Cause Of Viral Respiratory Infections Research Articles

Rhinovirus as a rare cause of acute onset dilated cardiomyopathy due to myocarditis in a newborn: case report and review of the literature

Cardiomyopathies account for 1% of cardiac diseases that mainly originate from myocarditis in the form of dilated cardiomyopathy in the neonatal period. Viruses are the main cause of myocarditis resulting in dilated cardiomyopathy. Rhinovirus is the leading cause of viral respiratory infections though it is rarely severe. We report a 17 day old newborn with acute onset dilated cardiomyopathy due to myocarditis that developed after a viral respiratory infection caused by Rhinovirus who was admitted to the emergency ward with shock due to heart failure and recovered without any complications. This is the first case reporting the causal role of rhinovirus and myocarditis in the neonatal period. A comprehensive approach is needed for the diagnosis of myocarditis in the case of unknown etiology and an extensive respiratory panel may be taken into consideration if there is a history or clinical symptoms of respiratory infection.

Antibody recognition of the Pneumovirus fusion protein trimer interface.

Human metapneumovirus (hMPV) is a leading cause of viral respiratory infection in children, and can cause severe lower respiratory tract infection in infants, the elderly, and immunocompromised patients. However, there remain no licensed vaccines or specific treatments for hMPV infection. Although the hMPV fusion (F) protein is the sole target of neutralizing antibodies, the immunological properties of hMPV F remain poorly understood. To further define the humoral immune response to the hMPV F protein, we isolated two new human monoclonal antibodies (mAbs), MPV458 and MPV465. Both mAbs are neutralizing in vitro and were determined to target a unique antigenic site using competitive biolayer interferometry. We determined both MPV458 and MPV465 have higher affinity for monomeric hMPV F than trimeric hMPV F. MPV458 was co-crystallized with hMPV F, and the mAb primarily interacts with an alpha helix on the F2 region of the hMPV F protein. Surprisingly, the major epitope for MPV458 lies within the trimeric interface of the hMPV F protein, suggesting significant breathing of the hMPV F protein must occur for host immune recognition of the novel epitope. In addition, significant glycan interactions were observed with a somatically mutated light chain framework residue. The data presented identifies a novel epitope on the hMPV F protein for epitope-based vaccine design, and illustrates a new mechanism for human antibody neutralization of viral glycoproteins.

Salinomycin Inhibits Influenza Virus Infection by Disrupting Endosomal Acidification and Viral Matrix Protein 2 Function

Screening of chemical libraries with 2,000 synthetic compounds identified salinomycin as a hit against influenza A and B viruses, with 50% effective concentrations ranging from 0.4 to 4.3 μM in cells. This compound is a carboxylic polyether ionophore that exchanges monovalent ions for protons across lipid bilayer membranes. Monitoring the time course of viral infection showed that salinomycin blocked nuclear migration of viral nuclear protein (NP), the most abundant component of the viral ribonucleoprotein (vRNP) complex. It caused cytoplasmic accumulation of NP, particularly within perinuclear endosomes, during virus entry. This was primarily associated with failure to acidify the endosomal-lysosomal compartments. Similar to the case with amantadine (AMT), proton channel activity of viral matrix protein 2 (M2) was blocked by salinomycin. Using purified retroviral Gag-based virus-like particles (VLPs) with M2, it was proved that salinomycin directly affects the kinetics of a proton influx into the particles but in a manner different from that of AMT. Notably, oral administration of salinomycin together with the neuraminidase inhibitor oseltamivir phosphate (OSV-P) led to enhanced antiviral effect over that with either compound used alone in influenza A virus-infected mouse models. These results provide a new paradigm for developing antivirals and their combination therapy that control both host and viral factors.IMPORTANCE Influenza virus is a main cause of viral respiratory infection in humans as well as animals, occasionally with high mortality. Circulation of influenza viruses resistant to the matrix protein 2 (M2) inhibitor, amantadine, is highly prevalent. Moreover, the frequency of detection of viruses resistant to the neuraminidase inhibitors, including oseltamivir phosphate (OSV-P) or zanamivir, is also increasing. These issues highlight the need for discovery of new antiviral agents with different mechanisms. Salinomycin as the monovalent cation-proton antiporter exhibited consistent inhibitory effects against influenza A and B viruses. It plays multifunctional roles by blocking endosomal acidification and by inactivating the proton transport function of M2, the key steps for influenza virus uncoating. Notably, salinomycin resulted in marked therapeutic effects in influenza virus-infected mice when combined with OSV-P, suggesting that its chemical derivatives could be developed as an adjuvant antiviral therapy to treat influenza infections resistant or less sensitive to existing drugs.

