Publications

TitleAbstractYear(sorted descending)
Filter
PMID
Filter
enhancement of adherence of helicobacter pylori to host cells by virus: possible mechanism of development of symptoms of gastric disease.it remains unclear why gastric disease does not develop in all cases of helicobacter pylori infection. in this study, we analyzed whether simian virus 5 (sv5) enhanced adherence of h. pylori to adenocarcinoma epithelial cells (ags). h. pylori in ags (harboring sv5) and sv5-infected vero cells, and an agglutination of h. pylori mixed with sv5 were observed by light microscopy, scanning and transmission electron microscopies. the adherent rate of h. pylori to sv5-infected vero cells and treated wi ...201728283804
a single dose recombinant piv5 expressing respiratory syncytial virus f and g proteins protected cotton rats and african green monkeys from rsv challenge.human respiratory syncytial virus (rsv) is a common cause of severe respiratory disease among infants, immunocompromised individuals and the elderly. no licensed vaccine is currently available. in this study, we evaluated two parainfluenza virus 5 (piv5)-vectored vaccines expressing rsv f (piv5/f) or g (piv5/g) proteins in the cotton rat and african green monkey models for their replication, immunogenicity and efficacy of protection against rsv challenge. following a single intranasal inoculatio ...201728298602
first complete genome sequence of parainfluenza virus 5 isolated from lesser panda.parainfluenza virus 5 (piv5) is widespread in mammals and humans. up to now, there is little information about piv5 infection in lesser pandas. in this study, a piv5 variant (named zjq-221) was isolated from a lesser panda with respiratory disease in guangzhou zoo in guangdong province, southern china. the full-length genome of zjq-221 was found to be 15,246 nucleotides and consisted of seven non-overlapping genes encoding eight proteins (i.e., np, v, p, m, f, sh, hn and l). sequence alignment a ...201728138777
the genetic stability of piv5-vectored rsv vaccine candidates after in vitro and in vivo passage.human respiratory syncytial virus (rsv) is the leading etiologic agent of lower respiratory tract infections in children, but no licensed vaccine exists. previously, our laboratory developed two parainfluenza virus 5 (piv5)-based rsv vaccine candidates that protect mice against rsv challenge. piv5 was engineered to express either the rsv fusion protein (f) or the rsv major attachment glycoprotein (g) between the hn and l genes of the piv5 genome [piv5-rsv-f (hn-l) or piv5-rsv-g (hn-l)]. to inves ...201728747497
parainfluenza virus 5 (piv5) expressing wild-type or pre-fusion respiratory syncytial virus (rsv) fusion protein protect mice and cotton rats from rsv challenge.human respiratory syncytial virus (rsv) is the leading cause of pediatric bronchiolitis and hospitalizations. rsv can also cause severe complications in elderly and immunocompromised individuals. there is no licensed vaccine. we previously generated a piv5-vectored vaccine candidate expressing the rsv fusion protein (f) that was immunogenic and protective in mice. in this work, our goal was to improve the original vaccine candidate by modifying the piv5 vector or by modifying the rsv-f antigen. ...201728747496
isolation and genomic characterization of a canine parainfluenza virus type 5 strain in china.a canine parainfluenza virus type 5 strain was isolated from a lung sample from a diseased dog. the genome sequene of this isolate, named hen0718, was determined and compared tho those of other previously reported canine parainfluenza viruses. unlike previously reported viruses, the hen0718 strain contained several nucleotide mutations in the sh gene that led to a frame shift in the open reading frame. phylogenetic analysis based on the complete virus genome and the p, f, and hn genes showed tha ...201728455668
exploring the virome of cattle with non-suppurative encephalitis of unknown etiology by metagenomics.non-suppurative encephalitis is one of the most frequent pathological diagnosis in cattle with neurological disease, but there is a gap in the knowledge on disease-associated pathogens. in order to identify viruses that are associated with non-suppurative encephalitis in cattle, we used a viral metagenomics approach on a sample set of 16 neurologically-diseased cows. we detected six virus candidates: parainfluenza virus 5 (piv-5), bovine astrovirus ch13/neuros1 (boastv-ch13/neuros1), bovine poly ...201626994586
solid-state nuclear magnetic resonance investigation of the structural topology and lipid interactions of a viral fusion protein chimera containing the fusion peptide and transmembrane domain.the fusion peptide (fp) and transmembrane domain (tmd) of viral fusion proteins play important roles during virus-cell membrane fusion, by inducing membrane curvature and transient dehydration. the structure of the water-soluble ectodomain of viral fusion proteins has been extensively studied crystallographically, but the structures of the fp and tmd bound to phospholipid membranes are not well understood. we recently investigated the conformations and lipid interactions of the separate fp and t ...201627766858
parainfluenza virus 5 upregulates cd55 expression to produce virions with enhanced resistance to complement-mediated neutralization.many enveloped rna viruses recruit host cell proteins during assembly as a mechanism to limit antiviral effects of complement. using viruses which incorporated cd46 alone, cd55 alone or both cd46 and cd55, we addressed the role of these two host cell regulators in limiting complement-mediated neutralization of parainfluenza virus 5 (piv5). piv5 incorporated functional forms of both cd55 and cd46 into virions. piv5 containing cd55 was highly resistant to complement-mediated neutralization, wherea ...201627505156
genome sequence of the parainfluenza virus 5 strain that persistently infects ags cells.we have sequenced the parainfluenza virus 5 strain that persistently infects the commonly used ags human cell line without causing cytopathology. this virus is most closely related to human strains, indicating that it may have originated from biopsy material or from laboratory contamination during generation of the cell line.201627445371
parainfluenza virus chimeric mini-replicons indicate a novel regulatory element in the leader promoter.gene expression of paramyxoviruses is regulated by genome-encoded cis-acting elements; however, whether all the required elements for viral growth have been identified is not clear. using a mini-replicon system, it has been shown that human parainfluenza virus type 2 (hpiv2) polymerase can recognize the promoter elements of parainfluenza virus type 5 (piv5), but reporter activity is lower in this case. we constructed a series of luciferase-encoding chimeric piv2/5 mini-genomes that are basically ...201627072881
flexibility of the head-stalk linker domain of paramyxovirus hn glycoprotein is essential for triggering virus fusion.the paramyxoviridae comprise a large family of enveloped, negative-sense, single-stranded rna viruses with significant economic and public health implications. for nearly all paramyxoviruses, infection is initiated by fusion of the viral and host cell plasma membranes in a ph-independent fashion. fusion is orchestrated by the receptor binding protein hemagglutinin-neuraminidase (hn; also called h or g depending on the virus type) protein and a fusion (f) protein, the latter undergoing a major re ...201627489276
