A5051176579- Viral Infections and Outbreaks Research
- Viral Infections and Vectors
- Hepatitis B Virus Studies
- Hepatitis C virus research
- Monoclonal and Polyclonal Antibodies Research
- Mosquito-borne diseases and control
- Viral Infections and Immunology Research
- Animal Disease Management and Epidemiology
- Viral gastroenteritis research and epidemiology
- HIV Research and Treatment
- Respiratory viral infections research
- Animal Virus Infections Studies
- SARS-CoV-2 and COVID-19 Research
- Viral Infectious Diseases and Gene Expression in Insects
- Plant Virus Research Studies
- Virology and Viral Diseases
- Disaster Response and Management
- Bacterial Infections and Vaccines
- Virus-based gene therapy research
- Vector-Borne Animal Diseases
- HIV/AIDS drug development and treatment
- COVID-19 epidemiological studies
- Pneumonia and Respiratory Infections
- interferon and immune responses
- Endoplasmic Reticulum Stress and Disease
Centers for Disease Control and Prevention
2015-2024
National Center for Emerging and Zoonotic Infectious Diseases
2015-2024
United States Department of Health and Human Services
2021
Government of the United States of America
2019
Global Viral
2015-2016
Médecins Sans Frontières
2015
National Center for Immunization and Respiratory Diseases
2015
International Rescue Committee
2015
Ministry of Health
2015
Médecins Sans Frontières
2015
HIV pseudotypes bearing native hepatitis C virus (HCV) glycoproteins (strain H and Con1) are infectious for the human hepatoma cell lines Huh-7 PLC/PR5. Infectivity depends on coexpression of both E1 E2 glycoproteins, is pH-dependent, can be neutralized by mAbs mapping to amino acids 412–447 within E2. Cell-surface expression one or all candidate receptor molecules (CD81, low-density lipoprotein receptor, scavenger class B type 1, dendritic cell-specific intercellular adhesion molecule 3...
ABSTRACT A truncated soluble form of the hepatitis C virus E2 glycoprotein, 661 , binds specifically to surface cells expressing human CD81 (hCD81) but not other members tetraspanin family (CD9, CD63, and CD151). No differences were noted between level binding hCD81 expressed on rat RBL or KM3 compared Daudi Molt-4 cells, suggesting that additional human-cell-specific factors are required for primary interaction with cell surface. did interact African green monkey (AGM) COS which differs...
Abstract GS-5734 is a monophosphate prodrug of an adenosine nucleoside analog that showed therapeutic efficacy in non-human primate model Ebola virus infection. It has been administered under compassionate use to two patients, both whom survived, and currently Phase 2 clinical development for treatment disease. Here we report the antiviral activities parent across multiple families, providing evidence support new indications this compound against human viruses significant public health concern.
The 2013–2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of (EBOV). Early in epidemic, genome sequencing provided insights into evolution and transmission offered important information for outbreak response. Here, we analyze sequences from 232 patients sampled over 7 months Sierra Leone, along with 86 previously released genomes earlier epidemic. We confirm sustained human-to-human within Leone find no evidence import or export EBOV across national borders after its...
ABSTRACT Human CD81 has been previously identified as the putative receptor for hepatitis C virus envelope glycoprotein E2. The large extracellular loop (LEL) of human differs in four amino acid residues from that African green monkey (AGM), which does not bind We mutated each positions to corresponding AGM and expressed them soluble fusion LEL proteins bacteria or complete membrane mammalian cells. found 186 be critical interaction with viral glycoprotein. This residue was also important...
ABSTRACT Hepatitis C virus (HCV) entry is dependent on CD81. To investigate whether the CD81 sequence a determinant of HCV host range, we expressed panel diverse proteins and tested their ability to interact with HCV. large extracellular loop (LEL) sequences were as recombinant proteins; human and, low level, African green monkey bound soluble E2 (sE2) inhibited infection by retrovirus pseudotype particles bearing glycoproteins (HCVpp). In contrast, mouse or rat failed bind sE2 inhibit HCVpp...
ABSTRACT Hepatitis C virus (HCV) glycoproteins E1 and E2, when expressed in eukaryotic cells, are retained the endoplasmic reticulum (ER). C-terminal truncation of E2 at residue 661 or 715 (position on polyprotein) leads to secretion, consistent with deletion a proposed hydrophobic transmembrane anchor sequence. We demonstrate cell surface expression chimeric glycoprotein consisting residues 384 fused cytoplasmic domains influenza A hemagglutinin (HA), termed -HA TMCT . The was able bind...
The primary 2A/2B polyprotein cleavage of aphtho-and cardioviruses is mediated by their 2A proteins cleaving C-terminally. Whilst the aphthovirus region only 16 aa (possibly 18 aa) long, cardiovirus protein some 150 aa. We have previously shown that foot-and-mouth disease virus (FMDV) able to mediate in an artificial (chloramphenicol acetyltransferase/FMDV 2A/beta-glucuronidase [CAT-2A-GUS]) system devoid any other FMDV sequences with high (approximately 85%), although not complete,...
