Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “parainfluenza virus”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,567 records · Page 87Linked to original sources

The value of polymerase chain reaction for the diagnosis of viral respiratory tract infections in lung transplant recipients.

BACKGROUND: Respiratory viruses cause severe infections in lung transplant recipients, which require rapid and accurate diagnosis for appropriate management. OBJECTIVES: To evaluate the added benefit of a multiplex PCR for respiratory viruses (influenza [FLU] A and B, respiratory syncytial virus [RSV] A and B and parainfluenza virus [PIV] 1, 2, and 3) complementing rapid respiratory viral culture (RRV) and FLU-A antigen detection (EIA) in this transplant population. RESULTS: Over 6 months, 116 nasal washes and bronchoalveolar lavages, obtained from 72 lung transplant recipients with symptoms of upper or lower respiratory tract infections, were tested in real time by RRV and FLU-A EIA, and batched frozen by PCR. One or more methods recognized a respiratory virus in 31 (27%) specimens, including 15 FLU-A, nine RSV and seven PIV. PCR identified 26 of 31 positive samples demonstrating a sensitivity of 84%, higher than RRV (67%) or EIA (54%). PCR, RRV and EIA detected 60, 80 and 54%, respectively, FLU-A samples. PCR and RRV were equivalent for RSV-A, PIV-2 and 3, but PCR found a significantly higher number of RSV-B and PIV-1. CONCLUSIONS: These data indicate that routine use of PCR will enhance the number and speed with which viral respiratory tract infections are diagnosed in lung transplant recipients.

Adult↗

Pityriasis rosea--evidence for and against an infectious aetiology.

Pityriasis rosea, first named as such in 1860, probably holds the longest record for an exanthem suspected to be associated with an infection but for which an exact cause has not been found. The distinctly programmed clinical course, the lack of recurrence for most patients, and the presence of temporal case clustering provide the strongest evidence to support an infectious aetiology. Further support comes from seasonal variation and the association with respiratory tract infections, the unfavourable social and economic background of cases, and a history in some cases of contact with patients with pityriasis rosea. The apparent therapeutic efficacy of several treatment modalities does not provide strong evidence for or against an infectious aetiology. The roles of human herpesvirus 7 and to a lesser extent human herpesvirus 6 remain controversial. There exists reasonable evidence that pityriasis rosea is not associated with cytomegalovirus, Epstein-Barr virus, parvovirus B19, picornavirus, influenza and parainfluenza viruses, Legionella spp., Mycoplasma spp. and Chlamydia spp. infections. Evidence is also unsubstantiated as yet for alternative aetiological hypotheses such as autoimmunity, atopy, and genetic predisposition.

Bacterial Infections↗

Antiviral activity of N-benzoylphenylisoserinates of Lactarius sesquiterpenoid alcohols in vitro.

Cytotoxic, antiviral, antibacterial and antifungal properties of a new, originally synthesised group of compounds: the N-benzoylphenylisoserinates of sesquiterpenoid alcohols - derivatives of taxol and various sesquiterpenes of Lactarius origin were evaluated in vitro. Among 16 compounds tested, 6 decreased HSV-1 titres. Selectivity indices ranged from 13.9 to 31.7. No activity against RNA viruses (parainfluenza 3, Coxsackie B3, vesicular stomatitis virus, and encephalomyocarditis virus), bacteria: Escherichia coli, Proteus mirabilis, Staphylococcus aureus, Enterococcus faecium and Bacteroides fragilis and fungal strain of Candida albicans was detected.

Agaricales↗

Etiology and antimicrobial therapy of acute maxillary sinusitis.

Eighty-one adults with symptoms of acute sinusitis were studied by direct needle puncture and aspiration of the maxillary sinus (105 sinuses). Fifty-nine bacterial strains were isolated in titers of greater than or equal to 10(4) colony-forming units/ml; Streptococcus pneumoniae and Haemophilus influenzae accounted for 64% of the isolates. Other bacteria recovered included anaerobes (12%), Neisseria species (8.5%). Streptococcus pyogenes (3%), alpha-hemolytic Streptococcus (3%), non-group A beta-hemolytic Streptococcus (3%), Staphylococcus aureus (2%), Pseudomonas aeruginosa (2%), and Escherichia coli (2%). Viruses were isolated from 11 sinuses; these isolates included rhinovirus (six), influenza A (H3N2) virus (three), and two types of parainfluenza virus (one each). The efficacy of therapy with orally administered ampicillin, amoxicillin, or trimethoprim-sulfamethoxazole was evaluated by a repeat sinus puncture and culture. Clinical and bacteriologic responses to all three regimens were good.