immobilization of the n-terminal helix stabilizes prefusion paramyxovirus fusion proteins.parainfluenza virus 5 (piv5) is an enveloped, single-stranded, negative-sense rna virus of the paramyxoviridae family. piv5 fusion and entry are mediated by the coordinated action of the receptor-binding protein, hemagglutinin-neuraminidase (hn), and the fusion protein (f). upon triggering by hn, f undergoes an irreversible atp- and ph-independent conformational change, going down an energy gradient from a metastable prefusion state to a highly stable postfusion state. previous studies have high ...201627335462
c-terminal dxd-containing sequences within paramyxovirus nucleocapsid proteins determine matrix protein compatibility and can direct foreign proteins into budding particles.paramyxovirus particles are formed by a budding process coordinated by viral matrix (m) proteins. m proteins coalesce at sites underlying infected cell membranes and induce other viral components, including viral glycoproteins and viral ribonucleoprotein complexes (vrnps), to assemble at these locations from which particles bud. m proteins interact with the nucleocapsid (np or n) components of vrnps, and these interactions enable production of infectious, genome-containing virions. for the param ...201626792745
structure and stabilization of the hendra virus f glycoprotein in its prefusion form.hendra virus (hev) is one of the two prototypical members of the henipavirus genus of paramyxoviruses, which are designated biosafety level 4 (bsl-4) organisms due to the high mortality rate of nipah virus (niv) and hev in humans. paramyxovirus cell entry is mediated by the fusion protein, f, in response to binding of a host receptor by the attachment protein. during posttranslational processing, the fusion peptide of f is released and, upon receptor-induced triggering, inserts into the host cel ...201626712026
characterization of the variability of epstein-barr virus genes in nasopharyngeal biopsies: potential predictors for carcinoma progression.epstein-barr virus (ebv) infection is a significant factor in the pathogenesis of nasopharyngeal carcinoma, especially in the undifferentiated carcinoma of nasopharyngeal type (ucnt, world health organization type iii), which is the dominant histopathological type in high-risk areas. the major ebv oncogene is latent membrane protein 1 (lmp1). lmp1 gene shows variability with different tumorigenic and immunogenic potentials. ebv nuclear antigen 1 (ebna1) regulates progression of ebv-related tumor ...201627071030
human ifit1 inhibits mrna translation of rubulaviruses but not other members of the paramyxoviridae family.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 the translation of piv5 mrnas. here we report that while piv2, piv5, and mumps virus (muv) are sensitive to ifit1, nonrubulavirus members of the paramyxoviridae such as piv3, sendai virus (sev), and canine distemper virus (cdv) are resistant. the ifit1 sensitivity of piv5 was not rescued by coinfection with an ifit1 ...201627512068
releasing the genomic rna sequestered in the mumps virus nucleocapsid.in a negative strand rna virus, the genomic rna is sequestered inside the nucleocapsid when the viral rna-dependent rna polymerase uses it as the template for viral rna synthesis. it must require a conformational change in the nucleocapsid protein (np) to make the rna accessible by the viral polymerase during this process. the structure of an empty mumps virus nucleocapsid-like particle is determined to 10.4 å resolution by cryoem image reconstruction. by modeling the crystal structure of parain ...201627581981
analysis of cathepsin and furin proteolytic enzymes involved in viral fusion protein activation in cells of the bat reservoir host.bats of different species play a major role in the emergence and transmission of highly pathogenic viruses including ebola virus, sars-like coronavirus and the henipaviruses. these viruses require proteolytic activation of surface envelope glycoproteins needed for entry, and cellular cathepsins have been shown to be involved in proteolysis of glycoproteins from these distinct virus families. very little is currently known about the available proteases in bats. to determine whether the utilizatio ...201525706132
molecular characteristics of canine parainfluenza viruses type 5 (cpiv-5) isolated in korea.three canine parainfluenza viruses type 5 (cpiv-5) were isolated from lung tissues of 3 korean dogs with mild pneumonia between 2008 and 2009. the isolates were fully sequenced and compared with published reference sequences. the size of the genome was 15 246 nucleotides long and no remarkable differences were found when compared with previously published reference sequences. in phylogenetic analysis based on the f and p genes, parainfluenza virus 5 (piv-5) strains were divided into at least 3 s ...201525673911
rnasek is required for internalization of diverse acid-dependent viruses.viruses must gain entry into cells to establish infection. in general, viruses enter either at the plasma membrane or from intracellular endosomal compartments. viruses that use endosomal pathways are dependent on the cellular factors that control this process; however, these genes have proven to be essential for endogenous cargo uptake, and thus are of limited value for therapeutic intervention. the identification of genes that are selectively required for viral uptake would make appealing drug ...201526056282
viral fusion protein transmembrane domain adopts β-strand structure to facilitate membrane topological changes for virus-cell fusion.the c-terminal transmembrane domain (tmd) of viral fusion proteins such as hiv gp41 and influenza hemagglutinin (ha) is traditionally viewed as a passive α-helical anchor of the protein to the virus envelope during its merger with the cell membrane. the conformation, dynamics, and lipid interaction of these fusion protein tmds have so far eluded high-resolution structure characterization because of their highly hydrophobic nature. using magic-angle-spinning solid-state nmr spectroscopy, we show ...201526283363
influenza a virus uses intercellular connections to spread to neighboring cells.in the extracellular environment, cell-free virions seek out naive host cells over long distances and between organisms. this is the primary mechanism of spread for most viruses. here we provide evidence for an alternative pathway previously undescribed for orthomyxoviruses, whereby the spread of influenza a virus (iav) infectious cores to neighboring cells can occur within intercellular connections. the formation of these connections requires actin dynamics and is enhanced by viral infection. c ...201525428869
efficacy of parainfluenza virus 5 (piv5)-based tuberculosis vaccines in mice.mycobacterium tuberculosis, the etiological agent of tuberculosis (tb), is an important human pathogen. bacillus calmette-guérin (bcg), a live, attenuated variant of mycobacterium bovis, is currently the only available tb vaccine despite its low efficacy against the infectious pulmonary form of the disease in adults. thus, a more-effective tb vaccine is needed. parainfluenza virus 5 (piv5), a paramyxovirus, has several characteristics that make it an attractive vaccine vector. it is safe, inexpe ...201526552000
identification of two essential aspartates for polymerase activity in parainfluenza virus l protein by a minireplicon system expressing secretory luciferase.gene expression of nonsegmented negative-strand rna viruses (nsnsvs) such as parainfluenza viruses requires the rna synthesis activity of their polymerase l protein; however, the detailed mechanism of this process is poorly understood. in this study, a parainfluenza minireplicon assay expressing secretory gaussia luciferase (gluc) was established to analyze large protein (l) activity. measurement of gluc expression in the culture medium of cells transfected with the minigenome and viral polymera ...201526446904