Synthesis and anti-rhinovirus activity of novel 3-[2-(pyridinyl)vinyl]substituted -2H-chromenes and -4H-chromen-4-ones

Human rhinoviruses (HRVs) are the most common cause of viral respiratory infections and their complications. So far, no anti-viral agent has been approved for prevention or treatment of HRV infections. Pursuing our researches on small molecules with anti-rhinovirus activity, in this paper we describe the synthesis and in vitro anti-HRV 1B and 14 properties of new [2-(2H-chromen-3-yl)vinyl]pyridines and 3-[2-(pyridinyl)vinyl]-4H-chromen-4-ones. Generally, the synthesized compounds interfered with the replication of both serotypes at the micromolar or submicromolar concentrations. Preliminary results on their mechanism of action, performed on selected (E)-2-[2-(2H-chromen-3-yl)vinyl]pyridine, indicate an interference with the early step(s) of HRV 1B and 14 replication, probably at the uncoating level.

Respiratory Syncytial Virus Matrix Protein Induces Lung Epithelial Cell Cycle Arrest through a p53 Dependent Pathway

Respiratory syncytial virus (RSV) is the major cause of viral respiratory infections in children. Our previous study showed that the RSV infection induced lung epithelial cell cycle arrest, which enhanced virus replication. To address the mechanism of RSV-induced cell cycle arrest, we examined the contribution of RSV-matrix (RSV-M) protein. In this report, we show that in both the A549 cell line and primary human bronchial epithelial (PHBE) cells, transfection with RSV-M protein caused the cells to proliferate at a slower rate than in control cells. The cell cycle analysis showed that RSV-M protein induced G1 phase arrest in A549 cells, and G1 and G2/M phase arrest in PHBE cells. Interestingly, RSV-M expression induced p53 and p21 accumulation and decreased phosphorylation of retinoblastoma protein (Rb). Further, induction of cell cycle arrest by RSV-M was not observed in a p53-deficient epithelial cell line (H1299). However, cell cycle arrest was restored after transfection of p53 cDNA into H1299 cells. Taken together, these results indicate that RSV-M protein regulates lung epithelial cell cycle through a p53-dependent pathway, which enhances RSV replication.

Simultaneous detection of respiratory syncytial virus types A and B and influenza virus types A and B in community-acquired pneumonia by reverse transcription-multiplex PCR

BackgroundRespiratory syncytial virus (RSV) types A and B and influenza A and B cause about 80–90% of viral lower respiratory tract infections. It is impossible to distinguish the cause of viral respiratory infections by their clinical presentation. Multiplex RT-PCR has a significant advantage in that it permits the simultaneous amplification of several viruses in a single reaction facilitating cost-effective diagnosis and perhaps improved clinical management. ObjectivesIn this study, our aim was to determine the prevalence of influenza A and B, and RSV types A and B among children with CAP, by the use of the newly developed rapid, accurate, and pathogen-specific technique of multiplex RT-PCR in order to accomplish the greatest positive effect on patient care and health care costs. Study methodologyThis study is a cross-sectional study involving 24 children admitted to the Children’s Hospital of the Ain Shams University due to severe lower respiratory tract infection (LRTI). Clinical and radiological assessment of all patients was performed followed by the molecular analysis of both respiratory and blood samples of all enrolled patients simultaneously by the use of the newly available reverse transcription-multiplex PCR technique (RT-m PCR). ResultsViral pneumonia was detected in one-third of enrolled patients (8/24), with the predominance of respiratory syncytial virus A (4/8), followed by influenza A virus (3/8) and influenza B virus (1/8) while no cases of respiratory syncytial virus B was detected. The same results were identified in both blood and respiratory specimens. ConclusionReverse transcription-multiplex PCR technique – multiplex has a significant advantage in that it permits the simultaneous amplification of several viruses in a single reaction making it well suited for use in epidemiological studies and to improve etiology-directed clinical management of viral pneumonia.

