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PubMed1981

Antiviral compounds. XVII - Synthesis and in vitro antiviral activity of 1-substituted 2-chloro- and 2-methoxyindole-3-carboxaldehyde thiosemicarbazones.

A series of indole-3-carboxaldehyde thiosemicarbazones with substituent variations at the 1 and 2 positions were prepared and evaluated for in vitro antiviral activity against vaccinia virus strain IHD and parainfluenza virus type 3, HA-I/CR-8 strain. The inhibitory activity of most compounds was restricted to the vaccinia virus, only compounds (III e) and (III f) being effective against both viruses. Structure-activity relationship are discussed.

Antiviral Agents↗
PubMed1999

Isotype- and subclass-specific responses to infection and reinfection with parainfluenza-3 virus: comparison of the diagnostic potential of ELISAs detecting seroconversion and specific IgM and IgA.

Isotype- and subclass-specific indirect enzyme-linked immunosorbent assays were developed to detect parainfluenza-3 virus-specific IgG1, IgG2, IgM, and IgA responses. Sera were treated with protein G-agarose prior to testing for specific IgM and IgA to eliminate the possibility of false-positive results due to IgM-rheumatoid factor and to remove interisotypic competition due to specific IgG. IgM and IgA absorbance values were expressed as a percentage of the absorbance values of positive reference sera included on each plate (S/P%), and respective positive/negative threshold values of 15.0% and 28.0% were determined. The mean interval between experimental infection of 3 calves and initial detection of specific IgG1 and IgG2 responses was 8.0 and 9.3 days respectively, rising rapidly to an initial plateau 13.7 and 11.0 days postinfection (dpi). Reinfection of these calves at 30 dpi resulted in further rapid increases, with higher plateau values reached 13.0 (IgG1) and 13.7 (IgG2) days later. The mean interval between infection and the first positive IgM and IgA responses was 6.7 and 12.3 days, respectively. IgM S/P% values peaked at 13.0 dpi, with all 3 calves showing a secondary anamnestic response to reinfection, peaking 4.7 days later. The IgA response to initial infection was weak, with only 2 calves showing an obvious peak response at 15.0 dpi. A strong anamnestic IgA response to reinfection occurred in 2 calves, with a peak response 9.5 days later. Apparent biphasic and triphasic IgM and IgA responses were evident in some calves. Acute and convalescent serum samples from 80 calves involved in 17 outbreaks of respiratory disease were tested for specific IgM and IgA. Positive IgM results were detected in 15 outbreaks, with 71 sera from 44 calves testing positive. Although IgA-positive results were detected in the same 15 outbreaks, only 42 sera from 31 calves were positive. In a previous study, seroconversion was detected in 21 of these calves from 10 outbreaks. Thus the diagnostic potential of the assays was in the order IgM > IgA > seroconversion. The correlations between IgM and IgA, IgM and seroconversion, and IgA and seroconversion results for each calf were 73.8%, 58.8% and 62.5%, respectively.

Animals↗
PubMed2005

Respiratory syncytial virus and other respiratory viruses during the first 3 months of life promote a local TH2-like response.

BACKGROUND: Respiratory syncytial virus (RSV) infections during infancy are considered to be a risk factor for developing asthma and possibly allergic sensitization. OBJECTIVE: The aim of this study was to investigate the cytokines, chemokines, and eosinophil cationic protein in the nasopharyngeal secretions of infants < or = 7 months of age with RSV infections or other respiratory viral infections and healthy infants as controls. Groups were also analyzed according to age, < or = 3 months and >3 months, and the levels were compared within and between groups. RESULTS: Thirty-nine infants with RSV, 9 with influenza or parainfluenza virus infections and 50 controls with no history of infections, were enrolled in the study. The RSV-infected infants had significantly higher levels of IL-4; macrophage inflammatory protein 1beta, a chemoattractant for T cells; and eosinophil cationic protein in nasopharyngeal secretions compared with the control group. The levels of the TH2 cytokine IL-4 were significantly higher in RSV-infected infants < or = months of age compared with RSV-infected infants >3 months of age. In infants < or = 3 months of age, infections with influenza or parainfluenza virus caused TH2-like responses similar to those produced by RSV. CONCLUSION: Infections with RSV as well as with influenza and parainfluenza virus during early infancy preferentially promote a TH2-like response in the nose with local production of IL-4, IL-5, and macrophage inflammatory protein 1beta and infiltration and activation of eosinophils.

