99,940 results match your criteria host viral

Placental expression of ACE2 and TMPRSS2 in maternal SARS-CoV-2 infection: are placental defenses mediated by fetal sex?

J Infect Dis 2021 Jul 22. Epub 2021 Jul 22.

Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Background: Sex differences in vulnerability to and severity of SARS-CoV-2 infection have been described in non-pregnant populations. ACE2 and TMPRSS2, host molecules required for viral entry, are regulated by sex steroids and expressed in the placenta. We sought to investigate whether placental ACE2 and TMPRSS2 expression vary by fetal sex and in the presence of maternal SARS-CoV-2 infection. Read More

View Article and Full-Text PDF

A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site.

PLoS Pathog 2021 Jul 22;17(7):e1009671. Epub 2021 Jul 22.

Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia, United States of America.

Allosteric integrase inhibitors (ALLINIs) are a class of experimental anti-HIV agents that target the noncatalytic sites of the viral integrase (IN) and interfere with the IN-viral RNA interaction during viral maturation. Here, we report a highly potent and safe pyrrolopyridine-based ALLINI, STP0404, displaying picomolar IC50 in human PBMCs with a >24,000 therapeutic index against HIV-1. X-ray structural and biochemical analyses revealed that STP0404 binds to the host LEDGF/p75 protein binding pocket of the IN dimer, which induces aberrant IN oligomerization and blocks the IN-RNA interaction. Read More

View Article and Full-Text PDF

Inhalable nanocatchers for SARS-CoV-2 inhibition.

Proc Natl Acad Sci U S A 2021 Jul 2;118(29). Epub 2021 Jul 2.

Institute of Functional Nano and Soft Materials, Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou 215123, China;

The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2), presents an urgent health crisis. More recently, an increasing number of mutated strains of SARS-CoV-2 have been identified globally. Such mutations, especially those on the spike glycoprotein to render its higher binding affinity to human angiotensin-converting enzyme II (hACE2) receptors, not only resulted in higher transmission of SARS-CoV-2 but also raised serious concerns regarding the efficacies of vaccines against mutated viruses. Read More

View Article and Full-Text PDF

DIA-Based Proteome Profiling of Nasopharyngeal Swabs from COVID-19 Patients.

J Proteome Res 2021 Jul 22. Epub 2021 Jul 22.

Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street Southwest, Rochester, Minnesota 55905, United States.

Since the recent outbreak of COVID-19, there have been intense efforts to understand viral pathogenesis and host immune response to combat SARS-CoV-2. It has become evident that different host alterations can be identified in SARS-CoV-2 infection based on whether infected cells, animal models or clinical samples are studied. Although nasopharyngeal swabs are routinely collected for SARS-CoV-2 detection by RT-PCR testing, host alterations in the nasopharynx at the proteomic level have not been systematically investigated. Read More

View Article and Full-Text PDF

Sepsis in patients hospitalized with coronavirus disease 2019: how often and how severe?

Curr Opin Crit Care 2021 Jul 20. Epub 2021 Jul 20.

Anesthesiology, Pain and Intensive Care Medicine Department, Federal University of São Paulo, São Paulo, Brazil.

Purpose Of Review: To discuss why severe COVID-19 should be considered sepsis and how co-infection and secondary infection can aggravate this condition and perpetuate organ dysfunction leading to high mortality rates.

Recent Findings: In severe COVID-19, there is both direct viral toxicity and dysregulated host response to infection. Although both coinfection and/or secondary infection are present, the latest is of greater concern mainly in resource-poor settings. Read More

View Article and Full-Text PDF

Inhibition of Measles Viral Fusion Is Enhanced by Targeting Multiple Domains of the Fusion Protein.

ACS Nano 2021 Jul 22. Epub 2021 Jul 22.

Center for Host-Pathogen Interaction, Columbia University Vagelos College of Physicians and Surgeons, New York, New York 10032, United States.

Measles virus (MeV) infection remains a significant public health threat despite ongoing global efforts to increase vaccine coverage. As eradication of MeV stalls, and vulnerable populations expand, effective antivirals against MeV are in high demand. Here, we describe the development of an antiviral peptide that targets the MeV fusion (F) protein. Read More

View Article and Full-Text PDF

Enzymatic assays to explore viral mRNA capping machinery.