regulation of viral rna synthesis by the v protein of parainfluenza virus 5.paramyxoviruses include many important animal and human pathogens. the genome of parainfluenza virus 5 (piv5), a prototypical paramyxovirus, encodes a v protein that inhibits viral rna synthesis. in this work, the mechanism of inhibition was investigated. using mutational analysis and a minigenome system, we identified regions in the n and c termini of the v protein that inhibit viral rna synthesis: one at the very n terminus of v and the second at the c terminus of v. furthermore, we determined ...201526378167
the nectin-4/afadin protein complex and intercellular membrane pores contribute to rapid spread of measles virus in primary human airway epithelia.the discovery that measles virus (mv) uses the adherens junction protein nectin-4 as its epithelial receptor provides a new vantage point from which to characterize its rapid spread in the airway epithelium. we show here that in well-differentiated primary cultures of airway epithelial cells from human donors (hae), mv infectious centers form rapidly and become larger than those of other respiratory pathogens: human respiratory syncytial virus, parainfluenza virus 5, and sendai virus. while visi ...201525926640
efficacy of a parainfluenza virus 5 (piv5)-based h7n9 vaccine in mice and guinea pigs: antibody titer towards ha was not a good indicator for protection.h7n9 has caused fatal infections in humans. a safe and effective vaccine is the best way to prevent large-scale outbreaks in the human population. parainfluenza virus 5 (piv5), an avirulent paramyxovirus, is a promising vaccine vector. in this work, we generated a recombinant piv5 expressing the ha gene of h7n9 (piv5-h7) and tested its efficacy against infection with influenza virus a/anhui/1/2013 (h7n9) in mice and guinea pigs. piv5-h7 protected the mice against lethal h7n9 challenge. interesti ...201525803697
parainfluenza virus 5 as possible cause of severe respiratory disease in calves, china. 201526583313
structure of the paramyxovirus parainfluenza virus 5 nucleoprotein-rna complex.parainfluenza virus 5 (piv5) is a member of the paramyxoviridae family of membrane-enveloped viruses with a negative-sense rna genome that is packaged and protected by long filamentous nucleocapsid-helix structures (rnps). these rnps, consisting of ∼2,600 protomers of nucleocapsid (n) protein, form the template for viral transcription and replication. we have determined the 3d x-ray crystal structure of the nucleoprotein (n)-rna complex from piv5 to 3.11-å resolution. the structure reveals a 13- ...201525831513
on the stability of parainfluenza virus 5 f proteins.the crystal structure of the f protein (prefusion form) of the paramyxovirus parainfluenza virus 5 (piv5) wr isolate was determined. we investigated the basis by which point mutations affect fusion in piv5 isolates w3a and wr, which differ by two residues in the f ectodomain. the p22 stabilizing site acts through a local conformational change and a hydrophobic pocket interaction, whereas the s443 destabilizing site appears sensitive to both conformational effects and amino acid charge/polarity c ...201525589638
parainfluenza virus 5 expressing the g protein of rabies virus protects mice after rabies virus infection.rabies remains a major public health threat around the world. once symptoms appear, there is no effective treatment to prevent death. in this work, we tested a recombinant parainfluenza virus 5 (piv5) strain expressing the glycoprotein (g) of rabies (piv5-g) as a therapy for rabies virus infection: we have found that piv5-g protected mice as late as 6 days after rabies virus infection. piv5-g is a promising vaccine for prevention and treatment of rabies virus infection.201525552723
probing the paramyxovirus fusion (f) protein-refolding event from pre- to postfusion by oxidative footprinting.to infect a cell, the paramyxoviridae family of enveloped viruses relies on the coordinated action of a receptor-binding protein (variably hn, h, or g) and a more conserved metastable fusion protein (f) to effect membrane fusion and allow genomic transfer. upon receptor binding, hn (h or g) triggers f to undergo an extensive refolding event to form a stable postfusion state. little is known about the intermediate states of the f refolding process. here, a soluble form of parainfluenza virus 5 f ...201424927585
paramyxovirus v protein interaction with the antiviral sensor lgp2 disrupts mda5 signaling enhancement but is not relevant to lgp2-mediated rlr signaling inhibition.the interferon antiviral system is a primary barrier to virus replication triggered upon recognition of nonself rnas by the cytoplasmic sensors encoded by retinoic acid-inducible gene i (rig-i), melanoma differentiation-associated gene 5 (mda5), and laboratory of genetics and physiology gene 2 (lgp2). paramyxovirus v proteins are interferon antagonists that can selectively interact with mda5 and lgp2 through contact with a discrete helicase domain region. interaction with mda5, an activator of a ...201424829334
stability of the parainfluenza virus 5 genome revealed by deep sequencing of strains isolated from different hosts and following passage in cell culture.the strain diversity of a rubulavirus, parainfluenza virus 5 (piv5), was investigated by comparing 11 newly determined and 6 previously published genome sequences. these sequences represent 15 piv5 strains, of which 6 were isolated from humans, 1 was from monkeys, 2 were from pigs, and 6 were from dogs. strain diversity is remarkably low, regardless of host, year of isolation, or geographical origin; a total of 7.8% of nucleotides are variable, and the average pairwise difference between strains ...201424453358
rig-i-like receptors evolved adaptively in mammals, with parallel evolution at lgp2 and rig-i.rig-i-like receptors (rlrs) are nucleic acid sensors that activate antiviral innate immune response. these molecules recognize diverse non-self rna substrates and are antagonized by several viral inhibitors. we performed an evolutionary analysis of rlr genes (rig-i, mda5, and lgp2) in mammals. results indicated that purifying selection had a dominant role in driving the evolution of rlrs. however, application of maximum-likelihood analyses identified several positions that evolved adaptively. po ...201424211720
a respiratory syncytial virus (rsv) vaccine based on parainfluenza virus 5 (piv5).human respiratory syncytial virus (rsv) is a leading cause of severe respiratory disease and hospitalizations in infants and young children. it also causes significant morbidity and mortality in elderly and immune compromised individuals. no licensed vaccine currently exists. parainfluenza virus 5 (piv5) is a paramyxovirus that causes no known human illness and has been used as a platform for vector-based vaccine development. to evaluate the efficacy of piv5 as a rsv vaccine vector, we generated ...201424717150
mutations in the fpiv motif of newcastle disease virus matrix protein attenuate virus replication and reduce virus budding.the fpiv-like late domains identified in the matrix (m) proteins of parainfluenza virus 5 and mumps virus have been demonstrated to be critical for virus budding. in this study, we found that the same fpiv sequence motif is present in the n-terminus of the newcastle disease virus (ndv) m protein. mutagenesis experiments demonstrated that mutation of either phenylalanine (f) or proline (p) to alanine led to a more obvious decrease in viral virulence and replication and resulted in poor budding of ...201424477785