Adult↗

The pediatrician's role in influenza control.

Influenza is the most important of acute respiratory illnesses that cause persons to seek medical care. For infants some other viruses such as respiratory syncytial and parainfluenza viruses share in the assault but influenza is the only respiratory virus for which we have tools for prevention. We need to use these tools effectively to build a wall of protection around vulnerable patients. The fact that influenza vaccine does not have the same efficacy as other pediatric vaccines should not discourage its use but should challenge us to implement fully the current recommendations. Not only is influenza a slippery, changeable virus but also the pathogenesis of the infection and the host response are different. Influenza virus invades and destroys the respiratory epithelium and a viremic phase is not essential to this destruction. Therefore the virus is sheltered from many of the host immune and protective mechanisms that can be stimulated by natural infection or vaccines. Furthermore immunity to influenza tends to wane even after natural infection. Thus the challenge is to extend the utilization of the available vaccine and the antiviral to decrease the unrelenting serious morbidity associated with influenza. The hope is that better vaccines and antivirals will soon be available to aid in the battle. The cold recombinant vaccine, a live attenuated virus developed by Massaab, has potential for use in children. Rimantadine, an analogue of amantadine, has fewer side reactions and has been shown to be effective in children. Ribavirin, recently licensed for treatment of respiratory syncytial virus disease, is also effective for treatment of both influenza A and B viruses.

Amantadine↗

National disease burden of respiratory viruses detected in children by polymerase chain reaction.

BACKGROUND: The epidemiology of community-acquired respiratory viruses at the Children's Hospital of Wisconsin between 1996 and 1998 was examined with molecular [multiplex (M) PCR] and standard virologic methods. METHODS AND RESULTS: A total of 3325 patients with lower respiratory infection (LRI) [bronchiolitis (42%), pneumonia (38%) and croup (12%)] were identified. It is estimated that 545,000 LRI hospitalizations occur each year in the United States in children younger than 18 years old (viral, 428,000; pneumonia, 221,000; bronchiolitis, 222,000; croup, 65,000), including a continued increase in bronchiolitis hospitalizations (47.8/1000; <1 year). The most common viruses detected each year in hospitalized children included respiratory syncytial virus (A and B; 117,000), parainfluenza virus (PIV-1 and -2, 48 000; PIV-3, 18,000) and influenza (A and B, 39,000). With multiplex reverse transcription polymerase chain reaction (MPCR), different patient populations demonstrated different LRI epidemiology in relation to specific syndromes and viral causes. At least 21% of LRI hospitalizations were in children with significant medical problems.PIVs were detected much more frequently in immunocompromised children than in previously healthy children (33% vs. 16%). Similarly 15% of respiratory syncytial virus was detected between May and October, mostly in immunocompromised children. Influenza caused 19% of bronchiolitis in previously healthy children, and no virus could be reliably predicted based on clinical presentation, including wheezing. Of children hospitalized for LRI, 40% tested positive for the seven most common respiratory viruses by MPCR. CONCLUSIONS: Work is under way to expand the number of viruses detected by MPCR and to determine whether newly discovered viruses, such as human metapneumovirus, contribute to the burden of pediatric LRI hospitalizations.

Adolescent↗

Prospective study of human metapneumovirus infection in children less than 3 years of age.

Most lower respiratory tract infections (LRTIs) in children under the age of 3 years are due to respiratory syncytial virus (RSV). Epidemiological, host, and viral factors eventually account for the severity of LRTIs, but they do not completely explain it. Human metapneumovirus (hMPV) was recently identified in children with LRTIs. In a population-based prospective multicenter study (the PRI.DE study, conducted in Germany over 2 years), we tested 3,369 nasopharyngeal secretions from children younger than 3 years of age with LRTIs for RSV A and B, influenza viruses (IVs) A and B, and parainfluenza viruses (PIVs) 1 to 3. Of the children requiring intensive care (n = 85), 18% had hMPV infections, and 60% of these children were infected with hMPV in combination with RSV. We did not detect hMPV in a randomly selected subset of RSV-positive nasopharyngeal secretions (n = 120) from children not requiring intensive care support. hMPV was detected in <1% of virus-negative samples from patients without intensive care support (n = 620). Our data support the hypothesis that coinfections with RSV and hMPV are more severe than infections with either RSV or hMPV alone, at least in children younger than 3 years of age.

