Abstract:
UNLABELLED:Barrier dysfunction of airway epithelium may increase the risk for acquiring secondary infections or allergen sensitization. Both rhinovirus (RV) and polyinosinic-polycytidilic acid [poly(I·C)], a double-stranded RNA (dsRNA) mimetic, cause airway epithelial barrier dysfunction, which is reactive oxygen species (ROS) dependent, implying that dsRNA generated during RV replication is sufficient for disrupting barrier function. We also demonstrated that RV or poly(I·C)-stimulated NADPH oxidase 1 (NOX-1) partially accounts for RV-induced ROS generation. In this study, we identified a dsRNA receptor(s) contributing to RV-induced maximal ROS generation and thus barrier disruption. We demonstrate that genetic silencing of the newly discovered dsRNA receptor Nod-like receptor X-1 (NLRX-1), but not other previously described dsRNA receptors, abrogated RV-induced ROS generation and reduction of transepithelial resistance (R(T)) in polarized airway epithelial cells. In addition, both RV and poly(I·C) stimulated mitochondrial ROS, the generation of which was dependent on NLRX-1. Treatment with Mito-Tempo, an antioxidant targeted to mitochondria, abolished RV-induced mitochondrial ROS generation, reduction in R(T), and bacterial transmigration. Furthermore, RV infection increased NLRX-1 localization to the mitochondria. Additionally, NLRX-1 interacts with RV RNA and poly(I·C) in polarized airway epithelial cells. Finally, we show that NLRX-1 is also required for RV-stimulated NOX-1 expression. These findings suggest a novel mechanism by which RV stimulates generation of ROS, which is required for disruption of airway epithelial barrier function. IMPORTANCE:Rhinovirus (RV), a virus responsible for a majority of common colds, disrupts the barrier function of the airway epithelium by increasing reactive oxygen species (ROS). Poly(I·C), a double-stranded RNA (dsRNA) mimetic, also causes ROS-dependent barrier disruption, implying that the dsRNA intermediate generated during RV replication is sufficient for this process. Here, we demonstrate that both RV RNA and poly(I·C) interact with NLRX-1 (a newly discovered dsRNA receptor) and stimulate mitochondrial ROS. We show for the first time that NLRX-1 is primarily expressed in the cytoplasm and at the apical surface rather than in the mitochondria and that NLRX-1 translocates to mitochondria following RV infection. Together, our results suggest a novel mechanism for RV-induced barrier disruption involving NLRX-1 and mitochondrial ROS. Although ROS is necessary for optimal viral clearance, if not neutralized efficiently, it may increase susceptibility to secondary infections and alter innate immune responses to subsequently inhaled pathogens, allergens, and other environmental factors.
journal_name
J Viroljournal_title
Journal of virologyauthors
Unger BL,Ganesan S,Comstock AT,Faris AN,Hershenson MB,Sajjan USdoi
10.1128/JVI.03039-13subject
Has Abstractpub_date
2014-04-01 00:00:00pages
3705-18issue
7eissn
0022-538Xissn
1098-5514pii
JVI.03039-13journal_volume
88pub_type
杂志文章abstract::Open reading frame P (ORF P), located at the 3' terminus of the 8.5-kb DNA sequence transcribed during latency and almost completely antisense to the gamma(1)34.5 gene, is naturally repressed by infected cell protein 4 (ICP4), the major herpes simplex virus 1 regulatory protein. Earlier studies on cells infected with ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.10.7750-7757.1997
更新日期:1997-10-01 00:00:00
abstract::Nucleotide sequencing and phylogenetic analysis of 10 recognized prototype strains of the porcine enterovirus (PEV) cytopathic effect (CPE) group I reveals a close relationship of the viral genomes to the previously sequenced strain F65, supporting the concept of a reclassification of this virus group into a new picor...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.4.1620-1631.2001
更新日期:2001-02-01 00:00:00
abstract::Pathogens such as HIV-1, with their minimalist genomes, must navigate cellular networks and rely on hijacking and manipulating the host machinery for successful replication. Limited overlap of host factors identified as vital for pathogen replication may be explained by considering that pathogens target, rather than s...