Chembiochem 2021 Jul 22. Epub 2021 Jul 22.

University of Warsaw, Centre of New Technologies, Banacha 2c, 02 097, Warsaw, POLAND.

In eukaryotes, mRNA is modified by the addition of the 7-methylguanosine (m7G) 5' cap to protect mRNA from premature degradation, thereby enhancing translation and enabling differentiation between self (endogenous) and non-self RNAs (e.g., viral ones). Read More

View Article and Full-Text PDF

Extracellular Vesicles as a Means of Viral Immune Evasion, CNS Invasion, and Glia-Induced Neurodegeneration.

Front Cell Neurosci 2021 5;15:695899. Epub 2021 Jul 5.

Neuroscience Program, Brain Institute, Tulane University, New Orleans, LA, United States.

Extracellular vesicles (EVs) are small, membrane-bound vesicles released by cells as a means of intercellular communication. EVs transfer proteins, nucleic acids, and other biologically relevant molecules from one cell to another. In the context of viral infections, EVs can also contain viruses, viral proteins, and viral nucleic acids. Read More

View Article and Full-Text PDF

An Aerolysin-like Pore-Forming Protein Complex Targets Viral Envelope to Inactivate Herpes Simplex Virus Type 1.

J Immunol 2021 Jul 21. Epub 2021 Jul 21.

Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Science/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China;

Because most of animal viruses are enveloped, cytoplasmic entry of these viruses via fusion with cellular membrane initiates their invasion. However, the strategies in which host cells counteract cytoplasmic entry of such viruses are incompletely understood. Pore-forming toxin aerolysin-like proteins (ALPs) exist throughout the animal kingdom, but their functions are mostly unknown. Read More

View Article and Full-Text PDF

Hepatitis B virus compartmentalization and single-cell differentiation in hepatocellular carcinoma.

Life Sci Alliance 2021 Sep 21;4(9). Epub 2021 Jul 21.

Université de Strasbourg, Inserm, Institut de Recherche sur Les Maladies Virales et Hépatiques UMR_S1110, Strasbourg, France

Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC) world-wide. The molecular mechanisms of viral hepatocarcinogenesis are still partially understood. Here, we applied two complementary single-cell RNA-sequencing protocols to investigate HBV-HCC host cell interactions at the single cell level of patient-derived HCC. Read More

View Article and Full-Text PDF
September 2021

Quantitative Proteomics Reveals a Novel Role of the E3 Ubiquitin-Protein Ligase FANCL in the Activation of the Innate Immune Response through Regulation of TBK1 Phosphorylation during Peste des Petits Ruminants Virus Infection.

J Proteome Res 2021 Jul 21. Epub 2021 Jul 21.

State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu 730046, PR China.

Peste des petits ruminants virus (PPRV) infection causes considerable innate immunosuppression in its host, which promotes viral replication. However, how the host rescues the innate immune response to counteract this immunosuppression during viral replication remains largely unknown. To explore the mechanisms of how a host counteracts PPRV-mediated innate immunosuppression, a high-throughput quantitation proteomic approach (isobaric tags for relative and absolute quantitation in conjunction with LC-MS/MS) was used to investigate the proteome landscape of goat fetal fibroblasts (GFFs) in response to PPRV infection. Read More

View Article and Full-Text PDF

Inter-subject variation in ACE2 protein expression in human airway epithelia and its relationship to SARS-CoV-2 infection.

J Infect Dis 2021 Jul 21. Epub 2021 Jul 21.

Department of Pediatrics and Microbiology and Immunology, University of Iowa, Iowa City, IA, 52242, USA.

SARS-CoV-2 initiates entry into airway epithelia by binding its receptor, ACE2. To explore whether inter-individual variation in ACE2 abundance contributes to variability in COVID-19 outcomes, we measured ACE2 protein abundance in primary airway epithelial cultures derived from 58 human donor lungs. We found no evidence for sex- or age-dependent differences in ACE2 protein expression. Read More

View Article and Full-Text PDF

Gene therapy for hemophilia: Current status and laboratory consequences.