Child, Preschool↗

The versatility of paramyxovirus RNA polymerase stuttering.

Paramyxoviruses cotranscriptionally edit their P gene mRNAs by expanding the number of Gs of a conserved AnGn run. Different viruses insert different distributions of guanylates, e.g., Sendai virus inserts a single G, whereas parainfluenza virus type 3 inserts one to six Gs. The sequences conserved at the editing site, as well as the experimental evidence, suggest that the insertions occur by a stuttering process, i.e., by pseudotemplated transcription. The number of times the polymerase "stutters" at the editing site before continuing strictly templated elongation is directed by a cis-acting sequence found upstream of the insertions. We have examined the stuttering process during natural virus infections by constructing recombinant Sendai viruses with mutations in their cis-acting sequences. We found that the template stutter site is precisely determined (C1052) and that a relatively short region (approximately 6 nucleotides) just upstream of the AnGn run can modulate the overall frequency of mRNA editing as well as the distribution of the nucleotide insertions. The positions more proximal to the 5' AnGn run are the most important in this respect. We also provide evidence that the stability of the mRNA/template hybrid plays a determining role in the overall frequency and range of mRNA editing. When the template U run is extended all the way to the stutter site, adenylates rather than guanylates are added at the editing site and their distribution begins to resemble the polyadenylation associated with mRNA 3' end formation by the viral polymerase. Our data suggest how paramyxovirus mRNA editing and polyadenylation are related mechanistically and how editing sites may have evolved from poly(A)-termination sites or vice versa.

5' Untranslated Regions↗

Composition and assembly of STAT-targeting ubiquitin ligase complexes: paramyxovirus V protein carboxyl terminus is an oligomerization domain.

Transcription regulators STAT1 and STAT2 are key components of the interferon signaling system leading to innate antiviral immunity. The related STAT3 protein is a regulator of interleukin-6-type cytokine signals and can contribute to both cell growth and death important for cancer gene regulation and tumor survival. These three STAT proteins are targeted for proteasome-mediated degradation by RNA viruses in the Rubulavirus genus of the Paramyxoviridae. A single viral protein, the V protein, assembles STAT-specific ubiquitin ligase complexes from cellular components. Simian virus 5 (SV5) targets STAT1, human parainfluenza virus 2 targets STAT2, and mumps virus targets both STAT1 and STAT3. Analysis of the V-dependent degradation complex (VDC) composition and assembly revealed several features contributing to targeting specificity. SV5 and mumps V proteins require STAT2 to recruit the STAT1 target, yet mumps V protein binds STAT3 independent of STAT1 and STAT2. All Rubulavirus V proteins tested require cellular DDB1 to target STATs for degradation but differ in the use of Roc1, which is essential for mumps V STAT3 targeting. Protein interaction analysis reveals that paramyxovirus V proteins can homo- and heterooligomerize and that the conserved cysteine-rich zinc-binding C-terminal domain is necessary and sufficient for oligomerization. Purified SV5 V protein spontaneously assembles into spherical macromolecular particles, and similar particles constitute SV5 and mumps VDC preparations.

Carrier Proteins↗

Otitis media in Greenland. Studies on historical, epidemiological, microbiological, and immunological aspects.

