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Journal of Virology Oct 2023African swine fever virus (ASFV) is the cause of the current major animal epidemic worldwide. This disease affects domestic pigs and wild boars, has spread since 2007...
African swine fever virus (ASFV) is the cause of the current major animal epidemic worldwide. This disease affects domestic pigs and wild boars, has spread since 2007 through Russia, Eastern Europe, and more recently to Western European countries, and since 2018 emerged in China, from where it spread throughout Southeast Asia. Recently, outbreaks have appeared in the Caribbean, threatening the Americas. It is estimated that more than 900,000 animals have died directly or indirectly from ASFV since 2021 alone. One of the features of ASFV infection is hemoadsorption (HAD), which has been linked to virulence, although the molecular and pathological basis of this hypothesis remains largely unknown. In this study, we have analyzed and identified the key players responsible of HAD, contributing to the identification of new determinants of ASFV virulence, the understanding of ASFV pathogenesis, and the rational development of new vaccines.
Topics: Animals; African Swine Fever; African Swine Fever Virus; Glycosylation; Hemadsorption; Protein Sorting Signals; Swine; Virulence; Viral Proteins
PubMed: 37768082
DOI: 10.1128/jvi.01030-23 -
Virology Journal Aug 2023SARS-CoV-2 has been responsible for the recent pandemic all over the world, which has caused many complications. One of the hallmarks of SARS-CoV-2 infection is an... (Review)
Review
SARS-CoV-2 has been responsible for the recent pandemic all over the world, which has caused many complications. One of the hallmarks of SARS-CoV-2 infection is an induced immune dysregulation, in some cases resulting in cytokine storm syndrome, acute respiratory distress syndrome and many organs such as lungs, brain, and heart that are affected during the SARS-CoV-2 infection. Several physiological parameters are altered as a result of infection and cytokine storm. Among them, microRNAs (miRNAs) might reflect this poor condition since they play a significant role in immune cellular performance including inflammatory responses. Both host and viral-encoded miRNAs are crucial for the successful infection of SARS-CoV-2. For instance, dysregulation of miRNAs that modulate multiple genes expressed in COVID-19 patients with comorbidities (e.g., type 2 diabetes, and cerebrovascular disorders) could affect the severity of the disease. Therefore, altered expression levels of circulating miRNAs might be helpful to diagnose this illness and forecast whether a COVID-19 patient could develop a severe state of the disease. Moreover, a number of miRNAs could inhibit the expression of proteins, such as ACE2, TMPRSS2, spike, and Nsp12, involved in the life cycle of SARS-CoV-2. Accordingly, miRNAs represent potential biomarkers and therapeutic targets for this devastating viral disease. In the current study, we investigated modifications in miRNA expression and their influence on COVID-19 disease recovery, which may be employed as a therapy strategy to minimize COVID-19-related disorders.
Topics: Humans; COVID-19; Diabetes Mellitus, Type 2; Inflammation; MicroRNAs; SARS-CoV-2; RNA, Viral
PubMed: 37559103
DOI: 10.1186/s12985-023-02152-6 -
International Journal of Molecular... Apr 2024CX3CL1, also named fractalkine or neurotactin, is the only known member of the CX3C chemokine family that can chemoattract several immune cells. CX3CL1 exists in both... (Review)
Review
CX3CL1, also named fractalkine or neurotactin, is the only known member of the CX3C chemokine family that can chemoattract several immune cells. CX3CL1 exists in both membrane-anchored and soluble forms, with each mediating distinct biological activities. CX3CL1 signals are transmitted through its unique receptor, CX3CR1, primarily expressed in the microglia of the central nervous system (CNS). In the CNS, CX3CL1 acts as a regulator of microglia activation in response to brain disorders or inflammation. Recently, there has been a growing interest in the role of CX3CL1 in regulating cell adhesion, chemotaxis, and host immune response in viral infection. Here, we provide a comprehensive review of the changes and function of CX3CL1 in various viral infections, such as human immunodeficiency virus (HIV), SARS-CoV-2, influenza virus, and cytomegalovirus (CMV) infection, to highlight the emerging roles of CX3CL1 in viral infection and associated diseases.