Int J Lab Hematol 2021 Jul;43 Suppl 1:117-123

Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.

Since the cloning and characterization of the factor VIII (FVIII) and factor IX genes in the mid-1980s, gene therapy has been perceived as having significant potential for the treatment of severe hemophilia. Now, some 35 years later, these proposals are close to being realized through the licensing of the first clinical gene therapy product. Adeno-associated viral vector-mediated gene therapy for hemophilia A and B has been extensively investigated in preclinical models over the past 20 years, and since 2011, there has been increasing evidence in early phase clinical trials that this therapeutic strategy can provide safe and effective rescue of the hemostatic phenotype in severe hemophilia. Read More

View Article and Full-Text PDF

Structural insights into the distinctive RNA recognition and therapeutic potentials of RIG-I-like receptors.

Med Res Rev 2021 Jul 21. Epub 2021 Jul 21.

Department of Molecular Science and Technology, Ajou University, Suwon, Korea.

RNA viruses, including the coronavirus, develop a unique strategy to evade the host immune response by interrupting the normal function of cytosolic retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs). RLRs rapidly detect atypical nucleic acids, thereby triggering the antiviral innate immune signaling cascade and subsequently activates the interferons transcription and induction of other proinflammatory cytokines and chemokines. Nonetheless, these receptors are manipulated by viral proteins to subvert the host immune system and sustain the infectivity and replication potential of the virus. Read More

View Article and Full-Text PDF

Pathogen-induced inflammation is attenuated by the iminosugar MON-DNJ via modulation of the unfolded protein response.

Immunology 2021 Jul 20. Epub 2021 Jul 20.

Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.

Sepsis is a life-threatening condition involving a dysregulated immune response to infectious agents that causes injury to host tissues and organs. Current treatments are limited to early administration of antibiotics and supportive care. While appealing, the strategy of targeted inhibition of individual molecules in the inflammatory cascade has not proved beneficial. Read More

View Article and Full-Text PDF

Comparison of Lethal and Nonlethal Mouse Models of Infection Reveals T-Cell Population-Associated Cytokine Signatures Correlated with Lethality and Protection.

Trop Med Infect Dis 2021 Jul 2;6(3). Epub 2021 Jul 2.

Department of Viral and Rickettsial Diseases, Naval Medical Research Center, Silver Spring, MD 20910, USA.

The antigenic diversity of as well as the interstrain difference(s) associated with virulence in mice impose the necessity to dissect the host immune response. In this study we compared the host response in lethal and non-lethal murine models of infection using the two strains, Karp (New Guinea) and Woods (Australia). The models included the lethal model: Karp intraperitoneal (IP) challenge; and the nonlethal models: Karp intradermal (ID), Woods IP, and Woods ID challenges. Read More

View Article and Full-Text PDF

Cells Stimulated with More Than One Toll-Like Receptor-Ligand in the Presence of a MyD88 Inhibitor Augmented Interferon- via MyD88-Independent Signaling Pathway.

Viral Immunol 2021 Jul 20. Epub 2021 Jul 20.

Department of Bacteriology, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.

Host exposure to pathogens engage multiple pathogen recognition receptors (PRRs) including toll-like receptors (TLRs); recruit intracellular signaling adaptor proteins primarily myeloid differentiation primary response protein 88 (MyD88) for activating downstream signaling cascades, which culminate in the production of type I interferons (IFNs), proinflammatory cytokines, and chemokines; and impede pathogen replication and dissemination. However, recent studies highlight that absence of MyD88 increased antiviral type I IFN induction, and MyD88 mice showed a higher survival rate compared with the low survival rate of the MyD88 mice, implicating MyD88 limits antiviral type I IFN response. As a single infectious agent may harbor multiple PRR agonists, which trigger different sets of TLR-initiated immune signaling, we examined whether MyD88 inhibition during stimulation of cells with more than one TLR-ligand would augment type I IFN. Read More

View Article and Full-Text PDF

Porcine Haemagglutinating Encephalomyelitis Virus Triggers Neural Autophagy Independent of ULK1.

J Virol 2021 Jul 21:JVI0085121. Epub 2021 Jul 21.

Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China.

