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At least 1,117 records · Page 62Linked to original sources
PubMed2002

Impact of parainfluenza-3 virus infection on endothelin receptor density and function in guinea pig airways.

We examined the impact of parainfluenza-3 (P-3) respiratory tract viral infection on the density and function of endothelin (ET) receptor subtypes (ET(A) and ET(B)) in guinea pig tracheal smooth muscle. Total specific binding of [(125)I]ET-1 and the relative proportions of ET(A) and ET(B) binding sites for this ligand were assessed at day 0 (control) and at 2, 4, 8 and 16 days post-inoculation. At day 0, the proportions of ET(A) and ET(B) binding sites were 30% and 70% respectively. Total specific binding was significantly reduced at day 4 post-inoculation (32% reduction, n=8-12, P<0.05) and was largely due to a corresponding fall in ET(B) receptor density at this time point (38% reduction, n=8-12, P<0.05). The density of ET(A) receptors also fell significantly at day 8 post-inoculation (33% reduction, n=6-12, P<0.05). By day 16 post-inoculation, the densities of ET(A) and ET(B) receptors had recovered to control values. The ratio of ET(A):ET(B) receptor subtypes did not alter with P-3 infection. While P-3 infection reduced the density of tracheal smooth muscle ET(A) and ET(B) receptors, the contractile sensitivity and maximum response to carbachol and ET-1 was not altered in tissue from day 4 post-inoculation compared with the control. There seems to be a significant functional reserve for both receptor subtypes in this species that buffers the impact of P-3 infection on airway smooth muscle responsiveness to ET-1.

Analysis of Variance↗
PubMed2001

Pre-emptive oral ribavirin therapy of paramyxovirus infections after haematopoietic stem cell transplantation: a pilot study.

Infections with the paramyxoviruses, respiratory syncytial virus (RSV) and parainfluenza virus (PIV) can result in serious morbidity and mortality after haemopoietic stem cell transplant (HSCT). Once pneumonia develops, the outcome of these infections is often poor despite anti-viral therapy. Aerosolised ribavirin has been evaluated as pre-emptive therapy for post-transplant RSV infections with some success. Due to the financial and logistic burden involved with the use of aerosolised ribavirin, we explored the efficacy and toxicity of oral ribavirin for pre-emptive therapy of post-transplant RSV and PIV infections in a dose escalating schedule (15-60 mg/kg/day). Five episodes each of RSV and PIV were treated in seven patients. Five patients were receiving treatment for GVHD and two acquired the infection in the pre-engraftment period. All the episodes of RSV infection improved with oral ribavirin with dose escalation to 30-45 mg/kg in three of them. On the other hand, only two of the five PIV infections improved with oral ribavirin. Of the three non-responders, two infections were acquired in the pre-engraftment period with one death from PIV pneumonia. Reversible anaemia was the only side-effect noted in patients treated for over 2 weeks. Thus, the use of oral ribavirin was well tolerated in the post-transplant period with no untoward toxicities. There was a trend towards better response in RSV infections, which needs to be further explored in controlled studies.

Administration, Oral↗
PubMed1976

The assessment in sheep of an inactivated vaccine of parainfluenza 3 virus incorporating double stranded RNA (BRL 5907) as adjuvant.

The serological responses of conventionally reared sheep were compared after vaccination with inactivated parainfluenza 3 (PI3) virus incorporated in three different adjuvants. Inactivated PI3 virus with the double-stranded RNA, BRL 5907 in an oil emulsion was shown to stimulate higher serum antibody titres over the first 5 weeks after vaccination than virus with and without BCG emulsified in oil. The ability of this vaccine to protect specific pathogen-free lambs against challenge with PI3 virus was examined in a second experiment. In this experiment the vaccine stimulated virus neutralizing and haemagglutination inhibiting antibodies in the serum. After intranasal and intratracheal inoculation with PI3 virus at challenge, vaccinated lambs showed no clinical illness and virus isolation was confined, except in one lamb, to the first two days. In contrast, unvaccinated lambs developed respiratory disease and virus was isolated daily for 7 days after challenge.

Adjuvants, Immunologic↗
PubMed2005

Recombinant newcastle disease virus expressing a foreign viral antigen is attenuated and highly immunogenic in primates.

