A5102993540- Virology and Viral Diseases
- Respiratory viral infections research
- interferon and immune responses
- Virus-based gene therapy research
- Viral Infections and Vectors
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Immunodeficiency and Autoimmune Disorders
- Polyomavirus and related diseases
- Cytokine Signaling Pathways and Interactions
- Protein purification and stability
- Bacteriophages and microbial interactions
- Herpesvirus Infections and Treatments
- Animal Virus Infections Studies
- Viral Infections and Immunology Research
- T-cell and B-cell Immunology
- Plant Virus Research Studies
- Cytomegalovirus and herpesvirus research
- Immunotherapy and Immune Responses
- Viral gastroenteritis research and epidemiology
- Parvovirus B19 Infection Studies
- Toxin Mechanisms and Immunotoxins
- IL-33, ST2, and ILC Pathways
- Spaceflight effects on biology
- Advanced biosensing and bioanalysis techniques
University of St Andrews
2010-2025
St George's, University of London
2004
University of London
2004
University of Victoria
1997
Most paramyxoviruses circumvent the IFN response by blocking signaling and limiting production of virus-infected cells. Here we report that highly conserved cysteine-rich C-terminal domain V proteins a wide variety binds melanoma differentiation-associated gene 5 (mda-5) product. mda-5 is an IFN-inducible host cell DExD/H box helicase contains caspase recruitment at its N terminus. Overexpression stimulated basal activity IFN- β promoter in reporter assays significantly enhanced activation...
To replicate in vivo, viruses must circumvent cellular antiviral defense mechanisms, including those induced by the interferons (IFNs). Here we demonstrate that simian virus 5 (SV5) blocks IFN signalling human cells inhibiting formation of IFN-stimulated gene factor 3 and gamma-activated transcription complexes are involved activating IFN-alpha/beta- IFN-gamma-responsive genes, respectively. SV5 inhibits these specifically targeting STAT1, a component common to both complexes, for...
Severe infectious disease in children may be a manifestation of primary immunodeficiency. These genetic disorders represent important experiments nature with the capacity to elucidate nonredundant mechanisms human immunity. We hypothesized that defect innate antiviral immunity was responsible for unusually severe viral illness two siblings; proband developed disseminated vaccine strain measles following routine immunization, whereas an infant brother died after 2-d febrile from unknown...
Human IFNAR2 deficiency causes fatal susceptibility to live viral vaccines.
Two canine isolates of simian virus 5 (SV5), termed CPI+ and CPI-, were examined for their ability to react with a bank monoclonal antibodies (MAbs) that had been previously raised against human isolate SV5. CPI-virus was originally isolated from the brain gnotobiotic dog infected establishes persistent infections more readily than in vitro. Of 50 MAbs tested, only one (P-k) reacted but not enabling distinction between two isolates. It shown MAb P-k reacts an epitope common both P V...
Summary Hybridomas secreting monoclonal antibodies to simian virus 5 (SV5) were obtained following immunization of mice with purified preparations a human isolate (LN) SV5. Immune precipitation studies showed that these had specificities for the haemagglutinin-neuraminidase (HN), fusion (F), nucleo-, matrix and phospho- (P) proteins By use radioimmune competition assay HN protein assigned four groups, members which recognized different antigenic sites on protein. All anti-HN anti-F antibody...
STAT2 R148W impairs an essential regulatory function of STAT2, revealing the damage wreaked by excessive IFNα/β activity.
ABSTRACT Human cell lines were isolated that express the V protein of either simian virus 5 (SV5) or human parainfluenza type 2 (hPIV2); termed 2f/SV5-V and 2f/PIV2-V, respectively. STAT1 was not detectable in cells, cells failed to signal response alpha/beta interferons (IFN-α IFN-β, IFN-α/β) gamma interferon (IFN-γ). In contrast, STAT2 absent from 2f/PIV2-V IFN-α/β but IFN-γ signaling blocked these cells. Treatment both with a proteasome inhibitor allowed respective STAT levels accumulate...
ABSTRACT Sendai virus (SeV) is highly pathogenic for mice. In contrast, mice (including SCID mice) infected with simian 5 (SV5) showed no overt signs of disease. Evidence presented that a major factor which prevented SV5 from productively infecting was its inability to circumvent the interferon (IFN) response in Thus, murine cells produce and respond IFN, protein synthesis rapidly switched off. marked once SeV began, it continued, even if culture medium supplemented alpha/beta IFN (IFN-α/β)....
ABSTRACT The V protein of simian virus 5 (SV5) blocks interferon signaling by targeting STAT1 for proteasome-mediated degradation. Here we present three main pieces evidence which demonstrate that the p127 subunit (DDB1) UV damage-specific DNA binding (DDB) plays a central role in this degradation process. First, an SV5 mutant fails to target does not bind DDB1. Second, mutations N and C termini abolish DDB1 also prevent from blocking (IFN) signaling. Third, treatment HeLa/SV5-V cells,...
The infection of cells by RNA viruses is associated with the recognition virus PAMPs (pathogen-associated molecular patterns) and production type I interferon (IFN). To counter this, most, if not all, encode antagonists IFN system. Here we present data on dynamics response during developing infections paramyxoviruses, influenza A bunyamwera virus. We show that only a limited number infected are responsible for IFN, this heterocellular feature infecting as opposed to an intrinsic property cells.