fusion activation through attachment protein stalk domains indicates a conserved core mechanism of paramyxovirus entry into cells.paramyxoviruses are a large family of membrane-enveloped negative-stranded rna viruses causing important diseases in humans and animals. two viral integral membrane glycoproteins (fusion [f] and attachment [hn, h, or g]) mediate a concerted process of host receptor recognition, followed by the fusion of viral and cellular membranes, resulting in viral nucleocapsid entry into the cytoplasm. however, the sequence of events that closely links the timing of receptor recognition by hn, h, or g and th ...201424453369
the neutralizing capacity of antibodies elicited by parainfluenza virus infection of african green monkeys is dependent on complement.the african green monkey (agm) model was used to analyze the role of complement in neutralization of parainfluenza virus. parainfluenza virus 5 (piv5) and human parainfluenza virus type 2 were effectively neutralized in vitro by naïve agm sera, but neutralizing capacity was lost by heat-inactivation. the mechanism of neutralization involved formation of massive aggregates, with no evidence of virion lysis. following inoculation of the respiratory tract with a piv5 vector expressing hiv gp160, ag ...201425010267
activation of paramyxovirus membrane fusion and virus entry.the paramyxoviruses represent a diverse virus family responsible for a wide range of human and animal diseases. in contrast to other viruses, such as hiv and influenza virus, which use a single glycoprotein to mediate host receptor binding and virus entry, the paramyxoviruses require two distinct proteins. one of these is an attachment glycoprotein that binds receptor, while the second is a fusion glycoprotein, which undergoes conformational changes that drive virus-cell membrane fusion and viru ...201424530984
viral aetiology and clinical outcomes in hospitalised infants presenting with respiratory distress.to determine the prevalence of various types of viruses in infants hospitalised due to respiratory distress, compare molecular diagnostic tests and evaluate symptom severity.201424606114
point mutations in the paramyxovirus f protein that enhance fusion activity shift the mechanism of complement-mediated virus neutralization.parainfluenza virus 5 (piv5) activates and is neutralized by the alternative pathway (ap) in normal human serum (nhs) but not by heat-inactivated (hi) serum. we have tested the relationship between the fusion activity within the piv5 f protein, the activation of complement pathways, and subsequent complement-mediated virus neutralization. recombinant piv5 viruses with enhanced fusion activity were generated by introducing point mutations in the f fusogenic peptide (g3a) or at a distal site near ...201323785199
single-dose vaccination of a recombinant parainfluenza virus 5 expressing np from h5n1 virus provides broad immunity against influenza a viruses.influenza viruses often evade host immunity via antigenic drift and shift despite previous influenza virus infection and/or vaccination. vaccines that match circulating virus strains are needed for optimal protection. development of a universal influenza virus vaccine providing broadly cross-protective immunity will be of great importance. the nucleoprotein (np) of influenza a virus is highly conserved among all strains of influenza a viruses and has been explored as an antigen for developing a ...201323514880
structure of the parainfluenza virus 5 (piv5) hemagglutinin-neuraminidase (hn) ectodomain.paramyxoviruses cause a wide variety of human and animal diseases. they infect host cells using the coordinated action of two surface glycoproteins, the receptor binding protein (hn, h, or g) and the fusion protein (f). hn binds sialic acid on host cells (hemagglutinin activity) and hydrolyzes these receptors during viral egress (neuraminidase activity, na). additionally, receptor binding is thought to induce a conformational change in hn that subsequently triggers major refolding in homotypic f ...201323950713
[metagenomics-based detection of swine viruses].extreme varieties of viruses exist in the environment and animals, some of which are unknown. however, many unknown viruses are barely detected by means of conventional virus isolation and pcr assay.201323627112
efficacy of parainfluenza virus 5 mutants expressing hemagglutinin from h5n1 influenza a virus in mice.parainfluenza virus 5 (piv5) is a promising viral vector for vaccine development. piv5 is safe, stable, efficacious, cost-effective to produce and, most interestingly, it overcomes preexisting antivector immunity. we have recently reported that piv5 expressing the hemagglutinin (ha) from highly pathogenic avian influenza (hpai) virus h5n1 (piv5-h5) provides sterilizing immunity against lethal doses of hpai h5n1 infection in mice. it is thought that induction of apoptosis can lead to enhanced ant ...201323804633
recombinant parainfluenza virus 5 vaccine encoding the influenza virus hemagglutinin protects against h5n1 highly pathogenic avian influenza virus infection following intranasal or intramuscular vaccination of balb/c mice.new approaches for vaccination to prevent influenza virus infection are needed. emerging viruses, such as the h5n1 highly pathogenic avian influenza (hpai) virus, pose not only pandemic threats but also challenges in vaccine development and production. parainfluenza virus 5 (piv5) is an appealing vector for vaccine development, and we have previously shown that intranasal immunization with piv5 expressing the hemagglutinin from influenza virus was protective against influenza virus challenge (s. ...201323077318
recombinant parainfluenza virus 5 expressing hemagglutinin of influenza a virus h5n1 protected mice against lethal highly pathogenic avian influenza virus h5n1 challenge.a safe and effective vaccine is the best way to prevent large-scale highly pathogenic avian influenza virus (hpai) h5n1 outbreaks in the human population. the current fda-approved h5n1 vaccine has serious limitations. a more efficacious h5n1 vaccine is urgently needed. parainfluenza virus 5 (piv5), a paramyxovirus, is not known to cause any illness in humans. piv5 is an attractive vaccine vector. in our studies, a single dose of a live recombinant piv5 expressing a hemagglutinin (ha) gene of h5n ...201323077314
mutations in the parainfluenza virus 5 fusion protein reveal domains important for fusion triggering and metastability.paramyxovirus membrane glycoproteins f (fusion protein) and hn, h, or g (attachment protein) are critical for virus entry, which occurs through fusion of viral and cellular envelopes. the f protein folds into a homotrimeric, metastable prefusion form that can be triggered by the attachment protein to undergo a series of structural rearrangements, ultimately folding into a stable postfusion form. in paramyxovirus-infected cells, the f protein is activated in the golgi apparatus by cleavage adjace ...201324089572
characterization in vitro and in vivo of a novel porcine parainfluenza virus 5 isolate in korea.a novel porcine parainfluenza 5 (ppiv5), knu-11, in the genus rubulavirus of the subfamily paramyxovirinae, was isolated from the lung of a piglet in korea in 2011. to understand the importance of this virus as an infectious agent, in vitro and in vivo characteristics of knu-11 virus was investigated. knu-11 was remarkably cytopathogenic, showing distinct cell rounding and clumping evident in porcine alveolar macrophage (pam), porcine kidney (pk-15), and swine testicle (st) cells within 12h post ...201324050998