Paramyxoviruses such as human parainfluenza viruses that bear inserts encoding protective antigens of heterologous viruses can induce an effective immunity against the heterologous viruses in experimental animals. However, vectors based on common human pathogens would be expected to be restricted in replication in the adult human population due to high seroprevalence, an effect that would reduce vector immunogenicity. To address this issue, we evaluated Newcastle disease virus (NDV), an avian paramyxovirus that is serotypically distinct from common human pathogens, as a vaccine vector. Two strains were evaluated: the attenuated vaccine strain LaSota (NDV-LS) that replicates mostly in the chicken respiratory tract and the Beaudette C (NDV-BC) strain of intermediate virulence that produces mild systemic infection in chickens. A recombinant version of each virus was modified by the insertion, between the P and M genes, of a gene cassette encoding the human parainfluenza virus type 3 (HPIV3) hemagglutinin-neuraminidase (HN) protein, a test antigen with considerable historic data. The recombinant viruses were administered to African green monkeys (NDV-BC and NDV-LS) and rhesus monkeys (NDV-BC only) by combined intranasal and intratracheal routes at a dose of 10(6.5) PFU per site, with a second equivalent dose administered 28 days later. Little or no virus shedding was detected in nose-throat swabs or tracheal lavages following immunization with either strain. In a separate experiment, direct examination of lung tissue confirmed a highly attenuated, restricted pattern of replication by parental NDV-BC. The serum antibody response to the foreign HN protein induced by the first immunization with either NDV vector was somewhat less than that observed following a wild-type HPIV3 infection; however, the titer following the second dose exceeded that observed with HPIV3 infection, even though HPIV3 replicates much more efficiently than NDV in these animals. NDV appears to be a promising vector for the development of vaccines for humans; one application would be in controlling localized outbreaks of emerging pathogens.

Administration, Intranasal↗
PubMed1984

Resolution of two surface glycoproteins from human parainfluenza-3 virus by crossed immunoelectrophoresis.

The technique of two-dimensional crossed immunoelectrophoresis (CIE) was used to resolve two glycoproteins from purified human parainfluenza type 3 virus. Virus preparations were extracted with Triton X-100 and fractionated by centrifugation in a Beckman airfuge. Two immunoprecipitates were detected by CIE in the supernatant fractions, but were not found in the pellets from extracted virus. Viral glycoproteins labeled with [35S]methionine were isolated by affinity chromatography on concanavalin A (Con A) agarose columns, resolved by CIE and detected by autoradiography. Resolution of two glycoprotein peaks from as little as 4.5 micrograms of protein from extracted virus is consistent with results from polyacrylamide gel patterns showing two unique glycoproteins with molecular weights of 48 kd and 65 kd.

Chromatography, Affinity↗
PubMed1993

Acute lower respiratory illnesses during the first three years of life: potential roles for various etiologic agents. The Group Health Medical Associates.

Lower respiratory tract illnesses (LRIs) occurring during the first 3 years of life among children enrolled in the Tucson Children's Respiratory Study have been studied for evidence of viral, mycoplasmal and Chlamydia trachomatis infections. This report examines those from whom adequate acute and convalescent sera were available at the time of the LRI. Two groups were compared: those in whom culture and/or antigen detection yielded an etiologic agent (N = 110); and those who did not (culture negative, N = 124). Seroconversions (> or = 4-fold titer rise) to respiratory syncytial virus; influenza virus types A and B; parainfluenza virus types 1, 2 and 3; or adenovirus were found in only 0 to 5% of the culture negative group. No significant differences between groups with regard to frequencies of seroconversion to influenza type C, parainfluenza virus type 4, human coronaviruses 229E and OC43 or cytomegalovirus were detected, which suggests that these agents may not be frequent primary causes of LRIs among otherwise healthy children. Significant differences in seroconversions to Epstein-Barr virus were detected, suggesting that Epstein-Barr virus may contribute to LRI morbidity; however, its exact role remains to be defined.

Acute Disease↗
PubMed1991

Changes in lung mechanics and histamine responsiveness after sequential canine adenovirus 2 and canine parainfluenza 2 virus infection in beagle puppies.

