissue samples were collected from two calves affected by hydranencephaly, which occurred shortly after their birth. Polymerase chain reaction (PCR) testing was conducted for multiple viruses, including bovine viral diarrhea (BVD), border disease, Akabane, Schmallenberg, and bluetongue viruses (BTVs). The samples were positive only for Akabane virus. Serum samples were collected from a group of 60 cattle, consisting of 45 adult cows and 15 younger calves aged between 8 to 10 months. These samples were analyzed to detect the presence of antibodies against the Akabane and Schmallenberg viruses. Both of these viruses are known to be responsible for causing abortion, stillbirth, and congenital abnormalities in calves. Among 45 cows that tested by competitive enzyme-linked immunosorbent assay (cELISA), 26.66% and 33.33% exhibited antibodies against Akabane and Schmallenberg viruses, respectively. Notably, 20.00% of cows co-exhibited antibodies for both viruses. Despite PCR evidence implicating Akabane virus as the principal etiology of clinical signs observed in the affected herd, the high co-seropositivity to Schmallenberg virus, warrants a thorough investigation into potential viral interactions. Further research is required to determine the source of the virus and their transmission routes. This information could facilitate the refinement of disease control strategies and improving the management of reproductive challenges in such affected herds.