journal_title:Journal of virology
pub_type: 杂志文章,评审
doi:10.1128/JVI.03684-14
更新日期:2015-05-01 00:00:00
abstract::Analysis of purified simian rotavirus has shown that it contains fewer structural polypeptide classes than previously reported. Two polypeptides (molecular weights, 62,000 and 28,000) commonly found in purified rotaviruses were, in fact, produced by cleavage of a larger structural polypeptide (molecular weight, about ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.37.1.156-160.1981
更新日期:1981-01-01 00:00:00
abstract:UNLABELLED:The cytosolic RIG-I (retinoic acid-inducible gene I) receptor plays a pivotal role in the initiation of the immune response against RNA virus infection by recognizing short 5'-triphosphate (5'ppp)-containing viral RNA and activating the host antiviral innate response. In the present study, we generated novel...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00845-15
更新日期:2015-08-01 00:00:00
abstract::Molecular clones of closed circular DNA molecules of a mink cell focus-inducing murine leukemia virus (MCF-13 MuLV) were generated. Closed circular DNA molecules isolated from a Hirt extraction of recently infected NIH/3T3 cells were inserted at their unique EcoRI site into lambda gtWES.lambda B. Restriction endonucle...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.43.1.348-351.1982
更新日期:1982-07-01 00:00:00
abstract::Cell cycle progression during cytomegalovirus infection was investigated by fluorescence-activated cell sorter (FACS) analysis of the DNA content in growth-arrested as well as serum-stimulated human fibroblasts. Virus-infected cells maintained in either low (0.2%) or high (10%) serum failed to progress into S phase an...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.2.1629-1634.1997
更新日期:1997-02-01 00:00:00
abstract::The fraction of the adenovirus type 5 genome expressed as mRNA in a rat cell line, 5RK, transformed by the HsuI-G restriction fragment was analyzed by saturation hybridization using separated strands of 32P-labeled HindIII-G fragment. It was found that 45 to 50% of G fragment (about 8 X 10(5) daltons) is expressed as ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.28.3.1011-1014.1978
更新日期:1978-12-01 00:00:00
abstract::Bovine spongiform encephalopathy (BSE) is a fatal, transmissible, neurodegenerative disease of cattle. BSE can be transmitted experimentally between cattle through the oral route, and in this study, brain tissue samples from animals at different time points postinoculation were analyzed for changes in gene expression....
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00352-09
更新日期:2009-09-01 00:00:00
abstract:UNLABELLED:The majority of currently circulating influenza A(H1N1) viruses are antigenically similar to the virus that caused the 2009 influenza pandemic. However, antigenic variants are expected to emerge as population immunity increases. Amino acid substitutions in the hemagglutinin protein can result in escape from ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02962-14
更新日期:2015-04-01 00:00:00
abstract::Nonstructural protein 5A (NS5A) is a membrane-associated essential component of the hepatitis C virus (HCV) replication complex. An N-terminal amphipathic alpha helix mediates in-plane membrane association of HCV NS5A and at the same time is likely involved in specific protein-protein interactions required for the ass...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01279-06
更新日期:2007-03-01 00:00:00
abstract::In immunocompromised patients, infection with Kaposi's sarcoma-associated herpesvirus (KSHV) can give rise to Kaposi's sarcoma and several lymphoproliferative disorders. In these tumors, KSHV establishes a latent infection in many of the rapidly proliferating and morphologically abnormal cells. Only a few viral gene p...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.18.10074-10085.2004
更新日期:2004-09-01 00:00:00
abstract::Antibodies directed to Sindbis virus (SV) envelope protein E2 are able to control virus replication in vivo and in persistently infected cultures of neurons in vitro. We investigated the mechanisms by which anti-E2 monoclonal antibody (MAb) alters virus replication by using AT3 rat prostatic carcinoma cells expressing...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.11.7006-7014.1995
更新日期:1995-11-01 00:00:00
abstract::Storage of the dimeric (alphabeta) form of avian myeloblastosis virus (AMV) DNA polymerase in glycerol resulted in the release of the smaller alpha subunit, as detected by glycerol gradient sedimentation. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of enzyme stored in glycerol showed the conc...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.18.3.904-910.1976
更新日期:1976-06-01 00:00:00
abstract::We have selected neutralization escape mutants by using a monoclonal antibody (nt-MAb) against a sequential epitope between amino acids 93 through 104 (neutralization antigenic site I) of poliovirus type 1 Mahoney. The majority of mutants were also resistant against five strain-specific nt-MAbs which recognized confor...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.5.1845-1848.1988
更新日期:1988-05-01 00:00:00
abstract::Antiserum against murine cytomegalovirus produced in the rabbit contained complement (C')-requiring neutralizing (CRN) antibody. The proportion of CRN was extremely high (up to 98%) during the early portion of an immunization procedure, whereas the antisera produced late had a much lower proportion that required C'. T...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.12.6.1620-1621.1973
更新日期:1973-12-01 00:00:00