Age Factors↗
PubMed2002

Substance P receptor expression on lymphocytes is associated with the immune response to respiratory syncytial virus infection.

The kinetics and magnitude of SP receptor expression was determined for bronchoalveolar leukocyte cell subsets from BALB/c mice in the primary immune response to respiratory syncytial virus (RSV) and human parainfluenza virus-3 (PIV3) infection, and in the secondary immune response to RSV and PIV3 challenge. In both the primary and secondary responses to infection, expression of substance P (SP) receptors was markedly increased by infection, especially for T lymphocytes, compared to B220+, CD11b+ and CD14+ cells. CD4+ T lymphocytes predominantly expressed SP receptors in the secondary response. These results suggest that SP receptor expression may be important in the development of primary and secondary immune responses to respiratory virus infections.

Animals↗
PubMed1978

[Substances having antiviral activity. IX. Synthesis and antiviral activity of 1-acyl-2-halo-3-formylindole thiosemicarbazones].

Some thiosemicarbazones of 1-acyl-2-chloro-3-formylindoles were synthesized and investigated for antiviral activity against vaccinia virus, HID stock and parainfluenza virus type 3 HA-I/CR-8 stock. Evidence of antiviral activity was found only against vaccinia virus, and was particular significant with the m-substituted 1-benzoyl-2-chloro-3-formylindoles. The first results of 2-substitution of chlorine by bromine in the indole skeleton, are reported.

Antiviral Agents↗
PubMed1990

Antibody responses of humans and nonhuman primates to individual antigenic sites of the hemagglutinin-neuraminidase and fusion glycoproteins after primary infection or reinfection with parainfluenza type 3 virus.

An unusual feature of human parainfluenza virus type 3 (PIV3) is ita ability to cause reinfection with high efficiency. The antibody responses of 45 humans and 9 rhesus monkeys to primary infection or subsequent reinfection with PIV3 were examined to identify deficiencies in host immunologic responses that might contribute to the ability of the virus to cause reinfection with high frequency. Antibody responses in serum were tested by using neutralization and hemagglutination inhibition (HI) assays and a monoclonal antibody blocking immunoassay able to detect antibodies to epitopes within six antigenic sites on the PIV3 hemagglutinin-neuraminidase (HN) glycoprotein and eight antigenic sites on the fusion (F) protein. Primary infection of seronegative infants or children with PIV3 stimulated strong and rather uniform HI and neutralizing antibody responses. More than 90% of the individuals developed antibodies to four of the six HN antigenic sites (including three of the four neutralization sites), but the responses to F antigenic sites were of lesser magnitude and varied considerably from person to person. Young infants who possessed maternally derived antibodies in their sera developed lower levels and less frequent HI, neutralizing, and antigenic site-specific responses to the HN and F glycoproteins than did seronegative infants and children. In contrast, children reinfected with PIV3 developed even higher HI and neutralizing antibody responses than those observed during primary infection. Reinfection broadened the HN and F antigenic site-specific responses, but the latter remained relatively restricted. Adults possessed lower levels of HI, neutralizing, and antigenic site-specific antibodies in their sera than did children who had been reinfected, suggesting that these antibodies decay with time. Rhesus monkeys developed more vigorous primary and secondary antibody responses than did humans, but even in these highly responsive animals, response to the F glycoprotein was relatively restricted following primary infection. Bovine PIV3 induced a broader response to human PIV3 in monkeys than was anticipated on the basis of their known relatedness as defined by using monoclonal antibodies to human PIV3. These observations suggest that the restricted antibody responses to multiple antigenic sites on the F glycoprotein in young seronegative infants and children and the decreased responses to both the F and HN glycoproteins in young infants and children with maternally derived antibodies may play a role in the susceptibility of human infants and young children to reinfection with PIV3.

Adult↗
PubMed2006

A single intranasal inoculation with a paramyxovirus-vectored vaccine protects guinea pigs against a lethal-dose Ebola virus challenge.

