Abstract:
:Dengue virus (DENV) infection causes serious clinical symptoms, including dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Vascular permeability change is the main feature of the diseases, and the abnormal expression of proinflammatory cytokines is the important cause of vascular permeability change. However, the mechanism underlying vascular permeability induced by DENV has not been fully elucidated. Here, we reveal a distinct mechanism by which DENV infection promotes NLRP3 inflammasome activation and interleukin-1 beta (IL-1β) release to induce endothelial permeability and vascular leakage in mice. DENV M protein interacts with NLRP3 to facilitate NLRP3 inflammasome assembly and activation, which induce proinflammatory cytokine IL-1β activation and release. Notably, M can induce vascular leakage in mouse tissues by activating the NLRP3 inflammasome and IL-1β. More importantly, inflammatory cell infiltration and tissue injuries are induced by M in wild-type (WT) mouse tissues, but they are not affected by M in NLRP3 knockout (NLRP3-/-) mouse tissues. Evans blue intensities in WT mouse tissues are significantly higher than in NLRP3-/- mouse tissues, demonstrating an essential role of NLRP3 in M-induced vascular leakages in mice. Therefore, we propose that upon DENV infection, M interacts with NLRP3 to facilitate inflammasome activation and IL-1β secretion, which lead to the induction of endothelial permeability and vascular leakage in mouse tissues. The important role of the DENV-M-NLRP3-IL-1β axis in the induction of vascular leakage provides new insights into the mechanisms underlying DENV pathogenesis and DENV-associated DHF and DSS development.IMPORTANCE Dengue virus (DENV) is a mosquito-borne pathogen, and infections by this virus are prevalent in over 100 tropical and subtropical countries or regions, with approximately 2.5 billion people at risk. DENV infection induces a spectrum of clinical symptoms, ranging from classical dengue fever (DF) to severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Therefore, it is important to understand the mechanisms underlying DENV pathogenesis. In this study, we reveal that the DENV membrane protein (M) interacts with the host NLRP3 protein to promote NLRP3 inflammasome activation, which leads to the activation and release of a proinflammatory cytokine, interleukin-1 beta (IL-1β). More importantly, we demonstrate that M protein can induce vascular permeability and vascular leakage and that NLRP3 is required for M-induced vascular leakage in mouse tissues. Collectively, this study reveals a distinct mechanism underlying DENV pathogeneses and provides new insights into the development of therapeutic agents for DENV-associated diseases.
journal_name
J Viroljournal_title
Journal of virologyauthors
Pan P,Zhang Q,Liu W,Wang W,Lao Z,Zhang W,Shen M,Wan P,Xiao F,Liu F,Zhang W,Tan Q,Liu X,Wu K,Liu Y,Li G,Wu Jdoi
10.1128/JVI.00996-19subject
Has Abstractpub_date
2019-10-15 00:00:00issue
21eissn
0022-538Xissn
1098-5514pii
JVI.00996-19journal_volume
93pub_type
杂志文章abstract:UNLABELLED:Influenza virus hemagglutinin (HA) mediates virus entry by binding to cell surface receptors and fusing the viral and endosomal membranes following uptake by endocytosis. The acidic environment of endosomes triggers a large-scale conformational change in the transmembrane subunit of HA (HA2) involving a loop...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00939-15
更新日期:2015-10-01 00:00:00
abstract::Epstein-Barr virus (EBV) is a lymphotrophic herpesvirus infecting most of the world's population. It is associated with a number of human lymphoid and epithelial tumors and lymphoproliferative diseases in immunocompromised patients. Recent studies have shown an in vitro and in vivo interaction between the EBV nuclear ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.17.8702-8709.2002
更新日期:2002-09-01 00:00:00
abstract::The proteins of purified avian oncoviruses were analyzed by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and isoelectric focusing. Certain members of the avian leukosis-sarcoma viruses (ALSV) had group-specific antigens with altered electrophoretic properties. (i) The p27 protein of Rous-associated ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.24.3.850-864.1977
更新日期:1977-12-01 00:00:00
abstract::Two murine leukemia viruses were isolated from JLS-V9 cells which had been infected with Rauscher plasma virus. One virus was XC positive and failed to grow on mink or cat cells and thus was an ecotropic virus. The other virus formed cytopathic foci on mink cells, was XC negative, and fell into the mink cell focus-for...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.45.3.995-1003.1983
更新日期:1983-03-01 00:00:00
abstract::The Parvovirus H-1 replicates autonomously in hamster embryo cells. A DNA synthetic event, called HA-DNA synthesis, upon which subsequent viral RNA and viral hemagglutinin synthesis is dependent, is initiated in late S phase of the infected cell (18). It was postulated that HA-DNA represents parental viral replicative...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.13.2.400-410.1974
更新日期:1974-02-01 00:00:00