Uncoordinated 51-like kinase 1 (ULK1) is a well-characterized initiator of canonical autophagy under basal or pathological conditions. Porcine haemagglutinating encephalomyelitis virus (PHEV), a neurotropic betacoronavirus (β-CoV), impairs ULK1 kinase but hijacks autophagy to facilitate viral proliferation. However, the machinery of PHEV-induced autophagy initiation upon ULK1 kinase deficiency remains unclear. Read More

View Article and Full-Text PDF

RNA Helicase DDX17 inhibits Hepatitis B Virus Replication by Blocking Viral Pregenomic RNA Encapsidation.

J Virol 2021 Jul 21:JVI0044421. Epub 2021 Jul 21.

Department of Microbiology and Immunology, Indiana University School of Medicine Indianapolis, IN, USA.

DDX17 is a member of the DEAD-Box helicase family proteins involved in cellular RNA folding, splicing, and translation. It has been reported that DDX17 serves as a co-factor of host zinc finger antiviral protein (ZAP)-mediated retroviral RNA degradation and exerts direct antiviral function against Raft Valley Fever Virus though binding to specific stem-loop structures of viral RNA. Intriguingly, we have previously shown that ZAP inhibits Hepatitis B virus (HBV) replication through promoting viral RNA decay, and the ZAP-responsive element (ZRE) of HBV pregenomic RNA (pgRNA) contains a stem-loop structure, specifically epsilon, which serves as the packaging signal for pgRNA encapsidation. Read More

View Article and Full-Text PDF

Targeted Long-Read Sequencing Reveals Comprehensive Architecture, Burden and Transcriptional Signatures from HBV-Associated Integrations and Translocations in HCC Cell Lines.

J Virol 2021 Jul 21:JVI0029921. Epub 2021 Jul 21.

Gilead Sciences Inc., Foster City, California, USA.

Hepatitis B virus (HBV) can integrate into the chromosomes of infected hepatocytes, creating potentially oncogenic lesions that can lead to hepatocellular carcinoma (HCC). However, our current understanding of integrated HBV DNA architecture, burden and transcriptional activity is incomplete due to technical limitations. A combination of genomics approaches was used to describe HBV integrations and corresponding transcriptional signatures in three HCC cell lines: huH-1, PLC/PRF/5 and Hep3B. Read More

View Article and Full-Text PDF

Structural Insight into the Interaction of Sendai Virus C Protein with Alix To Stimulate Viral Budding.

J Virol 2021 Jul 21:JVI0081521. Epub 2021 Jul 21.

Department of Virology, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.

The Sendai virus (SeV), belonging to the genus of the family , harbors an accessory protein, named C protein, which facilitates the viral pathogenicity in mice. In addition, the C protein is known to stimulate the budding of virus-like particles through the binding to the host ALG-2 interacting protein X (Alix), a component of the endosomal sorting complexes required for transport (ESCRT) machinery. However, siRNA-mediated gene knockdown studies suggested that neither Alix nor C protein are related to the SeV budding. Read More

View Article and Full-Text PDF

EGR1 suppresses porcine epidemic diarrhea virus replication by regulating IRAV to degrade viral nucleocapsid protein.

J Virol 2021 Jul 21:JVI0064521. Epub 2021 Jul 21.

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, PR China.

Porcine epidemic diarrhea virus (PEDV) is a globally distributed alphacoronavirus that has re-emerged lately, resulting in large economic losses. During viral infection, interferon (IFN-I) plays a vital role in the antiviral innate immunity. However, PEDV has evolved strategies to limit IFN-I production. Read More

View Article and Full-Text PDF

LncRNA IFITM4P regulates host antiviral responses by acting as a ceRNA.

J Virol 2021 Jul 21:JVI0027721. Epub 2021 Jul 21.

Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China.

Long noncoding RNAs (lncRNAs) are involved in numerous cellular processes. Increasing evidence suggests that some lncRNAs function in immunity through various complex mechanisms. However, implication of a large fraction of lncRNAs in antiviral innate immunity remains uncharacterized. Read More

View Article and Full-Text PDF

Orf virus ORF120 protein positively regulates the NF-κB pathway by interacting with G3BP1.

J Virol 2021 Jul 21:JVI0015321. Epub 2021 Jul 21.

Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China.

Orf virus (ORFV) is a highly epitheliotropic parapoxvirus with zoonotic significance that induces proliferative lesions in the skin of sheep, goats and humans. Several viral proteins encoded by ORFV, including NF-κB inhibitors, play important roles in hijacking host-associated proteins for viral evasion of the host innate immune response. However, the roles of proteins with unknown functions in viral replication and latent infection remain to be explored. Read More

View Article and Full-Text PDF

Characterisation of a novel ACE2-based therapeutic with enhanced rather than reduced activity against SARS-CoV-2 variants.

J Virol 2021 Jul 21:JVI0068521. Epub 2021 Jul 21.

Autolus Limited, The MediaWorks, 191 Wood Lane, London, W12 7FP.

The human angiotensin-converting enzyme 2 acts as the host cell receptor for SARS-CoV-2 and the other members of the family SARS-CoV-1 and HCoV-NL63. Here we report the biophysical properties of the SARS-CoV-2 spike variants D614G, B.1. Read More

View Article and Full-Text PDF

Porcine circovirus 2 manipulates PERK-ERO1α axis of endoplasmic reticulum in favor of its replication by derepressing viral DNA from HMGB1 sequestration within nuclei.

J Virol 2021 Jul 21:JVI0100921. Epub 2021 Jul 21.

Institute of Preventive Veterinary Medicine and Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, Zhejiang University, Hangzhou, Zhejiang, CHINA.

Porcine circovirus type 2 (PCV2) causes several disease syndromes in grower pigs. PCV2 infection triggers endoplasmic reticulum (ER) stress, autophagy and oxidative stress, all of which support PCV2 replication. We have recently reported that nuclear HMGB1 is an anti-PCV2 factor by binding to viral genomic DNA. Read More

View Article and Full-Text PDF

RaFAH: Host prediction for viruses of Bacteria and Archaea based on protein content.

Patterns (N Y) 2021 Jul 15;2(7):100274. Epub 2021 Jun 15.

Evolutionary Genomics Group, Departamento de Producción Vegetal y Microbiología, Universidad Miguel Hernández, Aptdo. 18., Ctra. Alicante-Valencia N-332, s/n, San Juan de Alicante, 03550 Alicante, Spain.

Culture-independent approaches have recently shed light on the genomic diversity of viruses of prokaryotes. One fundamental question when trying to understand their ecological roles is: which host do they infect? To tackle this issue we developed a machine-learning approach named Random Forest Assignment of Hosts (RaFAH), that uses scores to 43,644 protein clusters to assign hosts to complete or fragmented genomes of viruses of Archaea and Bacteria. RaFAH displayed performance comparable with that of other methods for virus-host prediction in three different benchmarks encompassing viruses from RefSeq, single amplified genomes, and metagenomes. Read More

View Article and Full-Text PDF

Time-of-addition and Temperature-shift Assays to Determine Particular Step(s) in the Viral Life Cycle that is Blocked by Antiviral Substance(s).

Bio Protoc 2018 May 5;8(9):e2830. Epub 2018 May 5.

Department of International Health, Graduate School of Health Sciences, Kobe University, Kobe, Japan.

Viruses infect their host cells to produce progeny virus particles through the sequential steps of the viral life cycle, such as viral attachment, entry, penetration and post-entry events. This protocol describes time-of-addition and temperature-shift assays that are employed to explore which step(s) in the viral life cycle is blocked by an antiviral substance(s). Read More

View Article and Full-Text PDF

Metal-tagging Transmission Electron Microscopy for Localisation of Tombusvirus Replication Compartments in Yeast.

Bio Protoc 2018 Apr 20;8(8):e2822. Epub 2018 Apr 20.

Cell Structure Laboratory, National Center for Biotechnology, CNB-CSIC, campus UAM, Cantoblanco, Madrid, Spain.

Positive-stranded (+) RNA viruses are intracellular pathogens in humans, animals and plants. To build viral replicase complexes (VRCs) viruses manipulate lipid flows and reorganize subcellular membranes. Redesigned membranes concentrate viral and host factors and create an environment that facilitates the formation of VRCs within replication organelles. Read More

View Article and Full-Text PDF