To determine whether intranasal inoculation with a paramyxovirus-vectored vaccine can induce protective immunity against Ebola virus (EV), recombinant human parainfluenza virus type 3 (HPIV3) was modified to express either the EV structural glycoprotein (GP) by itself (HPIV3/EboGP) or together with the EV nucleoprotein (NP) (HPIV3/EboGP-NP). Expression of EV GP by these recombinant viruses resulted in its efficient incorporation into virus particles and increased cytopathic effect in Vero cells. HPIV3/EboGP was 100-fold more efficiently neutralized by antibodies to EV than by antibodies to HPIV3. Guinea pigs infected with a single intranasal inoculation of 10(5.3) PFU of HPIV3/EboGP or HPIV3/EboGP-NP showed no apparent signs of disease yet developed a strong humoral response specific to the EV proteins. When these animals were challenged with an intraperitoneal injection of 10(3) PFU of EV, there were no outward signs of disease, no viremia or detectable EV antigen in the blood, and no evidence of infection in the spleen, liver, and lungs. In contrast, all of the control animals died or developed severe EV disease following challenge. The highly effective immunity achieved with a single vaccine dose suggests that intranasal immunization with live vectored vaccines based on recombinant respiratory viruses may be an advantageous approach to inducing protective responses against severe systemic infections, such as those caused by hemorrhagic fever agents.

Administration, Intranasal↗
PubMed1994

Paramyxovirus mRNA editing leads to G deletions as well as insertions.

Paramyxoviruses are thought to edit their P gene mRNAs co-transcriptionally, by a mechanism in which the polymerase stutters and reads the same template base more than once. Sendai virus (SeV) and bovine parainfluenza virus type 3 (bPIV3) are closely related viruses, but SeV edits its P gene mRNA with the insertion of a single G residue (at approximately 50% frequency) within the sequence 5' A6G3, whereas bPIV3 inserts 1 to approximately 6 Gs at roughly equal frequency within the sequence 5' A6G4. When SeV synthetic mini-genomes containing either SeV or bPIV3 P gene editing cassettes are expressed from cDNA in cells which are also transfected with the SeV NP, P and L genes, the virus-specific editing patterns were reproduced. Since the bPIV3 editing pattern was reproduced in a system that is otherwise completely SeV, this suggests that all the information for the virus-specific editing patterns is due to the RNA sequence itself. Unexpectedly, the length of the template C run was found to be critical, even though it varies from 3 to 7 nucleotides in length in different viruses. Expanding this template C run first led to attenuation of the insertion phenotype, and then to deletions rather than insertions. A stuttering or slippage model to account for these events has been further refined to include a pressure which displaces the nascent strand in a given direction once it has disengaged from the template, and the similarities of this model to those which account for readthrough of cellular RNA polymerase transcription blocks are discussed.

Base Sequence↗
PubMed2001

[Analysis of etiology of influenza-like morbidity and monitoring influenza epidemic of 1998-1999 by laboratory diagnosis methods].

The etiological structure of influenza-like was analyzed in the population in cities and towns and in Russia as a whole in November 1998 to April 1999 by the findings of immunofluorescence and serological surveys of patients with acute respiratory viral infections (ARVI). By the results of both tests, the proportion of the incidence of influenza A (H3N2) was largest, the decreasing order in their significance was as follows: adenoviruses, type 3 parainfluenza virus, RSV, influenza B virus, influenza A(H1N1), types 2 and 1 parainfluenza virus. All influenza viruses A(H1N1) were isolated in Samara in February 1999. Three of them were similar to the reference strain A/Johannesburg/82/96 in antigenic properties, two strains appeared to be its drift variants. No A/Beijing/262/95 (H1N1)-like viruses recommended for incorporation as part of vaccines were detected. All influenza A(H3N2) viruses were drift variants of strain A/Sydney/05/97, and all influenza B viruses were similar to the reference strain B/Harbin/07/94 in antigenic structure.

Clinical Laboratory Techniques↗
PubMed1990

Sequence determination of the hemagglutinin-neuraminidase (HN) gene of human parainfluenza type 2 virus and the construction of a phylogenetic tree for HN proteins of all the paramyxoviruses that are infectious to humans.

