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chimeric human parainfluenza virus bearing the ebola virus glycoprotein as the sole surface protein is immunogenic and highly protective against ebola virus challenge.we generated a new live-attenuated vaccine against ebola virus (ebov) based on a chimeric virus hpiv3/deltaf-hn/ebogp that contains the ebov glycoprotein (gp) as the sole transmembrane envelope protein combined with the internal proteins of human parainfluenza virus type 3 (hpiv3). electron microscopy analysis of the virus particles showed that they have an envelope and surface spikes resembling those of ebov and a particle size and shape resembling those of hpiv3. when hpiv3/deltaf-hn/ebogp was ...200919010509
air leaks in children with acute bronchiolitis. 200819012637
a histidine switch in hemagglutinin-neuraminidase triggers paramyxovirus-cell membrane fusion.most paramyxovirus fusion proteins require coexpression of and activation by a homotypic attachment protein, hemagglutinin-neuraminidase (hn), to promote membrane fusion. however, the molecular mechanism of the activation remains unknown. we previously showed that the incorporation of a monohistidylated lipid into f-virosome (sendai viral envelope containing only fusion protein) enhanced its fusion to hepatocytes, suggesting that the histidine residue in the lipid accelerated membrane fusion. th ...200919052089
human piv-2 recombinant sendai virus (rsev) elicits durable immunity and combines with two additional rsevs to protect against hpiv-1, hpiv-2, hpiv-3, and rsv.the human parainfluenza viruses (hpivs) and respiratory syncytial viruses (rsvs) are the leading causes of hospitalizations due to respiratory viral disease in infants and young children, but no vaccines are yet available. here we describe the use of recombinant sendai viruses (rsevs) as candidate vaccine vectors for these respiratory viruses in a cotton rat model. two new sendai virus (sev)-based hpiv-2 vaccine constructs were generated by inserting the fusion (f) gene or the hemagglutinin-neur ...200919200447
human parainfluenza virus infection of the airway epithelium: viral hemagglutinin-neuraminidase regulates fusion protein activation and modulates infectivity.three discrete activities of the paramyxovirus hemagglutinin-neuraminidase (hn) protein, receptor binding, receptor cleaving (neuraminidase), and triggering of the fusion protein, each affect the promotion of viral fusion and entry. for human parainfluenza virus type 3 (hpiv3), the effects of specific mutations that alter these functions of the receptor-binding protein have been well characterized using cultured monolayer cells, which have identified steps that are potentially relevant to pathog ...200919386708
evidence for phosphorylation of human parainfluenza virus type 3 c protein: mutant c proteins exhibit variable inhibitory activities in vitro.the p mrna of human parainfluenza virus type 3, like other members of the subfamily paramyxovirinae, gives rise to several polypeptides, one amongst them, the c protein, which is involved in inhibition of viral rna synthesis as well as counteracting the host interferon signaling pathway. as a further step towards characterizing the function of c protein we present evidence to demonstrate the phosphorylation of c protein. evidence for this observation emerged from deletion mapping studies coupled ...200919410612
phase-i study medi-534, of a live, attenuated intranasal vaccine against respiratory syncytial virus and parainfluenza-3 virus in seropositive children.a live, attenuated respiratory syncytial virus and parainfluenza virus type 3 vaccine was evaluated in healthy respiratory syncytial virus/parainfluenza virus type 3 seropositive children aged 1 to 9 years. three cohorts of 40 children were randomized 1:1 to receive 10, 10, or 10 median tissue culture infectious dose50 medi-534 vaccine or placebo. the vaccine's safety profile was similar to placebo, no viral shedding was detected, and the vaccine was minimally immunogenic.200919483659
human bocavirus in children with respiratory tract infection in shanghai: a retrospective study.human bocavirus (hbov) was first reported in 2005. the worldwide presence of hbov in children with acute respiratory tract infection (arti) has been confirmed. this study aimed to understand the prevalence and clinical features of hbov in children with arti in shanghai and explore the causative implication of hbov in arti.201020143214