Topics: Chemokine CX3CL1; Humans; Virus Diseases; Animals; COVID-19; SARS-CoV-2; Microglia; CX3C Chemokine Receptor 1
PubMed: 38674036
DOI: 10.3390/ijms25084451 -
IScience Sep 2023Infectious viral particles in bioaerosols generated during laparoscopic surgery place staff and patients at significant risk of infection and contributed to the...
Infectious viral particles in bioaerosols generated during laparoscopic surgery place staff and patients at significant risk of infection and contributed to the postponement of countless surgical procedures during the COVID-19 pandemic causing excess deaths. The implementation of devices that inactivate viral particles from bioaerosols aid in preventing nosocomial viral spread. We evaluated whether electrostatic precipitation (EP) is effective in capturing and inactivating aerosolized enveloped and non-enveloped viruses. Using a closed-system model mimicking release of bioaerosols during laparoscopic surgery, known concentrations of each virus were aerosolized, exposed to EP and collected for analysis. We demonstrate that both enveloped and non-enveloped viral particles were efficiently captured and inactivated by EP, which was enhanced by increasing the voltage to 10 kV or using two discharge electrodes together at 8 kV. This study highlights EP as an effective means for capturing and inactivating viral particles in bioaerosols, which may enable continued surgical procedures during future pandemics.
PubMed: 37664619
DOI: 10.1016/j.isci.2023.107567 -
Journal of Nanobiotechnology May 2024Nanobodies, single-domain antibodies derived from variable domain of camelid or shark heavy-chain antibodies, have unique properties with small size, strong binding... (Review)
Review
Nanobodies, single-domain antibodies derived from variable domain of camelid or shark heavy-chain antibodies, have unique properties with small size, strong binding affinity, easy construction in versatile formats, high neutralizing activity, protective efficacy, and manufactural capacity on a large-scale. Nanobodies have been arisen as an effective research tool for development of nanobiotechnologies with a variety of applications. Three highly pathogenic coronaviruses (CoVs), SARS-CoV-2, SARS-CoV, and MERS-CoV, have caused serious outbreaks or a global pandemic, and continue to post a threat to public health worldwide. The viral spike (S) protein and its cognate receptor-binding domain (RBD), which initiate viral entry and play a critical role in virus pathogenesis, are important therapeutic targets. This review describes pathogenic human CoVs, including viral structures and proteins, and S protein-mediated viral entry process. It also summarizes recent advances in development of nanobodies targeting these CoVs, focusing on those targeting the S protein and RBD. Finally, we discuss potential strategies to improve the efficacy of nanobodies against emerging SARS-CoV-2 variants and other CoVs with pandemic potential. It will provide important information for rational design and evaluation of therapeutic agents against emerging and reemerging pathogens.