The nucleotide sequence of the hemagglutinin-neuraminidase (HN) gene of human parainfluenza type 2 virus (PIV-2) was determined. The PIV-2 HN gene was 2112 nucleotides excluding poly(A) tail. There was a single large open reading frame in the mRNA which encoded a protein of 571 amino acids with a calculated molecular weight of 63,262. Analysis of the deduced amino acid sequence revealed that there were fourteen potential glycosylation sites and a major hydrophobic region near the N-terminus, which would anchor the protein in the viral membrane. Comparisons of the HN protein sequences of PIV-2 with those of Simian virus 5 (SV5), Sendai virus (SV, parainfluenza virus type 1), human parainfluenza virus type 3 (PIV-3), type 4 (PIV-4), bovine parainfluenza virus type 3 (BPIV-3), mumps virus (MuV), and Newcastle disease virus (NDV) showed definite amino acid sequence relatedness, indicating a common ancestor for these viruses. Furthermore, statistical analysis of the protein sequences suggested a possible evolutionary relatedness among the paramyxoviruses. This is the first time that a phylogenetic tree has been constructed for all the parainfluenza viruses and mumps virus which are infectious to humans. In addition, amino acid sequences involved in hemagglutinating and neuraminidase activities of paramyxovirus were discussed.

Amino Acid Sequence↗
PubMed1977

Maintenance of viability and comparison of identification methods for influenza and other respiratory viruses of humans.

A comparison of Hanks balanced salt solution, veal infusion broth (VIB), and charcoal viral transport medium for maintaining viability of type A influenza virus indicated approximately equal survival of virus on all three media at -70 and 4 degrees C, whereas at 25 degrees C virus survived best in VIB. VIB supplemented with bovine serum albumin was used as transport medium in a community-wide surveillance of febrile respiratory disease for influenza viruses. Unfrozen throat swab specimens were placed in VIB and stored at 4 degrees C for up to 5 days without effect on isolation frequencies of either type A or type B influenza virus or type 1 or type 3 parainfluenza virus. Comparison of indirect immunofluorescence with hemadsorption for detection of type A influenza virus in rhesus monkey kidney cultures revealed a requirement for at least five fluorescing cells to eliminate false positive indirect immunofluorescence tests and at least 3 days of incubation to eliminate false negative tests when compared with hemadsorption at later times. Detection frequencies for the two methods after 2 and 3 days of incubation were not significantly different.

Culture Media↗
PubMed1998

Viral aetiology and epidemiology of acute respiratory infections in hospitalized Saudi children.

A total of 1429 Saudi children of either sex and under 5 years of age who were admitted to King Khalid University Hospital, Riyadh during a three year period (April 1993-March 1996) with complaints suggestive of acute respiratory tract infections (ARTI) were investigated for viral aetiology of the infection. Viruses could be detected in 522 (37 per cent) cases with respiratory syncytial virus (RSV) the most commonly detected (79 per cent) followed by parainfluenza type 3 (8 per cent). Detection of influenza A, B and adenoviruses accounted for 6 per cent, 3 per cent and 2 per cent respectively. Except for parainfluenza virus type 3 the peak of activity of the respiratory viruses was during the winter months (October-February). Parainfluenza virus type 3 could be detected all year round but epidemics can occur in the hottest months of the year (June-August) when the temperature can exceed 40 degrees C. Association between clinical manifestation, type of causative agent, and age was evaluated in 137 infected Saudi children in the first year of the study (April 1993-March 1994). The majority of our cases presented with bronchiolitis (58 per cent) while only 26 per cent had bronchopneumonia. There was a significant association between bronchiolitis and lower age groups (0-6 months), with RSV as the major causative agent of bronchiolitis cases (88 per cent).

Acute Disease↗
PubMed1990

Immunological relationships of simian virus 41 (SV41) to other paramyxoviruses and serological evidence of SV41 infection in human populations.

Antigenic relationships of simian virus 41 (SV41) to other paramyxoviruses were examined by immunoprecipitation of isotope-labelled SV41-infected cell lysates with specific antisera. SV41 is closely related to the group comprising human parainfluenza virus 2 (HPIV-2), simian virus 5 (SV5), parainfluenza virus 4 and mumps virus. Slight cross-neutralization was detected between SV41, HPIV-2 and SV5. Anti-SV41 activities were detected in 21 of 1116 human serum specimens, indicating that a proportion of the human population is infected with SV41. The haemagglutinin-neuraminidase of SV41 was preferentially immunoprecipitated by anti-SV41 positive sera.

Animals↗
PubMed1977

Parainfluenza viral infections in children: correlation of shedding with clinical manifestations.