viral entry inhibitors targeted to the membrane site of action.the fusion of enveloped viruses with the host cell is driven by specialized fusion proteins to initiate infection. the "class i" fusion proteins harbor two regions, typically two heptad repeat (hr) domains, which are central to the complex conformational changes leading to fusion: the first heptad repeat (hrn) is adjacent to the fusion peptide, while the second (hrc) immediately precedes the transmembrane domain. peptides derived from the hr regions can inhibit fusion, and one hr peptide, t20 (e ...201020357085
a study of cytotoxicity of novel chlorokojic acid derivatives with their antimicrobial and antiviral activities.a series of 6-chloromethyl-3-hydroxy-2-substituted 4h-pyran-4-one derivatives were synthesized and tested for their antimicrobial and antiviral activities. mannich base derivatives were prepared through the reaction of substituted piperazine or piperidine derivatives on chlorokojic acid and formaline. the structures of the synthesized compounds were confirmed by ir, (1)h and (13)c nmr, esi-ms, and elemental analysis. according to the activity studies, compounds 2-7 (mic: 1-2 microg/ml) were foun ...201020591538
frequency of detection of upper respiratory tract viruses in patients tested for pandemic h1n1/09 viral infection.molecular testing of 270 consecutive nasopharyngeal swab samples taken in may and june 2009 and 274 samples from patients hospitalized between july and december 2009 showed similar findings of respiratory viruses, with influenza a pandemic virus h1n1/09 being the most represented, followed by human parainfluenza virus type 3 and rhinoviruses. statistical analyses suggested virus cocirculation in the absence of viral interference.201020592147
recent advances in ebolavirus vaccine development.ebolavirus is a highly infectious pathogen with a case fatality rate as high as 90%. currently there is a lack of licensed ebolavirus vaccines as well as pre- and post-exposure treatments. recent increases in the frequency of natural human ebolavirus infections and its potential use as a bioterrorism agent makes vaccine development a priority for many nations. significant progress has been made in understanding the pathogenesis of ebolavirus infection and several promising vaccine candidates wer ...201020671437
bradykinin-induced lung inflammation and bronchoconstriction: role in parainfluenze-3 virus-induced inflammation and airway hyperreactivity.inhaled bradykinin causes bronchoconstriction in asthmatic subjects but not nonasthmatics. to date, animal studies with inhaled bradykinin have been performed only in anesthetized guinea pigs and rats, where it causes bronchoconstriction through sensory nerve pathways. in the present study, airway function was recorded in conscious guinea pigs by whole-body plethysmography. inhaled bradykinin (1 mm, 20 s) caused bronchoconstriction and influx of inflammatory cells to the lungs, but only when the ...201020847038
human parainfluenza virus type 3 (hpiv 3) viral community-acquired pneumonia (cap) mimicking swine influenza (h1n1) during the swine flu pandemic.the swine influenza (h1n1) pandemic began in mexico in 2009 and quickly spread worldwide. during the h1n1 pandemic, many patients were admitted to the winthrop-university hospital with influenza-like illnesses (ilis). many hospitalized adults had h1n1 pneumonia diagnosed by laboratory or clinical criteria. however, the laboratory diagnosis of h1n1 was problematic. the rapid influenza (quickvue a/b [quidel, san diego, ca]) test frequently showed false-negative results. reverse transcriptase-polym ...201120888645
domain within the c protein of human parainfluenza virus type 3 that regulates interferon signaling.human parainfluenza virus type 3 (hpiv3), one of the paramyxoviruses, uses its accessory c protein as an antagonist against interferon (ifn)-mediated host innate immunity. we have previously shown that the c protein significantly decreased the ifn-induced phosphorylation of signal transducer and activator of transcription (stat) 1 and the formation of gamma ifn activation factor (gaf) complex, thus abrogating the antiviral activity of the ifns against vesicular stomatitis virus (vsv) replication ...201021061916
progress in filovirus vaccine development: evaluating the potential for clinical use.marburg and ebola viruses cause severe hemorrhagic fever in humans and nonhuman primates. currently, there are no effective treatments and no licensed vaccines; although a number of vaccine platforms have proven successful in animal models. the ideal filovirus vaccine candidate should be able to provide rapid protection following a single immunization, have the potential to work postexposure and be cross-reactive or multivalent against all marburg virus strains and all relevant ebola virus speci ...201121162622