Topics: Single-Domain Antibodies; Humans; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Animals; COVID-19; Coronavirus Infections; Middle East Respiratory Syndrome Coronavirus; Virus Internalization; Pandemics; Betacoronavirus; Antibodies, Viral; Pneumonia, Viral; Severe acute respiratory syndrome-related coronavirus; Antibodies, Neutralizing
PubMed: 38822339
DOI: 10.1186/s12951-024-02573-7 -
MSphere Oct 2023Single-cell RNA-seq has been used to characterize human COVID-19. To determine if preclinical models successfully mimic the cell-intrinsic and -extrinsic effects of... (Meta-Analysis)
Meta-Analysis
Single-cell RNA-seq has been used to characterize human COVID-19. To determine if preclinical models successfully mimic the cell-intrinsic and -extrinsic effects of severe disease, we conducted a meta-analysis of single-cell data across five model species. To assess whether dissemination of viral RNA in lung cells tracks pathology and results in cell-intrinsic and -extrinsic transcriptomic changes in COVID-19. We conducted a meta-analysis by analyzing six publicly available, scRNA-seq data sets. We used dual mapping (host and virus) and differential gene expression analyses to compare viral and viral cell populations. We conducted a principal component analysis to identify successful models of human COVID-19. We found expression of viral RNA in many non-epithelial cell types. Fibroblasts, macrophages, and endothelial cells exhibit clear evidence of viral-intrinsic and -extrinsic effects on host gene expression. Using viral RNA expression, we found that K18-hACE2 mice most closely modeled severe human COVID-19, followed by hamsters. Ferrets and macaques are poor models of human disease due to the low presence of viral RNA. Moreover, we found that increased transcripts of certain key inflammatory genes such as , and are not restricted to virally infected cells, suggesting these genes are regulated in a paracrine or autocrine fashion. These data affirm widespread dissemination of viral RNA in the lung, which may be key in the pathogenesis of severe COVID-19 and demonstrate ferrets and Rhesus macaques are poor models of human COVID-19. IMPORTANCE We conducted a high-resolution meta-analysis of scRNA-seq data from humans and five animal models of COVID-19. This study reports viral RNA dissemination in several cell types in human data as well as in some of the pre-clinical models. Using this metric, the K18-hACE2 mouse model, followed by the hamster model, most closely resembled human COVID-19. We observed clear evidence of viral-intrinsic effects within cells (e.g., expression) as well as viral-extrinsic cytokine modulation (e.g., ). We observed proinflammatory chemokine expression in cells devoid of viral RNA expression, suggesting autocrine/paracrine interferon regulation. This report serves as a resource-synthesizing data from COVID-19 humans and animal models and suggesting improvements for relevant pre-clinical models that may aid future diagnostic and therapeutic development projects.
Topics: Cricetinae; Humans; Animals; Mice; RNA, Viral; SARS-CoV-2; Endothelial Cells; Ferrets; Interleukin-18; Macaca mulatta; COVID-19
PubMed: 37737611
DOI: 10.1128/msphere.00375-23 -
Clinical and Experimental Medicine May 2024The ubiquitous RNA-processing molecule TDP-43 is involved in neuromuscular diseases such as inclusion body myositis, a late-onset acquired inflammatory myopathy. TDP-43... (Review)
Review
The ubiquitous RNA-processing molecule TDP-43 is involved in neuromuscular diseases such as inclusion body myositis, a late-onset acquired inflammatory myopathy. TDP-43 solubility and function are disrupted in certain viral infections. Certain viruses, high viremia, co-infections, reactivation of latent viruses, and post-acute expansion of cytotoxic T cells may all contribute to inclusion body myositis, mainly in an age-shaped immune landscape. The virally induced senescent, interferon gamma-producing cytotoxic CD8+ T cells with increased inflammatory, and cytotoxic features are involved in the occurrence of inclusion body myositis in most such cases, in a genetically predisposed host. We discuss the putative mechanisms linking inclusion body myositis, TDP-43, and viral infections untangling the links between viruses, interferon, and neuromuscular degeneration could shed a light on the pathogenesis of the inclusion body myositis and other TDP-43-related neuromuscular diseases, with possible therapeutic implications.
Topics: Myositis, Inclusion Body; Humans; Virus Diseases; DNA-Binding Proteins
PubMed: 38693436
DOI: 10.1007/s10238-024-01353-9 -
Journal of Virology Nov 2023The infectious bursal disease virus is still an important agent which largely threatens global poultry farming industry economics. VP3 is a multifunctional scaffold...