We determined the effects of an immediately antecedent viral lower respiratory tract infection (LRI) on the severity of clinical illness, changes in lung function and airway histamine responsiveness produced by a subsequent LRI in 9-12 week old beagle puppies inoculated with canine adenovirus 2, followed in 2 weeks by inoculation with canine parainfluenza 2 virus (CAV2-CP12, n = 7). We compared their acute responses to puppies infected with CP12 alone (n = 5), CAV2 alone (n = 7), and no infection (control, n = 6). Puppies inoculated with either virus alone developed a LRI 3 to 6 days after inoculation which resolved by 12-14 days after inoculation. However, the illness was more severe in the CAV2 group. In the CAV2-CP12 group, CP12 infection following CAV2 infection resulted in a clinical illness nearly comparable to that observed with CAV2 alone. Whereas in control and CP12 puppies, lung resistance (RL) decreased and dynamic lung compliance (Cdyn) increased during the study due to normal growth, RL increased and Cdyn remained unchanged in the CAV2 group. In contrast, RL did not change and Cdyn increased in the CAV2-CP12 group. Airway histamine responsiveness in the CAV2-CP12 group increased during infection with CP12 and was similar to that observed with CAV2 alone. In contrast, infection with CP12 alone produced a small, but non-significant increase in histamine responsiveness. The duration of the increase in histamine responsiveness was not prolonged in the CAV2-CP12 group in comparison to CP12 or CAV2 alone. However, the length of clinical illness was extended in the CAV2-CP12 group in comparison to the other infected groups. These data suggest that an immediately antecedent viral LRI can potentiate the clinical and physiologic effects of a subsequent viral LRI.

Adenoviridae Infections↗
PubMed1974

A seven-year study of WHO virus laboratory reports on respiratory viruses.

In 1963 the World Health Organization established a system for the collection and distribution of information on viruses. By 1973 laboratories in 45 countries were participating in this scheme. The present study is an analysis of the reports on adenovirus, influenza viruses A, B, and C, parainfluenza virus, respiratory syncytial (RS) virus, rhinovirus, and Mycoplasma pneumoniae during 1967-73. In the northern hemisphere, from which over 95% of the reports were received, a clear pattern of the seasonal incidence of different respiratory tract infections emerged. Over 70% of the total number of reported adenovirus infections, over 80% of the parainfluenza virus infections, and over 90% of the RS virus infections were in children. M. pneumoniae infections were most frequently reported in adults. Influenza A virus infection was predominant in the adult population, with a high proportion in those aged 60 years and over. Influenza B infections were reported equally in adults and children, but over one third were in children of school age. The proportion of lower respiratory infections to total respiratory infections varied from one virus to another, and ranged from less than half for adenovirus to over four fifths for mycoplasma infections. Nonlocalizing fever was usually the second principal clinical condition reported in association with respiratory viruses.

Adenoviridae Infections↗
PubMed1975

The nasal secretion and serum antibody response of lambs following vaccination and aerosol challenge with parainfluenza 3 virus.

The nasal and serum neutralising antibody responses of lambs was compared following vaccination with live or inactivated parainfluenza 3 (PI 3) virus by either intramuscular (IM) or intranasal (IN) routes. Nasal antibody was only detected following inoculation of live virus IN or inactivated virus in Freund's complete adjuvant (FCA) IM. Immunity to aerosol challenge, as assessed by viral shedding from the nose, was conferred by (1) live virus administered by either route, (2) two IM inoculations of inactivated virus in FCA, and (3) one IM injection of inactivated virus in FCA followed by IN instillation of inactivated virus.

Administration, Intranasal↗
PubMed2000

Paramyxoviridae use distinct virus-specific mechanisms to circumvent the interferon response.