complete genome sequence of a novel porcine parainfluenza virus 5 isolate in korea.a novel cytopathogenic paramyxovirus was isolated from a lung sample from a piglet, using continuous porcine alveolar macrophage cells. morphologic and genetic studies indicated that this porcine virus (ppiv5) belongs to the species parainfluenza 5 in the family paramyxoviridae. we attempted to determine the complete nucleotide sequence of the first korean ppiv5 isolate, designated knu-11. the full-length genome of knu-11 was found to be 15,246 nucleotides in length and consist of seven nonoverl ...201323807746
full conversion of the hemagglutinin-neuraminidase specificity of the parainfluenza virus 5 fusion protein by replacement of 21 amino acids in its head region with those of the simian virus 41 fusion protein.for most parainfluenza viruses, a virus type-specific interaction between the hemagglutinin-neuraminidase (hn) and fusion (f) proteins is a prerequisite for mediating virus-cell fusion and cell-cell fusion. the molecular basis of this functional interaction is still obscure partly because it is unknown which region of the f protein is responsible for the physical interaction with the hn protein. our previous cell-cell fusion assay using the chimeric f proteins of parainfluenza virus 5 (piv5) and ...201323698295
deep sequencing analysis of defective genomes of parainfluenza virus 5 and their role in interferon induction.preparations of parainfluenza virus 5 (piv5) that are potent activators of the interferon (ifn) induction cascade were generated by high-multiplicity passage in order to accumulate defective interfering virus genomes (dis). nucleocapsid rna from these virus preparations was extracted and subjected to deep sequencing. sequencing data were analyzed using methods designed to detect internal deletion and "copyback" dis in order to identify and characterize the different dis present and to approximat ...201323449801
membrane-dependent conformation, dynamics, and lipid interactions of the fusion peptide of the paramyxovirus piv5 from solid-state nmr.the entry of enveloped viruses into cells requires protein-catalyzed fusion of the viral and cell membranes. the structure-function relation of a hydrophobic fusion peptide (fp) in viral fusion proteins is still poorly understood. we report magic-angle-spinning solid-state nmr results of the membrane-bound conformation, dynamics, and lipid interactions of the fp of the f protein of the paramyxovirus, parainfluenza virus 5 (piv5). (13)c chemical shifts indicate that the piv5 fp structure depends ...201323183373
structure of the cleavage-activated prefusion form of the parainfluenza virus 5 fusion protein.the paramyxovirus parainfluenza virus 5 (piv5) enters cells by fusion of the viral envelope with the plasma membrane through the concerted action of the fusion (f) protein and the receptor binding protein hemagglutinin-neuraminidase. the f protein folds initially to form a trimeric metastable prefusion form that is triggered to undergo large-scale irreversible conformational changes to form the trimeric postfusion conformation. it is thought that f refolding couples the energy released with memb ...201223012473
fusion activation by a headless parainfluenza virus 5 hemagglutinin-neuraminidase stalk suggests a modular mechanism for triggering.the paramyxoviridae family of enveloped viruses enters cells through the concerted action of two viral glycoproteins. the receptor-binding protein, hemagglutinin-neuraminidase (hn), h, or g, binds its cellular receptor and activates the fusion protein, f, which, through an extensive refolding event, brings viral and cellular membranes together, mediating virus-cell fusion. however, the underlying mechanism of f activation on receptor engagement remains unclear. current hypotheses propose conform ...201222949640
base of the measles virus fusion trimer head receives the signal that triggers membrane fusion.the measles virus (mv) fusion (f) protein trimer executes membrane fusion after receiving a signal elicited by receptor binding to the hemagglutinin (h) tetramer. where and how this signal is received is understood neither for mv nor for other paramyxoviruses. because only the prefusion structure of the parainfluenza virus 5 (piv5) f-trimer is available, to study signal receipt by the mv f-trimer, we generated and energy-refined a homology model. we used two approaches to predict surface residue ...201222859308
cd8 marks a subpopulation of lung-derived dendritic cells with differential responsiveness to viral infection and toll-like receptor stimulation.an increasing number of studies suggest that individual subsets of dendritic cells (dc) exhibit distinct capabilities with regard to the generation of the adaptive immune response. in this study, we evaluated the properties of a relatively unexplored dc subset present in the lung-draining mediastinal lymph node. this subset expresses the airway dendritic cell marker cd103 together with cd8. these dc were of interest given that our previous studies using a model of respiratory infection with vacc ...201222811544
paramyxovirus v proteins interact with the rna helicase lgp2 to inhibit rig-i-dependent interferon induction.rig-i and mda-5 are activated by viral rna and stimulate type i interferon production. laboratory of genetics and physiology 2 (lgp2) shares homology with rig-i and mda-5 but lacks the card domains required for signaling. the v proteins of paramyxoviruses limit interferon induction by binding mda-5 and preventing its activation; however, they do not bind rig-i and have not been considered inhibitors of rig-i signaling. here we uncover a novel mechanism of rig-i inhibition in which the v protein ...201222301134
mumps virus inhibits migration of primary human macrophages toward a chemokine gradient through a tnf-alpha dependent mechanism.macrophages are an important cell type for regulation of immunity, and can play key roles in virus pathogenesis. here we address the effect of infection of primary human macrophages with the related paramyxoviruses parainfluenza virus 5 (piv5) and mumps virus (muv). monocyte-derived macrophages infected with piv5 or muv showed very little cytopathic effect, but were found to be defective in migration toward a gradient of chemokines such as macrophage colony stimulating factor (mcsf) and vascular ...201222935226
evaluating a parainfluenza virus 5-based vaccine in a host with pre-existing immunity against parainfluenza virus 5.parainfluenza virus 5 (piv5), formerly known as simian virus 5 (sv5), is a paramyxovirus often referred to as canine parainfluenza virus (cpi) in the veterinary field. piv5 is thought to be a contributing factor to kennel cough. kennel cough vaccines containing live piv5 have been used in dogs for many decades. piv5 is not known to cause any diseases in humans or other animals. piv5 has been used as a vector for vaccine development for humans and animals. one critical question concerning the use ...201223185558
isg56/ifit1 is primarily responsible for interferon-induced changes to patterns of parainfluenza virus type 5 transcription and protein synthesis.interferon (ifn) induces an antiviral state in cells that results in alterations of the patterns and levels of parainfluenza virus type 5 (piv5) transcripts and proteins. this study reports that ifn-stimulated gene 56/ifn-induced protein with tetratricopeptide repeats 1 (isg56/ifit1) is primarily responsible for these effects of ifn. it was shown that treating cells with ifn after infection resulted in an increase in virus transcription but an overall decrease in virus protein synthesis. as ther ...201223052390