ABSTRACT We recently reported that retroviral pseudotypes bearing the hepatitis C virus (HCV) strain H and Con1 glycoproteins, genotype 1a 1b, respectively, require CD81 as a coreceptor for virus-cell entry infection. Soluble truncated E2 cloned from number of diverse HCV genotypes fail to interact with CD81, suggesting viruses origin may utilize different receptors display altered cell tropism. have used pseudotyping system study tropism glycoproteins. Viruses these glycoproteins showed...
The Clostridium difficile toxins A and B are primarily responsible for symptoms of C. associated disease prime targets vaccine development. We describe a plasmid-based system the production genetically modified in non-sporulating strain that lacks toxin genes tcdA tcdB. TcdA TcdB mutations targeting established glucosyltransferase cytotoxicity determinants were introduced into recombinant plasmids episomally expressed mutants purified from transformants. lacking autoproteolytic processing...
Candid1, a live-attenuated Junin virus vaccine strain, was developed during the early 1980s to control Argentine hemorrhagic fever, severe and frequently fatal human disease. Six amino acid substitutions were found be unique this their role in virulence attenuation mice analyzed using series of recombinant viruses. Our results indicate that Candid1 is attenuated through single substitution transmembrane domain G2 glycoprotein. This work provides insight into molecular mechanisms only...
ABSTRACT Ebola virus (EBOV) infection is a major public health concern due to high fatality rates and limited effective treatments. Statins, widely used cholesterol-lowering drugs, have pleiotropic mechanisms of action were suggested as potential adjunct therapy for disease (EVD) during the 2013–2016 outbreak in West Africa. Here, we evaluated antiviral effects statin (lovastatin) on EBOV vitro . Statin treatment decreased infectious production primary human monocyte-derived macrophages...
Significance Remdesivir is a nucleotide analog prodrug that has been evaluated in humans against acute Ebola virus disease; it also recently received emergency use authorization for treating COVID-19. For antiviral product development, the Food and Drug Administration recommends characterization of vitro selected resistant viruses to define specific mechanism action. This study identified single amino acid residue polymerase conferred low-level resistance remdesivir. The significance our...
Abstract There are no approved therapies for Ebola virus infection. Here, to find potential therapeutic targets, we perform a screen genes essential (EBOV) We identify GNPTAB , which encodes the α and β subunits of N-acetylglucosamine-1-phosphate transferase. show that EBOV infection knockout cell line is impaired, this reversed by reconstituting expression. Fibroblasts from patients with mucolipidosis II, disorder associated mutations in refractory EBOV, whereas cells their healthy parents...
The E2 protein of hepatitis C virus (HCV) is believed to be a virion surface glycoprotein that candidate for inclusion in an antiviral vaccine. A truncated soluble version has recently been shown interact with CD81, suggesting this may component the receptor HCV. When expressed eukaryotic cells, significant proportion forms misfolded aggregates. To analyze specificity interaction between and aggregated monomeric (E2(661)) were separated by high-pressure liquid chromatography analyzed CD81...
The recent development of infectious retroviral pseudotypes bearing hepatitis C virus (HCV) glycoproteins represents an opportunity to study the functionally active form HCV E1 and E2 glycoproteins. In culture supernatant cells producing pseudotypes, majority was not associated with particles failed sediment on sucrose gradients. that incorporated into appeared as a triplet diffuse bands at 60, 70, 90 kDa. Similarly, three major forms were pseudotype particles, migrating 33, 31, 25...
Host cell kinases are important for the replication of a number hemorrhagic fever viruses. We tested panel kinase inhibitors their ability to block multiple OSU-03012 inhibited Lassa, Ebola, Marburg and Nipah viruses, whereas BIBX 1382 dihydrochloride Ebola blocked both Lassa virus glycoprotein-dependent entry. These compounds may be used as tools understand conserved virus-host interactions, implicate host that targets broad spectrum therapeutic intervention.
ABSTRACT Lassa virus (LASV) infection is a major public health concern due to high fatality rates and limited effective treatment. The interferon-stimulated gene cholesterol 25-hydroxylase ( CH25H ) encodes an enzyme that catalyzes the production of 25-hydroxycholesterol (25HC). 25HC involved in regulating biosynthesis has recently been identified as potent antiviral targeting enveloped entry. Here, we show previously unrecognized role inhibiting LASV glycoprotein glycosylation infectious...
To determine whether 2 readily available indicators predicted survival among patients with Ebola virus disease in Sierra Leone, we evaluated information for 216 of the 227 Bo District during a 4-month period. The were time from symptom onset to healthcare facility admission and quantitative real-time reverse transcription PCR cycle threshold (Ct), surrogate viral load, first virus-positive blood sample tested. Of these patients, 151 alive when detected had reported dates Ct values available....