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NS4/5 mutations enhance flavivirus Bamaga virus infectivity and pathogenicity in vitro and in vivo.Flaviviruses such as yellow fever, dengue or Zika viruses are responsible for significant human and veterinary diseases worldwide. These viruses contain an RNA genome, prone to mutations, which enhances their potential to emerge as pathogens. Bamaga virus (BgV) is a mosquito-borne flavivirus in the yellow fever virus group that we have previously shown to be host-restricted in vertebrates and horizontally transmissible by Culex mosquitoes. Here, we aimed to characterise BgV host-restriction and to investigate the mechanisms involved. We showed that BgV could not replicate in a wide range of vertebrate cell lines and animal species. We determined that the mechanisms involved in BgV host-restriction were independent of the type-1 interferon response and RNAse L activity. Using a BgV infectious clone and two chimeric viruses generated as hybrids between BgV and West Nile virus, we demonstrated that BgV host-restriction occurred post-cell entry. Notably, BgV host-restriction was shown to be temperature-dependent, as BgV replicated in all vertebrate cell lines at 34°C but only in a subset at 37°C. Serial passaging of BgV in Vero cells resulted in adaptive mutants capable of efficient replication at 37°C. The identified mutations resulted in amino acid substitutions in NS4A-S124F, NS4B-N244K and NS5-G2C, all occurring close to a viral protease cleavage site (NS4A/2K and NS4B/NS5). These mutations were reverse engineered into infectious clones of BgV, which revealed that NS4B-N244K and NS5-G2C were sufficient to restore BgV replication in vertebrate cells at 37°C, while NS4A-S124F further increased replication efficiency. When these mutant viruses were injected into immunocompetent mice, alongside BgV and West Nile virus chimeras, infection and neurovirulence were enhanced as determined by clinical scores, seroconversion, micro-neutralisation, viremia, histopathology and immunohistochemistry, confirming the involvement of these residues in the attenuation of BgV. Our studies identify a new mechanism of host-restriction and attenuation of a mosquito-borne flavivirus.
1221 related Products with: NS4/5 mutations enhance flavivirus Bamaga virus infectivity and pathogenicity in vitro and in vivo.Adeno Associated Virus (A Adeno Associated Virus (A 2-Bromo-1-indanol CAS: [5 C Peptide ELISA Kit, Rat MarkerGeneTM in vivo lacZ Native Influenza A Virus Integrin β1 (CD29) Antib SAHA (Vorinostat) Mechani Inhibitory Mouse Monoclon Mouse Anti-Influenza A Vi Native Parainfluenza Viru Rabbit Plasma US Origin I
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Zika virus non-structural protein NS4A restricts eye growth in through regulation of JAK/STAT signaling.To gain a comprehensive view of the changes in host gene expression underlying Zika virus (ZIKV) pathogenesis, we performed whole-genome mRNAseq of ZIKV infected adult flies. RNA-seq analysis revealed that ZIKV infection alters several and diverse biological processes including stress, locomotion, lipid metabolism, imaginal disc morphogenesis and regulation of JAK/STAT signaling, To explore the interaction between ZIKV infection and JAK/STAT signaling regulation, we generated genetic constructs overexpressing ZIKV-specific non-structural proteins NS2A, NS2B, NS4A and NS4B. We find that ectopic expression of non-structural proteins in the developing eye significantly restricts growth of the larval and adult eye and correlates with a considerable repression of the JAK/STAT reporter, At the cellular level, eye growth defects are associated with reduced rate of proliferation without affecting the overall rate of apoptosis. In addition, ZIKV NS4A genetically interacts with the JAK/STAT signaling components; co-expression of along with dominant negative form of results in aggravated reduction in eye size while co-expression of in mutant background partially rescues the -induced eye overgrowth phenotype. The function of ZIKV NS4A in regulating growth is maintained in the wing, where ZIKV overexpression in the pouch domain results in reduced growth linked with diminished expression of Notch targets, Wingless and Cut and the Notch reporter Thus, our study provides evidence that ZIKV infection in results in restricted growth of the developing eye and wing, wherein eye phenotype is induced through regulation of JAK/STAT signaling while restricted wing growth is through regulation of Notch signaling. The interaction of ZIKV non-structural proteins with the conserved host signaling pathways further advance our understanding of ZIKV-induced pathogenesis.