This thesis describes the different aspects of otitis media (OM) in the population of Greenland viewed in a historical and modern clinical perspective. Chapter 1 outlines the addressed problems and aims while chapters 2 and 3 deal with historical studies and an evaluation of the present knowledge based on the literature. Physical anthropological studies, using skeletal samples of adult Eskimo crania from before and after the colonization of Greenland in 1721 and information about modern living Eskimos (Inuit), have shown that OM sequelae of the temporal bones were significantly less common in pre-colonization Eskimos and that the mean area size of the pneumatized cell system in the temporal bone was significantly larger in pre-colonization Eskimos. These findings indicated an increase in OM after the colonization most likely caused by the social, cultural, habitary, and dietary changes due to increased contact with the outside world. Historical reports after the colonization confirm a high prevalence of OM especially in children. Modern epidemiological studies from the 1960's to 1980's in the Arctic region of Alaska, Canada, and Greenland along with reports from visiting consultant otologists in Greenland almost uniformly mention prevalent OM problems in children as well as in adults. The aim was therefore to further describe the epidemiological pattern of the different OM disease entities (acute OM (AOM), chronic OM (COM), COM with suppuration (CSOM), secretory OM (SOM), and cholesteatoma) and investigate the potentially associated risk factors in especially Greenlandic children because these diseases are primarily established and problematical in childhood. Chapter 4 describes the definitions used in the thesis and chapter 5 describes the studies included. Section 5.1 describes a study of cholesteatoma in Greenlanders. The study revealed an almost similar incidence of hospital treated children with cholesteatoma (6.6 per 100,000) as seen in comparable studies from other parts of the world. Furthermore, childhood cholesteatomas were the most aggressive. The frequency of residuals or recurrences after otosurgical treatment was high with a trend for better results when using the extensive canal wall-down procedure. It could be concluded that these patients urgently need close follow-up for at least five years postoperatively, if not lifelong. Section 5.2 describes a hearing screening survey of 167 school children using school registration charts. A high prevalence of hearing loss (HL) was found. A total of 43% of the children had hearing thresholds exceeding 20 dB at one or more frequencies between 250-8000 Hz in one or both ears, and 19% had the same type of HL in the frequencies 500-2000 Hz. HL was significantly associated with episodes of OM. These findings were in accordance with reports from Alaska and Canada. It is therefore concluded that a hearing screening programme of school children is important and that OM seems to have an impact on hearing in school children in Greenland. In section 5.3 an epidemiological survey is described concerning the prevalence of the different OM disease entities. The survey was carried out in Nuuk and Sisimiut and involved 740 children aged 3, 4, 5, and 8 years. A total of 591 children participated and selection bias was not found when controlling for age, sex, and episodes of AOM. The survey revealed that 52% of children in Nuuk and 54% in Sisimiut had some kind of pathological affection of their middle ear. COM and CSOM were found in 9%, but more prevalent among children in Sisimiut (12%) than in Nuuk (7%). Middle ear effusion (MEE) diagnosed by tympanometry was found in 23% in Nuuk and 28% in Sisimiut while simple tubal dysfunction (STD) was found in 13% and 8%, respectively. MEE and STD were associated with young age. Sequelae of OM was apparent in 11% in both towns. When comparing the results with a 10-year-older, almost similar survey of 142 children, it was evident that the OM situation had not changed in the period between the studies. The survey underlines the need for increased focus on the different OM entities in Greenlandic children. Section 5.4 deals with microbiological aspects. The nasopharyngeal microflora and ear discharge microflora of potential pathogens were evaluated in 54 children with AOM and in 201 control children without AOM. Very high carriage rates expressed qualitatively and semiquantitatively of potentially pathogenio bacteria were found in the nasopharynx of children with AOM (98%) but also in that of the control children (91%) and even in children denoted as being very healthy (94%). However, the same bacterial species were cultured from the nasopharynx and ear discharge as in comparable studies world-wide. Only S. pneumoniae was carried significantly more often in the nasopharynx of AOM children compared with age matched control children. Chlamydiae, M. pneumoniae, adenovirus, respiratory syncytial virus, parainfluenza- type 1, 2, and 3 virus, and influenza- type A and B virus were not major pathogens. In contrast, entero- and rhinoviruses were detected significantly more frequent in nasopharyngeal specimens from AOM children (59%) compared with age matched controls (33%) and also in 29% of the examined ear discharge specimens. It is therefore concluded that the potentially pathogenic bacterial load is early and massive. This alone or in interplay with entero- and rhinovirus infection and occasionally with other viruses may play an important role in the high prevalence of OM among children in Greenland. Section 5.5 deals with an examination of potential risk factors for AOM, recurrent AOM (rAOM), and COM in the same 591 children as studied in section 5.3. Early age at first AOM episode was associated with rAOM episodes (> or = 5 episodes since birth). Thus, the relative risk of developing rAOM was eight times higher if the first episode of AOM occurred before 7 months of age than after 24 months of age. Furthermore, compared with studies elsewhere in the world, a high proportion (40%) of the children in this survey had their first AOM episode during their first year of life and 41% of these children developed rAOM. It was also found that children had an increased risk of AOM, rAOM, or COM when both parents were born in Greenland, when parents also have had OM, when living in very crowded households, and when having experienced a long period of exclusive breast feeding, or when recalling of breast feeding was not possible. Gender, type, and size of housing, insulation standard of housing, daycare, exposure to passive cigarette smoking, and dietary habits were not associated with AOM, rAOM, or COM in the surveyed children. It is concluded that early onset of AOM occurs frequently in Greenlandic children and that a high proportion of these children develop rAOM. The study confirms that AOM is a highly multifactorial disease determined by a number of genetic and environmental factors. Finally, section 5.6 is a hypothesis generating study attempting to explain the high prevalence of early episodes of AOM in community-based children in Nuuk. The hypothesis is based on a possible association between findings of mannose-binding lectin genotypes, early Epstein-Barr virus infections and episodes of AOM, rAOM, or nasopharyngeal colonization with potentially pathogenic bacteria. However, the study does not support any of this hypothesis. In chapter 6, future studies are suggested and chapter 7 presents concluding remarks.