STAT1 and STAT2 are cellular transcription factors involved in interferon (IFN) signaling and are thus critical for the IFN-induced antiviral state. We have previously shown that the paramyxovirus Simian Virus 5 (SV5) blocks both type I and type II interferon (IFN) signaling by targeting STAT1 for proteasome-mediated degradation. To determine whether this is a feature common to all Paramyxoviridae, we examined the abilities of SV5, Sendai virus (SeV), human respiratory syncytial virus (RSV), and human parainfluenza viruses types 2 and 3 (hPIV2 and hPIV3, respectively) to block interferon signaling. The results showed that in reporter assays SV5, SeV, and hPIV3 blocked both type I and type II IFN-signaling; hPIV2 blocked type I but not type II IFN-signaling; and RSV failed to block either type I or type II IFN-signaling. In agreement with these results, SV5 and SeV inhibited the formation of the ISGF3 and GAF transcription complexes (essential for type I and type II signaling, respectively). Surprisingly, although hPIV3 inhibited IFN-induction of the ISGF3 complex, GAF complexes were detected in hPIV3-infected cells. hPIV2 also blocked the formation of the ISGF3 complex but not the GAF complex, whereas RSV failed to block the induction of either complex. SV5 was the only virus that caused the degradation of STAT1. Indeed, in SeV- and hPIV3-infected cells STAT1 was phosphorylated on tyrosine 701 (Y701), a characteristic of IFN receptor activation. However, consistent with these viruses blocking IFN signaling downstream of receptor activation, there was a specific reduction in the levels of serine 727 (S727)-phosphorylated forms of STAT1alpha in SeV- and hPIV3-infected cells. In contrast both (Y701)- and (S727)-phosphorylated forms of STAT1 were detected in hPIV2-infected cells but there was a specific loss of STAT2. Both STAT1 (including Y701- and S727-phosphorylated forms) and STAT2 could readily be detected in RSV-infected cells. Despite not being able to block type I or type II IFN signaling, RSV was able to replicate in human cells that produce and respond to IFN, suggesting that RSV must have an alternative method(s) for circumventing the IFN response. These results demonstrate that, although interference with IFN signaling is a common strategy among Paramyxovirinae, distinct virus-specific mechanisms are used to achieve this end.

Antiviral Agents↗
PubMed1978

Parainfluenza-3 virus exposure of beef heifers prior to natural breeding.

Ninety-six Hereford heifers (approximately 7 months of age) were randomly divided into 2 equal groups and housed 1.6 km apart (with 2 replications in time, 1 year apart). At 15 months of age, 1 group/replicate was inoculated with parainfluenza-3 virus, and the other group was given virus-free spent culture medium. Twenty-four hours later, 2 virgin bulls (2 years old) were placed with each group (24 cows) for natural breeding. Viral inoculation caused a twofold increase in parainfluenza-3 titer and a 0.3 C body temperature increase. There was no effect recognized from the virus on natural breeding efficiency.

Animals↗
PubMed1994

Correlation of proteolytic cleavage of F protein precursors in paramyxoviruses with expression of the fur, PACE4 and PC6 genes in mammalian cells.

The fusion (F) protein precursor of virulent Newcastle disease virus (NDV) strains and human parainfluenza virus type 3 (HPIV3) has a multibasic amino acid sequence at the cleavage site, and intracellular cleavage activation occurs in a variety of cells. The host protease responsible for the cleavage has been proposed to be a subtilisin-like protease (subtilase) such as furin (the product of the fur gene). We found that the lymphocyte cell lines MOLT-4, Ramos and Daudi, in addition to NALM6, lacked the ability to fully cleave the F protein precursor of virulent NDV. In contrast, MT4 as well as the non-lymphocyte cell lines HeLa and Hep2 cleaved the F protein precursor efficiently. To investigate the role of subtilases in proteolytic processing, we examined the gene expression of candidate subtilases, furin, PACE4 and PC6 in these cleavage-competent and -incompetent cells. Considerable expression of the fur gene was observed in the cleavage-competent cells, but little or no expression was detected in the cleavage-incompetent cells. PACE4 and PC6 gene expression was observed in some of the cleavage-competent cells but not in the cleavage-incompetent cells. These results suggest that furin is the protease responsible for cleavage activation of the F protein of virulent NDV strains in cultured mammalian cells and the possibility is raised that PACE4 and PC6 also participate in processing in some of the cells. On the other hand, the HPIV3 F protein was cleaved efficiently in lymphocyte cells deficient in subtilases, suggesting that an unknown protease other than furin, PACE4 or PC6 may be involved in the processing.

Amino Acid Sequence↗
PubMed1996

Functional interaction of paramyxovirus glycoproteins: identification of a domain in Sendai virus HN which promotes cell fusion.