pathogens of wild maned wolves (chrysocyon brachyurus) in brazil.the maned wolf, chrysocyon brachyurus, is an endangered neotropical canid that survives at low population densities. diseases are a potential threat for its conservation but to date have been poorly studied. we performed clinical evaluations and investigated the presence of infectious diseases through serology and coprologic tests on maned wolves from galheiro natural private reserve, perdizes city, minas gerais state, southeastern brazil. fifteen wolves were captured between 2003 and 2008. we f ...201223060508
The chicken chorioallantoic membrane tumor assay as model for qualitative testing of oncolytic adenoviruses.Oncolytic adenoviruses are promising anticancer agents. To study and optimize their tumor-killing potency, genuine tumor models are required. Here we describe the use of the chicken chorioallantoic membrane (CAM) tumor model in studies on oncolytic adenoviral vectors. Suspensions of human melanoma, colorectal carcinoma and glioblastoma multiforme cell lines were grafted on the CAM of embryonated chicken eggs. All cell lines tested formed 5-10?mm size tumors, which recapitulated hallmarks of corr ...201222015640
role of ubiquitin in piv5 particle formation.ubiquitin is important for the budding of many retroviruses and other enveloped viruses, but the precise role for ubiquitin in virus budding remains unclear. here, we characterized ubiquitination of the matrix (m) protein of a paramyxovirus, parainfluenza virus 5 (piv5). piv5 m protein (but not piv5 nucleocapsid protein) was found to be targeted for monoubiquitination in transfected mammalian cells. major sites of ubiquitin attachment identified by mass spectrometry analysis were lysine residues ...201222258249
a novel rabies vaccine based on a recombinant parainfluenza virus 5 expressing rabies virus glycoprotein.untreated rabies virus (rabv) infection leads to death. vaccine and postexposure treatment have been effective in preventing rabv infection. however, due to cost, rabies vaccination and treatment have not been widely used in developing countries. there are 55,000 human death caused by rabies annually. an efficacious and cost-effective rabies vaccine is needed. parainfluenza virus 5 (piv5) is thought to contribute to kennel cough, and kennel cough vaccines containing live piv5 have been used in d ...201223269806
c-terminal tyrosine residues modulate the fusion activity of the hendra virus fusion protein.the paramyxovirus family includes important human pathogens such as measles, mumps, respiratory syncytial virus, and the recently emerged, highly pathogenic hendra and nipah viruses. the viral fusion (f) protein plays critical roles in infection, promoting both the virus-cell membrane fusion events needed for viral entry as well as cell-cell fusion events leading to syncytia formation. we describe the surprising finding that addition of the short epitope ha tag to the cytoplasmic tail (ct) of th ...201121175223
expression of paramyxovirus v proteins promotes replication and spread of hepatitis c virus in cultures of primary human fetal liver cells.here we demonstrate that primary cultures of human fetal liver cells (hflc) reliably support infection with laboratory strains of hepatitis c virus (hcv), although levels of virus replication vary significantly between different donor cell preparations and frequently decline in a manner suggestive of active viral clearance. to investigate possible contributions of the interferon (ifn) system to control hcv infection in hflc, we exploited the well-characterized ability of paramyxovirus (pmv) v pr ...201122144107
comparison of differing cytopathic effects in human airway epithelium of parainfluenza virus 5 (w3a), parainfluenza virus type 3, and respiratory syncytial virus.parainfluenza virus 5 (piv5) infects a wide range of animals including dogs, pigs, cats, and humans; however, its association with disease in humans remains controversial. in contrast to parainfluenza virus 3 (piv3) or respiratory syncytial virus (rsv), piv5 is remarkably non-cytopathic in monolayer cultures of immortalized epithelial cells. to compare the cytopathology produced by these viruses in a relevant human tissue, we infected an in vitro model of human ciliated airway epithelium and mea ...201121986028
Structure and mutagenesis of the parainfluenza virus 5 hemagglutinin-neuraminidase stalk domain reveals a four-helix bundle and the role of the stalk in fusion promotion.Paramyxovirus entry into cells requires the fusion protein (F) and a receptor binding protein (hemagglutinin-neuraminidase [HN], H, or G). The multifunctional HN protein of some paramyxoviruses, besides functioning as the receptor (sialic acid) binding protein (hemagglutinin activity) and the receptor-destroying protein (neuraminidase activity), enhances F activity, presumably by lowering the activation energy required for F to mediate fusion of viral and cellular membranes. Before or upon recep ...201121994464
activation of the beta interferon promoter by paramyxoviruses in the absence of virus protein synthesis.conflicting reports exist regarding the requirement for virus replication in interferon (ifn) induction by paramyxoviruses. our previous work has demonstrated that pathogen-associated molecular patterns capable of activating the ifn-induction cascade are not normally generated during virus replication, but are associated instead with the presence of defective interfering (di) viruses. we demonstrate here that dis of paramyxoviruses, including parainfluenza virus 5, mumps virus and sendai virus, ...201122049094
parainfluenza virus 5-based vaccine vectors expressing vaccinia virus (vacv) antigens provide long-term protection in mice from lethal intranasal vacv challenge.to test the potential for parainfluenza virus 5 (piv5)-based vectors to provide protection from vaccinia virus (vacv) infection, piv5 was engineered to express secreted vacv l1r and b5r proteins, two important antigens for neutralization of intracellular mature (imv) and extracellular enveloped (eev) virions, respectively. protection of mice from lethal intranasal vacv challenge required intranasal immunization with piv5-l1r/b5r in a prime-boost protocol, and correlated with low vacv-induced pat ...201121885079
Morphology and infectivity of virus that persistently caused infection in an AGS cell line.A recent report has indicated that proteins and genes of simian virus 5 (SV5) are detected in a human gastric adenocarcinoma (AGS) cell line, which is widely provided for oncology, immunology, and microbiology research. However, the production of infective virions has not been determined in this cell line. In this study, the morphology and infectivity of the virus particles of the AGS cell line were studied by light and electron microscopy and virus transmission assay. The virus particles were a ...201122179184
activation of ifn-β expression by a viral mrna through rnase l and mda5.ifns play a critical role in innate immunity against viral infections. melanoma differentiation-associated protein 5 (mda5), an rna helicase, is a key component in activating the expression of type i ifns in response to certain types of viral infection. mda5 senses noncellular rna and triggers the signaling cascade that leads to ifn production. synthetic double-stranded rnas are known activators of mda5. natural single-stranded rnas have not been reported to activate mda5, however. we have seren ...201121245317