Carrier Proteins↗

[The influence of winter 2002 in pediatric health: dissociation between environmental factors and respiratory syncytial viruses, in Santiago].

BACKGROUND: The increase in winter related health pediatric demand is associated with three factors: cold and rainy weather, air pollution and respiratory viral epidemics. During the winter of 2002 there was, successively, heavy rain, air pollution, cold weather and a respiratory syncytial virus (RSV) epidemic in Santiago. AIM: To study the influence of environmental factors and RSV epidemic on pediatric health care demand. PATIENTS AND METHODS: The number of hospital admissions and outpatient consultations for acute lower respiratory infections (ALRI) from April to October 2002 (Autumn to Spring in Chile), were registered in a public pediatric hospital of Santiago. A respiratory virus surveillance (RSV, adenovirus influenza and parainfluenza virus) was carried out among children admitted for ALRI. Climate conditions and air pollution (number of particles of more than 10 microns/mm3) values were provided by local environmental health services. RESULTS: As expected, a rise in winter hospital admissions and outpatient consultations was detected, that peaked in week 29. This rise coincided with the higher RSV detection week. There was heavy rain in weeks 22, 23 and 30, as well as cold weather in June-July (weeks 23, 24, 26, 27 and 30; mid Winter), that did not increase health care demand. Likewise, high air pollution, registered from weeks 24 to 26, did not increase health care demand. CONCLUSIONS: RSV epidemic is the principal factor associated to the increase in health burden during winter in Santiago.

Adolescent↗

Respiratory viruses and influenza-like illness: a survey in the area of Rome, winter 2004-2005.

Limited information is available on the viral aetiology of influenza-like illness (ILI) in Southern European countries. Hereby we report the main findings of a survey conducted in the area of Rome during the 2004-2005 winter season.ILI cases were defined as individuals with fever >37.5 degrees C and at least one constitutional symptom and one respiratory symptom, recruited during the survey period. Influenza and other respiratory viruses were identified using polymerase chain reaction (PCR) on throat swabs. Basic individual information was collected through a standard form. Of 173 ILI cases enrolled, 74 tested positive for one virus, and two tested positive for two viruses. Overall, 33.5% of the cases were positive for influenza viruses, 5.2% for adenoviruses, 3.5% for parainfluenza viruses, 1.7% for coronaviruses, and 1.2% for the respiratory syncitial virus. The proportion of influenza virus detection was higher in the 'high influenza activity' period. The distribution of viral agents varied across age groups, influenza viruses being more likely to be detected in younger patients. Viral pathogens were identified in less than 50% of ILI cases occurred during a high activity influenza season. The detection of other than influenza viruses was sporadic, without evidence of large outbreaks due to specific agents.