1499 related Products with: Zika virus non-structural protein NS4A restricts eye growth in through regulation of JAK/STAT signaling.STAT5B & GHR Protein Prot RET & STAT3 Protein Prote Goat Anti-Influenza A Vir EGFR & STAT3 Protein Prot Rat monoclonal anti mouse Anti-Infectious Pancreati STAT5B & CTLA4 Protein Pr STAT1 & PDGFRA Protein Pr IGF1R & STAT3 Protein Pro IGF-1R Signaling Phospho- STAT1 & PIAS1 Protein Pro Mouse Anti-Influenza A Vi
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Selective Reactivity of Anti-Japanese Encephalitis Virus NS4B Antibody Towards Different Flaviviruses.Studies investigating West Nile virus (WNV) NS4B protein function are hindered by the lack of an antibody recognizing WNV NS4B protein. Few laboratories have produced WNV NS4B antibodies, and none have been shown to work consistently. In this report, we describe a NS4B antibody against Japanese encephalitis virus (JEV) NS4B protein that cross-reacts with the NS4B protein of WNV but not of dengue virus (DENV). This JEV NS4B antibody not only recognizes WNV NS4B in infected cells, but also recognizes the NS4B protein expressed using transfection. It is evident from this data that the JEV NS4B antibody is specific to NS4B of WNV but not to NS4B of the four DENV serotypes. The specificity of this antibody may be due to the notable differences that exist between the amino acid sequence identity and antigenic relationships within the NS4B protein of the WNV, DENV, and JEV.
2418 related Products with: Selective Reactivity of Anti-Japanese Encephalitis Virus NS4B Antibody Towards Different Flaviviruses.Rabbit Anti-Hepatitis C V Rabbit Anti-Hepatitis C V Rabbit Anti-Hepatitis C V Rabbit Anti-Hepatitis C V Rabbit Anti-IEX1 Differen Rabbit Anti-Hepatitis C V Rabbit Anti-Hepatitis C V Rabbit Anti-Hepatitis C V Rabbit Anti-Hepatitis C V Rabbit Anti-Hepatitis C V Rabbit Anti-Hepatitis C V Rabbit Anti-IEX1 Differen
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Whole genome sequencing and genetic variations in several dengue virus type 1 strains from unusual dengue epidemic of 2017 in Vietnam.Dengue hemorrhagic fever is an acute viral infection transmitted by mosquitoes. In the 2017, a dengue epidemic occurred in Hanoi in a short time interval and many cases were serious with associated mortality. This was the largest and unusual dengue fever outbreak in the North of Vietnam over the past 20 years. The objective of the present study was to understand the genetic characteristics of the DENV-1 strain in the 2017 epidemic and its relationship with previous viruses in Vietnam and the rest of the world.
1072 related Products with: Whole genome sequencing and genetic variations in several dengue virus type 1 strains from unusual dengue epidemic of 2017 in Vietnam.Recombinant Dengue Virus Recombinant Dengue Virus Native Parainfluenza Viru Dengue Type 2 Recombinant Dengue Virus Recombinant Dengue Virus Native Parainfluenza Viru Recombinant Influenza (H5 Dengue Type 4 Antibody Recombinant Dengue Virus Recombinant Dengue Virus Recombinant Dengue Virus
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Proton-Detected Solid-State NMR of the Cell-Free Synthesized α-Helical Transmembrane Protein NS4B from Hepatitis C Virus.Proton-detected 100 kHz magic-angle-spinning (MAS) solid-state NMR is an emerging analysis method for proteins with only hundreds of microgram quantities, and thus allows structural investigation of eukaryotic membrane proteins. This is the case for the cell-free synthesized hepatitis C virus (HCV) nonstructural membrane protein 4B (NS4B). We demonstrate NS4B sample optimization using fast reconstitution schemes that enable lipid-environment screening directly by NMR. 2D spectra and relaxation properties guide the choice of the best sample preparation to record 2D H-detected H, N and 3D H, C, N correlation experiments with linewidths and sensitivity suitable to initiate sequential assignments. Amino-acid-selectively labeled NS4B can be readily obtained using cell-free synthesis, opening the door to combinatorial labeling approaches which should enable structural studies.
1690 related Products with: Proton-Detected Solid-State NMR of the Cell-Free Synthesized α-Helical Transmembrane Protein NS4B from Hepatitis C Virus.Rabbit Anti-Hepatitis C V Rabbit Anti-Hepatitis C V Rabbit Anti-Hepatitis C V Rabbit Anti-Hepatitis C V Rabbit Anti-Hepatitis C V Rabbit Anti-Hepatitis C V Rabbit Anti-Hepatitis C V Rabbit Anti-Hepatitis C V Rabbit Anti-Hepatitis C V Rabbit Anti-Hepatitis C V Rabbit Anti-Hepatitis C V Rabbit Anti-Hepatitis C V
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