ABSTRACT Previous work has demonstrated that the V protein of simian virus 5 (SV5) targets STAT1 for proteasome-mediated degradation (thereby blocking interferon [IFN] signaling) in human but not murine cells. In BF cells, SV5 establishes a low-grade persistent infection which fluxes between active and repressed states response to local production IFN. Upon passage persistently infected mutants were selected better able replicate cells than parental W3 strain (wild type [wt]). Viruses with...
ABSTRACT The V protein of the paramyxovirus simian virus 5 blocks interferon (IFN) signaling by targeting STAT1 for proteasome-mediated degradation. Here we report on isolation human cell lines that express and can no longer respond to IFN. A variety viruses, particularly slow-growing wild-type viruses vaccine candidate (which are attenuated due mutations affect replication, spread, or ability circumvent IFN response), form bigger plaques grow titers increased as much 10- 4,000-fold in these...
Sequence comparison of the V/P and F genes 13 human, canine, porcine simian isolates virus 5 (SV5) revealed a surprising lack sequence variation at both nucleotide amino acid levels (0-3%), even though viruses were isolated over 30 years originated from countries around world. Furthermore, there no clear distinguishing or differences among that correlated completely with species which they isolated. In addition, was evidence ability to block interferon signalling by targeting STAT1 for...
ABSTRACT Preparations of parainfluenza virus 5 (PIV5) that are potent activators the interferon (IFN) induction cascade were generated by high-multiplicity passage in order to accumulate defective interfering genomes (DIs). Nucleocapsid RNA from these preparations was extracted and subjected deep sequencing. Sequencing data analyzed using methods designed detect internal deletion “copyback” DIs identify characterize different present approximately quantify ratio nondefective genomes. Trailer...
Paramyxoviruses can establish persistent infections both in vitro and vivo , some of which lead to chronic disease. However, little is known about the molecular events that contribute establishment by RNA viruses. Using parainfluenza virus type 5 (PIV5) as a model we show phosphorylation P protein, key component viral polymerase complex, determines whether or not transcription replication becomes repressed at late times after infection. If repressed, persistence established, but if not,...
We have previously shown that IFIT1 is primarily responsible for the antiviral action of interferon (IFN) alpha/beta against parainfluenza virus type 5 (PIV5), selectively inhibiting translation PIV5 mRNAs. Here we report while PIV2, PIV5, and mumps (MuV) are sensitive to IFIT1, nonrubulavirus members paramyxoviridae such as PIV3, Sendai (SeV), canine distemper (CDV) resistant. The sensitivity was not rescued by coinfection with an IFIT1-resistant (PIV3), demonstrating PIV3 does specifically...
Parainfluenza virus type 5 (PIV5) can cause either persistent or acute/lytic infections in a wide range of mammalian tissue culture cells. Here, we have generated PIV5 fusion (F)-expressing helper cell lines that support the replication F-deleted viruses. As proof principle single-cycle infectious viruses be used as safe and efficient expression vectors, cloned expressed humanized (Hu) version mouse anti-V5 tag antibody (clone SV5-Pk1). We show multiple different infected express high levels...
Parainfluenza virus 5 (PIV5) is a paramyxovirus that has been isolated from numerous mammalian hosts and notable for its ability to cause persistent infections. Although PIV5-infected cells are resistant IFN due the of V protein target STAT1 degradation, PIV5 shows residual sensitivity when infecting have already exposed IFN. We previously reported human IFN-stimulated gene with greatest inhibitory effect on IFIT1. IFIT1 inhibits translation incompletely methylated mRNAs (Cap0) but not those...
The P, V, and NP genes of the paramyxovirus simian virus 5 (SV5) were cloned such that their expression was regulated by tetracycline-controlled transactivator (M. Gossen H. Bujard, Proc. Natl. Acad. Sci. USA 89:5547-5551, 1992), mammalian cell lines inducibly expressed individually or protein coexpressed P plus V proteins isolated. A plasmid expresses linked, via foot-and-mouth disease 2A cleavage peptide sequence, to neomycin aminoglycoside phosphotransferase gene constructed. Cells...
Previous work has documented that the V protein of simian virus 5 (SV5) targets STAT1 for proteasome-mediated degradation, whilst human parainfluenza type 2 (hPIV2) STAT2. Here, it was shown processes ubiquitination and degradation could be reconstructed in vitro by using programmed rabbit reticulocyte lysates. Using this system, addition bacterially expressed purified SV5 to lysates demonstrated result polyubiquitination -translated STAT1, but only if STAT2 also present. Surprisingly, same...
Efficient herpes simplex virus type 1 (HSV-1) infection of human fibroblasts (HFs) is highly dependent on the viral immediate-early regulatory protein ICP0 unless conducted at a high multiplicity. ICP0-null mutant HSV-1 exhibits plaque-forming defect up to 3 orders magnitude in HFs, whereas many other cell types, this varies between 10- and 30-fold. The reasons for requirement HFs have not been established definitively. Previous studies using types suggested that hypersensitive interferon...