[a guinea pig model of parainfluenza virus type 3 infection-induced acute and postinfectious cough].to establish a guinea pig model of cough induced by human parainfluenza virus type 3 (piv3) infection, and to investigate the change of the cough reflex sensitivity (crs).201021211410
myocarditis caused by human parainfluenza virus in an immunocompetent child initially associated with 2009 influenza a (h1n1) virus.the association between respiratory viruses and myocarditis has hardly ever been described. we report a case of acute myocarditis in an immunocompetent child associated with the presence of parainfluenza virus type 3 infection, in a context of recent influenza illness, confirmed by molecular and serological studies.201121411596
premature activation of the paramyxovirus fusion protein before target cell attachment: corruption of the viral fusion machinery.paramyxoviruses, including the childhood pathogen human parainfluenza virus type 3 (hpiv3), enter host cells by fusion of the viral and target cell membranes. this fusion results from the concerted action of its two envelope glycoproteins, the hemagglutinin-neuraminidase (hn) and the fusion protein (f). the receptor-bound hn triggers f to undergo conformational changes that render it competent to mediate fusion of the viral and cellular membranes. we proposed that if the fusion process could be ...201121799008
a randomized, double-blind, placebo-controlled, phase 1/2a study of the safety and immunogenicity of a live, attenuated human parainfluenza virus type 3 vaccine in healthy infants.objective: to evaluate the safety, tolerability, immunogenicity, and viral shedding profiles of a recombinant, live, attenuated human parainfluenza virus type 3 (hpiv3) vaccine, rhpiv3cp45, in healthy hpiv3-seronegative infants 6 to <12 months of age. methods: in this double-blind, multicenter study, subjects were randomized 2:1 to receive a 10(5)tcid(50) dose of rhpiv3cp45 (n=20) or placebo (n=10) at enrollment and at 2 and 4 months after the first dose. blood for evaluation of antibody to hpiv ...201121782874
the cdna-derived investigational human parainfluenza virus type 3 vaccine rcp45 is well tolerated, infectious, and immunogenic in infants and young children.background:: human parainfluenza virus type 3 (hpiv3) is an important yet underappreciated cause of lower respiratory tract illness in children, and a licensed vaccine is not yet available. methods:: a live-attenuated investigational hpiv3 vaccine virus designated rcp45 was derived from cdna by using reverse genetics. rcp45 is genetically similar to the biologically derived cp45 vaccine virus and contains all of the known attenuating mutations of cp45, but has the advantage of a short, well-char ...201121829138
treatment of parainfluenza 3 infection with das181 in a patient after allogeneic stem cell transplantation.parainfluenza virus (piv) can cause significant morbidity after allogeneic stem cell transplantation (sct). we report the first use of inhaled das181 for piv in an allogeneic sct recipient. symptoms, oxygenation, and pulmonary function tests improved. nasopharyngeal samples showed a reduction in viral load. das181 should be systematically evaluated for severe piv infection.201121880586
analysis of nucleotides 13-96 of the human parainfluenza virus type 3 antigenomic promoter reveals positive- and negative-acting replication elements.during replication of human parainfluenza virus type 3 (hpiv3), the 96-nucleotide antigenomic promoter (agp) of hpiv3 directs the synthesis of genomic rna. previous work showed that nucleotides 1-12 were critical in promoting replication of an hpiv3 minireplicon, but nucleotides 13-96 were not investigated. in this study, the role of nucleotides 13-96 in agp function was analyzed by creating and assaying mutations in an hpiv3 minireplicon. a replication promoting element known as promoter elemen ...201121880340
host and viral traits predict zoonotic spillover from mammals.the majority of human emerging infectious diseases are zoonotic, with viruses that originate in wild mammals of particular concern (for example, hiv, ebola and sars). understanding patterns of viral diversity in wildlife and determinants of successful cross-species transmission, or spillover, are therefore key goals for pandemic surveillance programs. however, few analytical tools exist to identify which host species are likely to harbour the next human virus, or which viruses can cross species ...201728636590
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