Adolescent↗

Viral, mycoplasma and bacterial infections in nurses with symptoms of respiratory diseases.

A consecutive series of 282 nurses of the University Hospital, Groningen, with complaints of the nose and/or throat associated with coughing and/or hoarseness were examined between April 1965 and February 1968. The intent was to obtain information on the incidence of viral, mycoplasma and bacterial infections, and on the relationship of these infections in nurses with chronic nonspecific lung disease (CNSLD). The following results were obtained: 1. Virus infections caused by influenza virus (A, B, and C), rhinovirus, parainfluenza virus, adenovirus, respiratory syncytial virus and/or Mycoplasma pneumoniae were confirmed in 30% of the nurses examined; if influenza was excluded, this figure was 20%. 2. Rhinovirus infections were found more often than all the other virus infections together (if influenza was excluded). 3. Approximately 25% of the nurses had signs of CNSLD. 4. In the course of the virus infections, nine out of 14 nurses with a history of chronic obstructive lung disease showed symptoms of exacerbation or recurrence of a generalized bronchial obstruction. 5. There was no difference in the incidence of virus infections in the group of nurses with and without CNSLD. 6. There were more bacterial infections (without a confirmed virus infection) in the subjects with CNSLD than in those without CNSLD. 7. There were more combined viral/bacterial infections in the patients with CNSLD than in those without CNSLD. 8. Patients with influenza did not have more bacterial infections than patients with other virus infections. This is also true for patients with CNSLD and influenza when regarded separately. The patients without CNSLD tended to have more bacterial infections with influenza than with other viral infections, but the difference was not statistically significant.

Adenoviridae↗

[Use of an immune blotting method (western) for studying viral antigens and for detecting antibodies to viral proteins].

The technique of the procedure and the results of the use of immune ("western") blotting method for studies on viral antigens and detection of antibodies to individual proteins of viral particles are described. The possibility of detection and study of individual viral antigens in the whole plasma of patients or carriers is demonstrated by the example of HBs antigen of human hepatitis B virus. The method of immune blotting was used for screening of human sera for the detection of antibodies to the AIDS virus proteins. The sera under study positive for antibodies to AIDS virus by preliminary solid-phase enzyme-immunoassay were shown to contain actually the antibodies to different proteins of AIDS virus. The antibody levels to individual AIDS virus proteins varied in different sera. Some sera positive for antibodies to AIDS virus by the solid-phase enzyme-immunoassay contained no antibody to AIDS virus proteins but reacted with cellular proteins present in the antigen. The immune blotting method was also used for determinations of the spectrum of antibodies in animal sera produced by immunization with different viral antigens.

Animals↗

Presence of respiratory viruses in middle ear fluids and nasal wash specimens from children with acute otitis media.

During a 28-month period, 84 children with acute otitis media were studied by viral and bacterial cultures of middle ear fluid and viral cultures of nasal lavage fluid. Viruses were isolated from the middle ear fluid of 17 (20%) patients. Evidence of viral infection was demonstrated by positive viral cultures of middle ear fluid and/or nasal lavage fluid in 33 (39%) patients. Rhinovirus in one patient and influenza b virus in another were the only pathogens isolated. Influenza virus, enterovirus, and rhinovirus were the most common viruses found in middle ear fluids. Parainfluenza virus, adenovirus, and respiratory syncytial virus were found less often. In 82% of cases, the virus isolated from middle ear fluid was also isolated from nasal lavage fluid, but only 44% of viruses found in nasal lavage fluid were also found in middle ear fluid. Mixed bacterial and combined viral-bacterial infections were common. Only 15% of patients had no pathogen isolated from middle ear fluids. Using tissue culture techniques, we demonstrated that enterovirus and rhinovirus are also common middle ear pathogens. Our data reemphasize the significance of viruses as etiologic agents of acute otitis media and propose several questions regarding the viral-bacterial interactions and the types of viruses involved in the pathogenesis of the disease.

Acute Disease↗

[Effect of immunization with an inactivated influenza vaccine, NIVGRIP, on the viral population and clinical course of patients with chronic non-bacterial pharyngitis].