identification of domains on the fusion (f) protein trimer that influence the hemagglutinin-neuraminidase specificity of the f protein in mediating cell-cell fusion.for most paramyxoviruses, virus type-specific interaction between fusion (f) protein and attachment protein (hemagglutinin-neuraminidase [hn], hemagglutinin [h], or glycoprotein [g]) is a prerequisite for mediating virus-cell fusion and cell-cell fusion. our previous cell-cell fusion assay using the chimeric f proteins of human parainfluenza virus 2 (hpiv2) and simian virus 41 (sv41) suggested that the middle region of the hpiv2 f protein contains the site(s) that determines its specificity for ...201121270148
synthesis and biological evaluation of analogues of akt (protein kinase b) inhibitor-iv.inhibitors of the pi3-kinase/akt (protein kinase b) pathway are under investigation as anticancer and antiviral agents. the benzimidazole derivative akt inhibitor-iv (chembridge 5233705) affects this pathway and exhibits potent anticancer and antiviral activity. to probe its biological activity, we synthesized akt inhibitor-iv and 21 analogues using a novel six-step route based on zrcl(4)-catalyzed cyclization of 1,2-arylenediamines with a,ß-unsaturated aldehydes. we examined effects on viabilit ...201121319800
transmembrane orientation and possible role of the fusogenic peptide from parainfluenza virus 5 (piv5) in promoting fusion.membrane fusion is required for diverse biological functions ranging from viral infection to neurotransmitter release. fusogenic proteins increase the intrinsically slow rate of fusion by coupling energetically downhill conformational changes of the protein to kinetically unfavorable fusion of the membrane-phospholipid bilayers. class i viral fusogenic proteins have an n-terminal hydrophobic fusion peptide (fp) domain, important for interaction with the target membrane, plus a c-terminal transme ...201121321234
failure to activate the ifn-β promoter by a paramyxovirus lacking an interferon antagonist.it is generally thought that pathogen-associated molecular patterns (pamps) responsible for triggering interferon (ifn) induction are produced during virus replication and, to limit the activation of the ifn response by these pamps, viruses encode antagonists of ifn induction. here we have studied the induction of ifn by parainfluenza virus type 5 (piv5) at the single-cell level, using a cell line expressing gfp under the control of the ifn-β promoter. we demonstrate that a recombinant piv5 (ter ...201121511322
are empiric antibiotics for acute exudative tonsillitis needed in children?background: empiric antibiotics are frequently given for children with acute exudative tonsillitis. a few studies have investigated the causative agent of acute "exudative" tonsillitis in children to evaluate the necessity of antibiotic therapy. this study tried to explore the common causative agent of acute exudative tonsillitis among children. methods: from april 2009 to march 2010, throat swabs were obtained and cultured for viruses and bacteria from children who visited the pediatric emergen ...201121524968
construction and biological characterisation of recombinant porcine circovirus type 2 expressing the v5 epitope tag.porcine circovirus type 2 (pcv2) is a major causal agent of post-weaning multisystemic wasting syndrome in piglets. to investigate the feasibility of pcv2 expressing an exogenous epitope, a 14-amino-acid v5 epitope derived from simian parainfluenza virus type 5, was inserted into the c terminus of the capsid protein. recombinant pcv2 expressing the v5 epitope, recpcv2/cl-v5, was rescued by transfecting an infectious clone into pk-15 cells and was characterised by an immunoperoxidase monolayer as ...201121641944
sumoylation of the p protein at k254 plays an important role in growth of parainfluenza virus 5 (piv5).the p protein of parainfluenza virus 5 (piv5) is an essential cofactor of the viral rna-dependent rna polymerase. phosphorylation of the p protein can positively or negatively regulate viral gene expression, depending on the precise phosphorylation sites. sumoylation, a process of adding small ubiquitin-like modifier (sumo) to proteins post-translationally, plays an important role in regulating protein function. in this study, we have found that the p protein of piv5 was sumoylated with sumo1 in ...201121795356
identification of a phosphorylation site within the p protein important for mrna transcription and growth of parainfluenza virus 5.the viral rna-dependent rna polymerase (vrdrp) of paramyxovirus consists of the large (l) protein and the phosphoprotein (p). p is heavily phosphorylated, and it is thought that the phosphorylation of p plays a role in regulating viral rna synthesis. however, no phosphorylation site within the p protein in paramyxovirus has been identified as playing a positive role in viral rna synthesis in virus infection. using mass spectrometry analysis, the threonine residue at position 286 of p of parainfl ...201121680523
The paramyxovirus fusion (F) protein C-terminal region: mutagenesis indicates an indivisible protein unit.Paramyxoviruses enter host cells by fusing the viral envelope with a host cell membrane. Fusion is mediated by the viral fusion (F) protein and it undergoes large irreversible conformational changes to cause membrane merger. The C-terminus of PIV5 F contains a membrane-proximal 7-residue external region (MPER), followed by the transmembrane (TM) domain and a 20-residue cytoplasmic tail. To study the sequence requirements of the F protein C-terminus for fusion, we constructed chimeras containing ...201122171273
activation of human macrophages by bacterial components relieves the restriction on replication of an interferon-inducing parainfluenza virus 5 (piv5) p/v mutant.macrophages regulate immune responses during many viral infections, and can be a major determinant of pathogenesis, virus replication and immune response to infection. here, we have addressed the question of the outcome of infection of primary human macrophages with parainfluenza virus 5 (piv5) and a piv5 mutant (p/v-cpi-) that is unable to counteract interferon (ifn) responses. in cultures of naïve monocyte-derived macrophages (mdms), wt piv5 established a highly productive infection, whereas t ...201021185944
viral pathogens associated with acute respiratory infections in central vietnamese children.hospitalized vietnamese children with acute respiratory infection were investigated for 13 viral pathogens using multiplex-polymerase chain reaction. we enrolled 958 children of whom 659 (69%) had documented viral infection: rhinovirus (28%), respiratory syncytial virus (23%), influenza virus (15%), adenovirus (5%), human metapneumo virus (4.5%), parainfluenza virus (5%), and bocavirus (2%). these vietnamese children had a range of respiratory viruses which underscores the need for enhanced acut ...201019907358
piv5 m protein interaction with host protein angiomotin-like 1.paramyxovirus matrix (m) proteins organize virus assembly, functioning as adapters that link together viral ribonucleoprotein complexes and viral glycoproteins at infected cell plasma membranes. m proteins may also function to recruit and manipulate host factors to assist virus budding, similar to retroviral gag proteins. by yeast two-hybrid screening, angiomotin-like 1 (amotl1) was identified as a host factor that interacts with the m protein of parainfluenza virus 5 (piv5). amotl1-m protein in ...201019932912
tlr3-dependent upregulation of rig-i leads to enhanced cytokine production from cells infected with the parainfluenza virus sv5.here we address the role of rig-i and tlr3 in differential cytokine responses against simian virus 5 (sv5) and two distinct cytokine inducing sv5 mutants. ifn-beta and il-6 secretion was induced by infection with p/v-cpi-, an sv5 mutant with p/v substitutions, and were reduced by either sirna-mediated knockdown of rig-i expression or by expression of a dsrna-binding protein. tlr3 overexpression did not alter cytokine secretion induced by p/v-cpi- or by le-(u5c, a14g), an sv5 promoter mutant. tlr ...201019948350