abstract::The number, chromosomal distribution, and insertional polymorphisms of endogenous feline leukemia viruses (enFeLVs) were determined in four domestic cats (Burmese, Egyptian Mau, Persian, and nonbreed) using fluorescent in situ hybridization and radiation hybrid mapping. Twenty-nine distinct enFeLV loci were detected a...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.7.3979-3986.2005
更新日期:2005-04-01 00:00:00
abstract::In Epstein-Barr virus (EBV)-carrying nonproducer Raji cells, the induction of the viral replicative cycle by chemical treatment is limited to only the early stage and viral DNA synthesis is totally inhibited. We previously showed the absence of two messenger RNAs that are encoded by the BamHI-A fragment of the EBV gen...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.11.7309-7314.1995
更新日期:1995-11-01 00:00:00
abstract::Our previous studies showed that establishment of murine cytomegalovirus (MCMV) latency in vivo is associated with repression of immediate-early gene expression, deacetylation of histones bound to the major immediate-early promoter (MIEP), changes in patterns of methylation of histones, and recruitment of cellular rep...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02380-09
更新日期:2010-04-01 00:00:00
abstract::Although the major component of the prion is believed to be the oligomer of PrP(Sc), little information is available concerning regions on the PrP(Sc) molecule that affect prion infectivity. During the analysis of PrP(Sc) molecules from various prion strains, we found that PrP(Sc) of the Chandler strain showed a uniqu...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01740-08
更新日期:2009-04-01 00:00:00
abstract::Arginine methylation of human immunodeficiency virus type 1 (HIV-1) Tat protein downregulates its key function in viral-gene transactivation. The fate of methylated Tat is unknown, so it is unclear whether methylated Tat is degraded or persists in the cell for additional functions. Here we show that the arginine methy...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00499-09
更新日期:2009-11-01 00:00:00
abstract::Different tombusviruses were able to support the replication of either homologous or heterologous defective interfering (DI) RNAs, and those infected plants usually developed typical attenuated symptoms. However, in some helper virus-DI RNA combinations the inoculated plants were necrotized, although they contained a ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.7.6251-6256.1998
更新日期:1998-07-01 00:00:00
abstract::Using a yeast two-hybrid screen of a T-cell cDNA library to identify cellular proteins that bind to the human immunodeficiency virus type 2 (HIV-2) Gag polyprotein, we identified PRP4, a serine-threonine protein kinase. Specific interaction of PRP4 and HIV-2 Gag was confirmed in in vitro and in vivo assays. The intera...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.20.11303-11312.2004
更新日期:2004-10-01 00:00:00
abstract::Two hundred forty pyridazinamine derivatives were tested for the ability to stabilize the antigenicity and infectivity of oral poliovirus vaccine subjected to 45 degrees C for 2 h. Seven compounds stabilized the antigenicity of all three vaccine strains and neutralized the viral particles in a way that is reversible b...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.5.3397-3400.1994
更新日期:1994-05-01 00:00:00
abstract::The NS3 protein of hepatitis C virus (HCV) possesses protease activity responsible for the proteolytic cleavage of the viral polyprotein at the junctions of nonstructural proteins downstream of NS3. The NS3 protein was also found to be internally cleaved. In this study, we demonstrated that internal cleavages occurred...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00348-07
更新日期:2007-08-01 00:00:00
abstract::Epstein-Barr Virus (EBV) generates a variety of viral microRNAs (miRNAs) by processing the BHRF1 and BamHI A rightward (BART) transcripts. BART miRNAs are expressed in all cells latently infected with EBV, but the functions of most BART miRNAs remain unknown. The results of a cell proliferation assay revealed that miR...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03159-12
更新日期:2013-07-01 00:00:00
abstract::Previously it was shown that the host-range gene of the Bratislava strain of avain sarcoma virus (B77 virus) spontaneously mutates with a very high rate. The wild-type B77 virus called B77 virus-II, mutates either to virus that efficiently infects duck cells (B77 virus-III) or to virus that does not mutate to the abil...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.21.1.105-112.1977
更新日期:1977-01-01 00:00:00
abstract::Hepatitis E virus (HEV) is a common cause of acute viral hepatitis worldwide. Most HEV infections are asymptomatic, but immunocompromised patients infected with HEV genotype 3 (HEV3), HEV4, or HEV7 may develop chronic infections. The HEV particles in stools are naked (nHEV), while those in the serum and culture supern...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01207-18
更新日期:2019-02-05 00:00:00
abstract::The nucleotide sequence of the region of human polyoma virus JC DNA between 0.5 and 0.7 map units from a unique EcoRI cleavage site was determined and compared with those of the corresponding regions of another human polyoma virus, BK, and simian virus 40 DNAs. Within this region consisting of 945 base pairs, we locat...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.45.1.73-79.1983