Study was conducted on 20 subjects with non bacterial chronic rhinopharyngitis. Forty-one virus strains, mainly adenoviruses, type 3 parainfluenza virus, influenza and type 1 herpes viruses, as well as enteroviruses were isolated from samples collected at regular intervals. After the NIVGRIP (R) vaccination, the number of subjects with viruses present in the pharynx decreased by 75% (from 20 to 5 positive patients) and that of isolates from 41 to 6 (80% positive samples before vaccination against 10% after immunization).

Adenoviruses, Human↗

A simian virus 5 (SV5) P/V mutant is less cytopathic than wild-type SV5 in human dendritic cells and is a more effective activator of dendritic cell maturation and function.

Human epithelial cells infected with the parainfluenza virus simian virus 5 (SV5) show minimal activation of host cell interferon (IFN), cytokine, and cell death pathways. In contrast, a recombinant SV5 P/V gene mutant (rSV5-P/V-CPI-) overexpresses viral gene products and is a potent inducer of IFN, proinflammatory cytokines, and apoptosis in these cells. In this study, we have compared the outcomes of wild-type (WT) SV5 and rSV5-P/V-CPI- infections of primary human dendritic cells (DC), important antigen-presenting cells for initiating adaptive immune responses. We have tested the hypothesis that a P/V mutant which activates host antiviral responses will be a more potent inducer of DC maturation and function than WT rSV5, which suppresses host cell responses. Infection of peripheral blood mononuclear cell-derived immature DC with WT rSV5 resulted in high levels of viral protein and progeny virus but very little increase in cell surface costimulatory molecules or secretion of IFN and proinflammatory cytokines. In contrast, immature DC infected with the rSV5-P/V-CPI- mutant produced only low levels of viral protein and progeny virus, but these infected cells were induced to secrete IFN-alpha and other cytokines and showed elevated levels of maturation markers. Unexpectedly, DC infected with WT rSV5 showed extensive cytopathic effects and increased levels of active caspase-3, while infection of DC with the P/V mutant was largely noncytopathic. In mixed-culture assays, WT rSV5-infected DC were impaired in the ability to stimulate proliferation of autologous CD4+ T cells, whereas DC infected with the P/V mutant were very effective at activating T-cell proliferation. The addition of a pancaspase inhibitor to DC infected with WT rSV5 reduced cytopathic effects and resulted in higher surface expression levels of maturation markers. Our finding that the SV5 P/V mutant has both a reduced cytopathic effect in human DC compared to WT SV5 and an enhanced ability to induce DC function has implications for the rational design of novel recombinant paramyxovirus vectors based on engineered mutations in the viral P/V gene.

Apoptosis↗

Selective STAT protein degradation induced by paramyxoviruses requires both STAT1 and STAT2 but is independent of alpha/beta interferon signal transduction.

The alpha/beta interferon (IFN-alpha/beta)-induced STAT signal transduction pathway leading to activation of the ISGF3 transcription complex and subsequent antiviral responses is the target of viral pathogenesis strategies. Members of the Rubulavirus genus of the Paramyxovirus family of RNA viruses have acquired the ability to specifically target either STAT1 or STAT2 for proteolytic degradation as a countermeasure for evading IFN responses. While type II human parainfluenza virus induces STAT2 degradation, simian virus 5 induces STAT1 degradation. The components of the IFN signaling system that are required for STAT protein degradation by these paramyxoviruses have been investigated in a series of human somatic cell lines deficient in IFN signaling proteins. Results indicate that neither the IFN-alpha/beta receptor, the tyrosine kinases Jak1 or Tyk2, nor the ISGF3 DNA-binding subunit, IFN regulatory factor 9 (IRF9), is required for STAT protein degradation induced by either virus. Nonetheless, both STAT1 and STAT2 are strictly required in the host cell to establish a degradation-permissive environment enabling both viruses to target their respective STAT protein. Complementation studies reveal that STAT protein-activating tyrosine phosphorylation and functional src homology 2 (SH2) domains are dispensable for creating a permissive STAT degradation environment in degradation-incompetent cells, but the N terminus of the missing STAT protein is essential. Protein-protein interaction analysis indicates that V and STAT proteins interact physically in vitro and in vivo. These results constitute genetic and biochemical evidence supporting a virus-induced, IFN-independent STAT protein degradation complex that contains at least STAT1 and STAT2.

Animals↗