abstract::p60src, the transforming protein of Rous sarcoma virus, was found to contain 0.5 to 0.9 mol of total phosphate per mol of polypeptide. The protein is known to be phosphorylated at two sites, a serine in the amino-terminal domain and a tyrosine in the carboxy-terminal domain. Because our indirect analysis suggests that...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.41.3.813-820.1982
更新日期:1982-03-01 00:00:00
abstract::Respiratory syncytial virus (RSV) is a major cause of morbidity and mortality. Previous studies have suggested that T-cell responses may contribute to RSV immunopathology, which could be driven by dendritic cells (DCs). DCs are productively infected by RSV, and during RSV infections, there is an increase of DCs in the...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01273-10
更新日期:2010-12-01 00:00:00
abstract::The localization of H-1 viral replicative-form double-stranded DNA and progeny single-stranded DNA replication in parasynchronously infected, simian virus 40-transformed newborn human kidney cells was studied with high-resolution electron microscope autoradiography (80-nm silver grains). We analyzed wild-type H-1 and ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.25.1.349-360.1978
更新日期:1978-01-01 00:00:00
abstract::Friend murine spleen focus-forming virus (SFFV) encodes a glycoprotein designated gp52, which is responsible for the leukemogenic properties of the virus. gp52 lacks a cytoplasmic domain and is defective in its transport to the cell surface. We constructed a chimeric envelope gene which codes for a molecule with an ex...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.12.4007-4011.1987
更新日期:1987-12-01 00:00:00
abstract::Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA) is a 1,162-amino-acid protein that mediates episome persistence of viral genomes. LANA binds the KSHV terminal-repeat (TR) sequence through its carboxy-terminal domain to mediate DNA replication. LANA simultaneously binds mitotic ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02158-18
更新日期:2019-03-05 00:00:00
abstract::Measles virus (MeV) is an enveloped RNA virus bearing two envelope glycoproteins, the hemagglutinin (H) and fusion (F) proteins. Upon receptor binding, the H protein triggers conformational changes of the F protein, causing membrane fusion and subsequent virus entry. MeV may persist in the brain, infecting neurons and...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01727-19
更新日期:2020-01-06 00:00:00
abstract::A putative transcription factor, C/EBP, isolated from rat liver nuclei, has been shown to bind to at least two different sequence motifs: the CCAAT promoter domain and a core sequence [GTGG(T/A)(T/A)(T/A)G] common to many viral enhancers, including simian virus 40 and human hepatitis B virus. It has been proposed that...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.4.1517-1522.1990
更新日期:1990-04-01 00:00:00
abstract::Bluetongue virus (BTV), a member of the Reoviridae family, is an insect-borne animal pathogen. Virus release from infected cells is predominantly by cell lysis, but some BTV particles are also released from the plasma membrane. The nonstructural protein NS3 has been implicated in this process. Using alternate initiato...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02352-10
更新日期:2011-05-01 00:00:00
abstract::The intranuclear structure of parental adenovirus 2 DNA was studied using digestion with micrococcal nuclease as a probe. When cultures were infected with 32P-labeled virions, at a multiplicity of 3,000 particles per cell, 14 to 21% of parental DNA penetrated the cell and reached the nucleus. Of this parental DNA, 60%...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.29.3.888-898.1979
更新日期:1979-03-01 00:00:00
abstract::Although combination therapy allows the suppression of human immunodeficiency virus type 1 (HIV-1) viremia to undetectable levels, eradication has not been achieved because the virus persists in cellular reservoirs, particularly the latent reservoir in resting CD4(+) T lymphocytes. We previously established a simian i...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01396-06
更新日期:2007-02-01 00:00:00
abstract::In 2002, severe acute respiratory syndrome (SARS)-coronavirus (CoV) appeared as a novel human virus with high similarity to bat coronaviruses. However, while SARS-CoV uses the human angiotensin-converting enzyme 2 (ACE2) receptor for cellular entry, no coronavirus isolated from bats appears to use ACE2. Here we show t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00311-12
更新日期:2012-06-01 00:00:00
abstract::We have previously reported that infection of 9- to 13-day-old chicken embryos with RAV-1 results in rapid development of a novel B-cell lymphoma in which proviral insertion has activated expression of the c-myb gene (E. Pizer and E. H. Humphries, J. Virol. 63:1630-1640, 1989). The biological properties of these B-cel...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.1.512-523.1992
更新日期:1992-01-01 00:00:00
abstract:UNLABELLED:Human enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the two major causative agents for hand-foot-and-mouth disease (HFMD). Previously, we demonstrated that a virus-like particle (VLP) for EV71 produced from Saccharomyces cerevisiae is a potential vaccine candidate against EV71 infection, and an EV...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00422-15
更新日期:2015-06-01 00:00:00
abstract::Corynebacteriophages beta and gamma are closely related but heteroimmune; hence, gamma reproduces in C7(beta). A series of gamma mutants, designated gamma-bin (beta-inhibited), has been isolated. They reproduce in only 2 to 14% of infected C7(beta) cells, and, as a result, plaque with an efficiency of 10(-4) to 10(-5)...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.28.1.28-33.1978
更新日期:1978-10-01 00:00:00