The infectious bursal disease virus is still an important agent which largely threatens global poultry farming industry economics. VP3 is a multifunctional scaffold structural protein that is involved in virus morphogenesis and the regulation of diverse cellular signaling pathways. However, little is known about the roles of VP3 phosphorylation during the IBDV life cycle. In this study, we determined that IBDV infection induced the upregulation of Cdc7 expression and phosphorylated the VP3 Ser13 site to promote viral replication. Moreover, we confirmed that the negative charge addition of phosphoserine on VP3 at the S13 site was essential for IBDV proliferation. This study provides novel insight into the molecular mechanisms of VP3 phosphorylation-mediated regulation of IBDV replication.
Topics: Animals; Avibirnavirus; Birnaviridae Infections; Capsid Proteins; Cell Cycle Proteins; Chickens; Infectious bursal disease virus; Phosphorylation; Protein Serine-Threonine Kinases; Viral Structural Proteins; Virus Replication
PubMed: 37902398
DOI: 10.1128/jvi.01125-23 -
Gene Therapy May 2024In this study, we demonstrate the safety and utility of CRISPR-Cas9 gene editing technology for in vivo editing of proviral DNA in ART-treated, virally controlled simian...
In this study, we demonstrate the safety and utility of CRISPR-Cas9 gene editing technology for in vivo editing of proviral DNA in ART-treated, virally controlled simian immunodeficiency virus (SIV) infected rhesus macaques, an established model for HIV infection. EBT-001 is an AAV9-based vector delivering SaCas9 and dual guide RNAs designed to target multiple regions of the SIV genome: the viral LTRs, and the Gag gene. The results presented here demonstrate that a single IV inoculation of EBT-001 at each of 3 dose levels (1.4 × 10, 1.4 × 10 and 1.4 × 10 genome copies/kg) resulted in broad and functional biodistribution of AAV9-EBT-001 to known tissue reservoirs of SIV. No off-target effects or abnormal pathology were observed, and animals returned to their normal body weight after receiving EBT-001. Importantly, the macaques that received the 2 highest doses of EBT-001 showed improved absolute lymphocyte counts as compared to antiretroviral-treated controls. Taken together, these results demonstrate safety, biodistribution, and in vivo proviral DNA editing following IV administration of EBT-001, supporting the further development of CRISPR-based gene editing as a potential therapeutic approach for HIV in humans.
Topics: Animals; Simian Immunodeficiency Virus; Macaca mulatta; Gene Editing; CRISPR-Cas Systems; Simian Acquired Immunodeficiency Syndrome; Tissue Distribution; Genetic Vectors; Genetic Therapy; Dependovirus
PubMed: 37587230
DOI: 10.1038/s41434-023-00410-4 -
Virus Genes Aug 2023Human metapneumovirus (HMPV) is a major pathogen of acute respiratory tract infections (ARTIs) in children. Whole genome sequence analyses could help understand the...
Human metapneumovirus (HMPV) is a major pathogen of acute respiratory tract infections (ARTIs) in children. Whole genome sequence analyses could help understand the evolution and transmission events of this virus. In this study, we sequenced HMPV whole genomes to improve the identification of molecular epidemiology in Beijing, China. Nasopharyngeal aspirates of hospitalized children aged < 14 years old with ARTIs were screened for HMPV infection using qPCR. Fourteen pairs of overlapping primers were used to amplify whole genome sequences of HMPV from positive samples with high viral loads. The epidemiology of HMPV was analysed and 27 HMPV whole genome sequences were obtained. Sequence identity and the positional entropy analyses showed that most regions of HMPV genome are conserved, whereas the G gene contained many variations. Phylogenetic analysis identified 25 HMPV sequences that belonged to a newly defined subtype A2b1; G gene sequences from 24 of these contained a 111-nucleotide duplication. HMPV is an important respiratory pathogen in paediatric patients. The new subtype A2b1 with a 111-nucleotide duplication has become predominate in Beijing, China.
Topics: Whole Genome Sequencing; Metapneumovirus; Evolution, Molecular; Humans; Male; Female; Infant; Child, Preschool; Child; Adolescent; Paramyxoviridae Infections; Phylogeny
PubMed: 37150780
DOI: 10.1007/s11262-023-02001-2