The cell fusion activity of most paramyxoviruses requires coexpression of a fusion protein (F) and a hemagglutinin-neuraminidase protein (HN) which are derived from the same virus type. To define the domain of the HN protein which interacts with the F protein in a type-specific manner a series of chimeric HN proteins between two different paramyxoviruses, Sendai virus (SN) and human parainfluenza virus type 3 (PI3), was constructed and coexpressed with the SN-F protein by using the vaccinia virus T7 RNA polymerase transient-expression system. Quantitative assays were used to evaluate cell surface expression as well as fusion-promoting activities of the chimeric HN molecules. A chimeric HN protein [SN(140)] containing 140 N-terminal amino acids derived from SN-HN and the remainder (432 amino acids) derived from PI3-HN was found to promote cell fusion with the SN-F protein. In contrast, a second chimeric HN with 137 amino acids from SN-HN at the N terminus could not promote fusion with SN-F, even though the protein was expressed on the cell surface. A construct in which the PI3-HN cytoplasmic tail and transmembrane domain were substituted for those of SN in the SN(140) chimera still maintained the ability to promote cell fusion. These results indicate that a region including only 82 amino acids in the extracellular domain, adjacent to the transmembrane domain of the SN-HN protein, is important for interaction with the SN-F protein and promotion of cell fusion.

Animals↗
PubMed1983

Epizootic of parainfluenza-3 virus infection in gibbons.

A laboratory-housed breeding colony of white-handed gibbons (Hylobates lar) experienced an epizootic of upper respiratory tract disease characterized by lethargy, anorexia, coughing, and serous rhinorrhea. Signs were more severe in adults than in offspring, and all animals recovered without complications. Base-line, acute, and convalescent sera from the most severely affected gibbons were tested for antibodies against a wide spectrum of infectious agents. For personnel known to have had contact with the gibbons, testing for the same agents was done on base-line sera and sera obtained at the same time as the acute and convalescent sera were obtained from the gibbons. Rising titers against parainfluenza-3 virus were detected in 6 of 7 gibbons tested. An increase in titer was not seen in the sera of personnel.

Animals↗
PubMed1981

Antibody response of calves after intranasal inoculation with parainfluenza-3 virus and resistance of inoculated calves to experimental homologous viral infection.

The immunologic response of colostrum-deprived calves to parainfluenza-3 (PI-3) virus given by intranasal inoculation was studied. Inoculation of calves with 3.2 x 10(6) median cell culture infective doses (CCID50) of either virulent (SF-4) virus or a modified strain of PI-3 virus, or with 2.0 x 10(8) CCID50 of SF-4 virus, stimulated development of both serum antibody and nasal secretion (NS) antibody. However, NA antibody decreased in all calves between the 16th and 42nd postinoculation days and was present only at low or moderately low concentrations on the 126th day, when the immunity of the calves was challenged. Generally, calves that were inoculated with 3.2 x 10(6) CCID50 of SF-4 virus developed slightly higher concentrations of serum and NS antibodies than did calves inoculated with modified virus. Calves that were inoculated with 2.0 x 10(8) or 3.2 x 10(6) CCID 50 of SF-4 virus developed comparable concentrations of serum antibody, but large doses of SF-4 virus were less effective than smaller doses of the same virus in stimulating the development of NS antibody. Reinoculation of 3 calves with modified PI-3 virus resulted in a demonstrable increase in serum antibody in 2 calves and an increase and subsequent decrease in NS antibody in all calves. Challenge exposure of inoculated calves to aerosols of SF-4 virus failed to cause clinical signs of disease, and the challenge virus was not isolated from the nasal passages.

Animals↗
PubMed1971

Microtiter tests for detecting antibody in bovine serum to parainfluenza 3 virus, infectious bovine rhinotracheitis virus, and bovine virus diarrhea virus.

Microneutralization tests for detection of antibody in bovine serum to three bovine viruses are described. The Madin-Darby bovine kidney cell line was used with parainfluenza 3 virus (PI 3), whereas serially cultivated bovine embryonic kidney cells were used for infectious bovine rhinotracheitis virus and bovine virus diarrhea virus. Comparison of micro-hemagglutination-inhibition (HI) with micro-serum-neutralization (SN) tests for PI 3 showed the SN test to be more sensitive, more specific, and therefore more useful than the HI test for detecting antibody. Although the effect of trypsin-periodate treatment of serum was to reduce the HI titer of numerous sera by a twofold dilution, sufficient evidence could not be found to indicate that nonspecific HI inhibitors to PI 3 are present in bovine sera.

Animals↗