更新日期:1983-01-01 00:00:00
abstract::We have identified a cytomegalovirus virion protein capable of modulating the rapid induction of an interferon-like response in cells that follows virus binding and penetration. Functional genomics revealed a role for the major cytomegalovirus structural protein, pp65 (ppUL83), in counteracting this response. The unde...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.20.10995-11006.2004
更新日期:2004-10-01 00:00:00
abstract::We previously showed that the cellular proteins ZEB1 and ZEB2/SIP1 both play key roles in regulating the latent-lytic switch of Epstein-Barr Virus (EBV) by repressing BZLF1 gene expression. We investigated here the effects of cellular microRNA (miRNA) 200 (miR200) family members on the EBV infection status of cells. W...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00923-10
更新日期:2010-10-01 00:00:00
abstract::For the identification of RNA-binding proteins that specifically interact with potato spindle tuber viroid (PSTVd), we subjected a tomato cDNA expression library prepared from viroid-infected leaves to an RNA ligand screening procedure. We repeatedly identified cDNA clones that expressed a protein of 602 amino acids. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.17.9685-9694.2003
更新日期:2003-09-01 00:00:00
abstract::Phosphorylation of viral proteins plays important roles in the influenza A virus (IAV) life cycle. By using mass spectrometry, we identified tyrosine 132 (Y132) as a phosphorylation site of the matrix protein (M1) of the influenza virus A/WSN/1933(H1N1). Phosphorylation at this site is essential to the process of viru...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03024-12
更新日期:2013-06-01 00:00:00
abstract::The effect of NS1 protein on the efficiency of influenza virus mRNA translation was evaluated by determining the accumulation of nucleoprotein (NP) or M1 mRNAs in the cytoplasm of cells expressing either of these genes alone or in combination with the NS1 gene, as well as the total cell accumulation of NP or M1 protei...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.4.2427-2433.1995
更新日期:1995-04-01 00:00:00
abstract::The present study used the cottontail rabbit papillomavirus DNA-rabbit system to evaluate whether the regulatory genes E1 and E2 and the transforming gene E6 are required for papilloma formation. Frameshift mutations were generated in the individual genes in the context of a full-length cottontail rabbit papillomaviru...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.9.6097-6102.1994
更新日期:1994-09-01 00:00:00
abstract::While RNA silencing is a potent antiviral defense in plants, well-adapted plant viruses are known to encode suppressors of RNA silencing (VSR) that can neutralize the effectiveness of RNA silencing. As a result, most plant genes involved in antiviral silencing were identified by using debilitated viruses lacking silen...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00497-12
更新日期:2012-06-01 00:00:00
abstract::The uncoating of adenovirus type 2 and a temperature-sensitive mutant, tsl, was studied. HEp-2 cells were infected with 32P- OR 125I-labeled purified virions for various lengths of time, and the nuclear and cytoplasmic fractions were analyzed by sucrose gradient velocity sedimentation and sodium dodecyl sulfate-polyac...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.30.2.462-471.1979
更新日期:1979-05-01 00:00:00
abstract::Relatively little is known at the functional genomic level about the global host response to human immunodeficiency virus type 1 (HIV-1) infection. Microarray analyses by several laboratories, including our own, have revealed that HIV-1 infection causes significant changes in host mRNA abundance and regulation of seve...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00288-07
更新日期:2007-07-01 00:00:00
abstract::The C-terminal half of the replicase ORF1a polyprotein of the arterivirus equine arteritis virus is processed by a chymotrypsinlike serine protease (SP) (E. J. Snijder et al., J. Biol. Chem. 271:4864-4871, 1996) located in nonstructural protein 4 (nsp4). Three probable SP cleavage sites had previously been identified ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.12.9313-9322.1997
更新日期:1997-12-01 00:00:00
abstract::Human papillomavirus type 1 (HPV1) E4 protein is associated with cytoplasmic and nuclear inclusions in productively infected keratinocytes. Here we have used transient expression of HPV1 E4 (also known as E1E4) protein in keratinocytes to reproduce formation of E4 inclusions. Immunofluorescence analysis showed that pr...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.1.673-684.2003
更新日期:2003-01-01 00:00:00
abstract::Published work (D. J. McGeoch, Nucleic Acids Res. 18:4105-4110, 1990; J. E. McGeehan, N. W. Depledge, and D. J. McGeoch, Curr. Protein Peptide Sci. 2:325-333, 2001) has indicated that evolution of dUTPase in the class of herpesviruses that infect mammals and birds involved capture of a host gene followed by a duplicat...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.20.12880-12892.2005
更新日期:2005-10-01 00:00:00