Children presenting with acute respiratory disease to a private group practice in the fall of 1975 were studied to: (1) evaluate the efficacy in a pediatric office of a simple technics of obtaining nasal washes for the diagnosis of parainfluenza virus infections and (2) to determine the quantities of virus shed in relation to clinical characteristics. The nasal wash technic proved feasible for an office or clinic. Parainfluenza virus type 1 was recovered from 26 (74%) of 35 children with croup and from 40 (56%) of the total 72 children presenting with any form of respiratory illness. Virus was recovered significantly more often from children with croup and from those of younger age. The mean quantity of virus in 26 nasal washes was 2.97 log10 TCID50/ml. The shedding of greater quantities was correlated with younger age and the more frequent occurrence of laryngitis, pharyngitis, and fever.

Acute Disease↗
PubMed2001

Cellular immunity and memory to respiratory virus infections.

Respiratory virus infections, such as those caused by influenza and parainfluenza viruses, are a major cause of morbidity and mortality worldwide. Current vaccines against these pathogens rely on the induction of humoral immune responses that target viral coat proteins. Although this type of immunity provides solid protection against homologous virus strains, it is ineffective against heterologous virus strains that express serologically distinct coat proteins. In contrast, cellular immune responses can target internal antigens that are shared between heterologous viral strains. This form of immunity, sometimes referred to as heterosubtypic immunity, can mediate a substantial degree of protection. Thus, vaccines that emphasize cellular immune responses would be a valuable complement to available humoral vaccines. However, we only have a rudimentary understanding of which T cell subsets mediate protective immunity, how T cell memory is established and maintained, how that memory is recalled in a secondary infection, and why cellular immunity wanes rapidly with time. Here we review the role of CD4+ and CD8+ T cells in the recall response to influenza and parainfluenza viruses. In particular we focus on the recent observation that substantial numbers of memory T cells are established in the lung tissues and discuss the potential role of these cells in mediating a recall response. A thorough understanding of the cellular immune response to infection in the lungs is essential for future vaccine development.

Animals↗
PubMed1995

Respiratory virus antibodies in adults of a Norwegian community: prevalences and risk factors.

BACKGROUND: The aims were to examine prevalences as well as demographic and environmental predictors of respiratory virus antibodies in serum. METHODS: In a cross-sectional study of 18-73 year old Norwegian adults a random stratified sample (n = 1512) was invited to attend an examination at an outpatient clinic. Seven respiratory virus antibodies were assessed by the complement fixation test. RESULTS: The attendance rate was 84%. The most frequent virus antibodies with titre of > or = 1:8 were influenza virus type A with a population standardized prevalence of 44%, adenovirus 25% and influenza virus type B 22%. The prevalences of antibodies against parainfluenza virus type 1, 2 and 3 increased with age. Smokers compared to non-smokers had an adjusted odds ratio (OR) of 1.7 (95% confidence interval [CI]: 1.3-2.4) for having one or more of the seven examined virus antibodies. The presence of one or more of the virus antibodies increased from summer to winter months (adjusted OR = 1.3 per month; 95% CI: 1.2-1.4) and it was higher in occupational dust or gas exposed smokers (adjusted OR = 2.0; 95% CI: 1.1-3.7) compared with unexposed smokers. CONCLUSIONS: Ageing, smoking, occupational dust or gas exposure as well as season of the year may thus be predictors for levels of respiratory virus antibodies in adults. These observations should be taken into account when comparing prevalences of virus antibodies in various communities as well as when examining the relationship between presence of virus antibodies and airway disease.

Adenoviridae↗
PubMed1979

Aerosol stability of bovine parainfluenza type 3 virus.

Aerosols of bovine parainfluenza type 3 virus were generated with a Devilbiss 40 nebulizer from Eagle's minimum essential medium and nasal secretion from a non-infected calf and stored in a rotating drum at temperatures of 6 degrees C or 32 degrees C and relative humidities of 30% or 90%. The aerosols were sampled at seven minutes, one, two and three hours after the start of generation with an all glass impinger (AGI-30) and titrated for infectivity in cell cultures. Physical decay was determined by a rhodamine tracer technique. Media, temperature or relative humidity had little effect on the survival of parainfluenza type 3 virus during spraying (zero to seven minutes). During aging of aerosols at 32 degrees C and 30% relative humidity, parainfluenza type 3 virus was less stable in Eagle's minimum essential medium than in nasal secretion from a noninfected calf, but at 6 degrees C and 30% relative humidity, the virus was more stable in Eagle's minimum essential medium. At 32 degrees C, the virus was less stable during aging at 90% relative humidity than at 30% relative humidity. The virus was consistently more stable during aging of aerosols at 6 degrees C than at 32 degrees C.

Aerosols↗