a promiscuous alpha-helical motif anchors viral hijackers and substrate receptors to the cul4-ddb1 ubiquitin ligase machinery.the cullin 4-dna-damage-binding protein 1 (cul4-ddb1) ubiquitin ligase machinery regulates diverse cellular functions and can be subverted by pathogenic viruses. here we report the crystal structure of ddb1 in complex with a central fragment of hepatitis b virus x protein (hbx), whose ddb1-binding activity is important for viral infection. the structure reveals that hbx binds ddb1 through an alpha-helical motif, which is also found in the unrelated paramyxovirus sv5-v protein despite their seque ...201019966799
phosphorylation of paramyxovirus phosphoprotein and its role in viral gene expression.paramyxoviruses include many important human and animal pathogens such as measles virus, mumps virus, human parainfluenza viruses, and respiratory syncytial virus, as well as emerging viruses such as nipah virus and hendra virus. the paramyxovirus rna-dependent rna polymerase consists of the phosphoprotein (p) and the large protein. both of these proteins are essential for viral rna synthesis. the p protein is phosphorylated at multiple sites, probably by more than one host kinase. while it is t ...201020020826
reciprocal regulation of akt and map kinase dictates virus-host cell fusion.viruses of the paramyxoviridae family bind to their host cells by using hemagglutinin-neuraminidase (hn), which enhances fusion protein (f)-mediated membrane fusion. although respiratory syncytial virus and parainfluenza virus 5 of this family are suggested to trigger host cell signaling during infection, the virus-induced intracellular signals dictating virus-cell fusion await elucidation. using an f- or hn-f-containing reconstituted envelope of sendai virus, another paramyxovirus, we revealed ...201020164223
enhanced oncolytic activity of vesicular stomatitis virus encoding sv5-f protein against prostate cancer.vesicular stomatitis virus has been investigated as an oncolytic agent for cancer therapy because it preferentially replicates in tumor but not in normal cells due to the lack of a robust interferon antiviral system in transformed cells. however, wild-type vesicular stomatitis virus can induce a strong systemic immunological response and replicate in the central nervous system, potentially limiting its clinical usefulness. we report the construction of the recombinant, replication restricted ves ...201020172545
structure of the newcastle disease virus f protein in the post-fusion conformation.the paramyxovirus f protein is a class i viral membrane fusion protein which undergoes a significant refolding transition during virus entry. previous studies of the newcastle disease virus, human parainfluenza virus 3 and parainfluenza virus 5 f proteins revealed differences in the pre- and post-fusion structures. the ndv queensland (q) f structure lacked structural elements observed in the other two structures, which are key to the refolding and fusogenic activity of f. here we present the ndv ...201020439109
the actin cytoskeleton inhibits pore expansion during piv5 fusion protein-promoted cell-cell fusion.paramyxovirus fusion (f) proteins promote both virus-cell fusion, required for viral entry, and cell-cell fusion, resulting in syncytia formation. we used the f-actin stabilizing drug, jasplakinolide, and the g-actin sequestrant, latrunculin a, to examine the role of actin dynamics in cell-cell fusion mediated by the parainfluenza virus 5 (piv5) f protein. jasplakinolide treatment caused a dose-dependent increase in cell-cell fusion as measured by both syncytia and reporter gene assays, and latr ...201020537366
replication-independent activation of human plasmacytoid dendritic cells by the paramyxovirus sv5 requires tlr7 and autophagy pathways.the paramyxovirus simian virus 5 (sv5) is a poor inducer of interferon (ifn) secretion in all cell types tested so far, including primary epithelial cells and primary human myeloid dendritic cells. sv5 is hypothesized to limit induction of antiviral responses through control of viral gene expression and production of the v protein antagonist. plasmacytoid dendritic cells (pdcs) are known to uniquely express toll-like receptor (tlr)-7 and are a main producer of ifn-alpha among peripheral blood mo ...201020605567
ifngamma-producing, virus-specific cd8+ effector cells acquire the ability to produce il-10 as a result of entry into the infected lung environment.it has become clear that t cells with the potential to negatively regulate the immune response are normal constituents of the immune system. these cells often mediate their effects through the production of immunosuppressive factors. at present our understanding of how these cells are generated is limited. here we report the presence of a population of il-10-producing, virus-specific cd8+ t cells in the lungs of mice following acute respiratory infection. these cells were only found at minimal l ...201020627346
a role for caveolin 1 in assembly and budding of the paramyxovirus parainfluenza virus 5.caveolin 1 (cav-1) is an integral membrane protein that forms the coat structure of plasma membrane caveolae and regulates caveola-dependent functions. caveolae are enriched in cholesterol and sphingolipids and are related to lipid rafts. many studies implicate rafts as sites of assembly and budding of enveloped virus. we show that cav-1 colocalizes with the paramyxovirus parainfluenza virus 5 (piv-5) nucleocapsid (np), matrix (m), and hemagglutinin-neuraminidase (hn) proteins. moreover, electro ...201020631121
analysis of parainfluenza virus-5 hemagglutinin-neuraminidase protein mutants that are blocked in internalization and degradation.the piv-5 hemagglutinin-neuraminidase (hn) protein is a multifunctional protein with sialic acid binding, neuraminidase and fusion promotion activity. hn is internalized by clathrin-mediated endocytosis and degraded. hn lacks internalization signals in its cytoplasmic tail but a single glutamic acid present at residue 37 at the putative transmembrane/ectodomain boundary is critical. we rescued rpiv-5 with mutations e37d or e37k, which have been shown to impair or abolish hn internalization, resp ...201020684967
interaction of mumps virus v protein variants with stat1-stat2 heterodimer: experimental and theoretical studies.mumps virus v protein has the ability to inhibit the interferon-mediated antiviral response by inducing degradation of stat proteins. two virus variants purified from urabe am9 mumps virus vaccine differ in their replication and transcription efficiency in cells primed with interferon. virus susceptibility to ifn was associated with insertion of a non-coded glycine at position 156 in the v protein (vgly) of one virus variant, whereas resistance to ifn was associated with preservation of wild-typ ...201020937132
the c-terminal end of parainfluenza virus 5 np protein is important for virus-like particle production and m-np protein interaction.enveloped virus particles are formed by budding from infected-cell membranes. for paramyxoviruses, viral matrix (m) proteins are key drivers of virus assembly and budding. however, other paramyxovirus proteins, including glycoproteins, nucleocapsid (np or n) proteins, and c proteins, are also important for particle formation in some cases. to investigate the role of np protein in parainfluenza virus 5 (piv5) particle formation, np protein truncation and substitution mutants were analyzed. altera ...201020943976
Refresh
firstprev
12345
nextlast
Displaying items 1 - 100 of 462