Vaccination of commercial broiler chicks against avian metapneumovirus infection: a comparison of drinking-water, spray and oculo-oral delivery methods

Avian metapneumovirus (aMPV) has become an important cause of viral respiratory infections in turkey and chickens. Live and inactivated vaccinations are available worldwide for prevention of disease and economic losses caused by this pathogen. The efficacy of these vaccines is vigorously tested under laboratory conditions prior to use in the field. In this study, a live subtype B aMPV vaccine was administered by spray, drinking water or oculo-oral methods to separate groups of broiler chicks under field conditions. Following this, the chicks were immediately transferred to separate rooms in an experimental isolation house, monitored and challenged with virulent subtype B aMPV. No clinical signs were recorded following the vaccination methods. In the oculo-oral vaccinated chicks, 40–60% of the birds were vaccine virus positive by RT-PCR. In addition, in comparison to other groups, statistically higher levels of aMPV ELISA antibodies were detected. After spray vaccination, the number of chicks positive for the vaccine virus increased gradually from 10% at one week to 30% by 3 weeks post vaccination. Following drinking water vaccination, 30% of chicks were aMPV positive at 1 week but negative by 3 weeks post vaccination. In both, spray and drinking water vaccinated groups, no ELISA antibodies were detected, but when challenged all chicks were protected against disease. At 5 days post challenge, 100% of chicks in the unvaccinated and those vaccinated by spray or drinking water routes but only 20% of the oculo-oral-vaccinated chicks were aMPV positive by RT-PCR. At 10 days post challenge, 10% of chicks in each group were aMPV RT-PCR positive. On challenge, all vaccinated chicks were protected against disease. It appears that when aMPV vaccine is accurately applied to chicks by spray or drinking water routes, both are capable of giving protection against clinical disease equal to that induced in those chicks vaccinated individually by the oculo-oral route.

Clinical and genetic diversity of rhinoviruses

Human rhinoviruses are the most common cause of viral respiratory infections across all age groups, from the neonate to the elderly patient. The benign nature of most of these infections as well as the difficulty to isolate the causative agent limits our perception of its real clinical impact. Molecular diagnostic tools have allowed to better characterize the variety of clinical presentations which are not limited to the common cold alone. It is now clearly established that rhinoviruses infect both the upper and lower tracheobronchial tree which may also be the site of viral replication. Moreover, the virus is the cause of significant complications in patients at risk such as those with asthma or highly immunocompromised hosts. The use of molecular screening techniques shows the very high diversity of circulating strains which are not only limited to known serotypes and has allowed the identification of new subgroups previously unknown. Detailed analysis of the genomic organization shows a common phylogeny between certain subgroups of rhinoviruses and enteroviruses and sheds light on the constraints modelling the evolution of human Picornaviridae. Furthermore, detailed analysis of the CRE structures shows that this structure is not only conserved for each species, but is also located on a specific region for each of these species.

Role of Metapneumovirus in Viral Respiratory Infections in Young Children

The contribution of human metapneumovirus (hMPV) relative to that of other respiratory viruses as a cause of respiratory infections in children less than 1 year old has been evaluated. From October 2003 to April 2004, nasopharyngeal samples from 211 children less than 1 year old were analyzed to detect respiratory viruses. Respiratory syncytial virus (RSV) was the predominant virus isolated (96 children [45.5%]), followed by influenza A virus, parainfluenza virus, adenovirus, cytomegalovirus, and herpes simplex virus type 1, which were only occasionally detected. From January 2004 to April 2004, a nested retrotranscription-PCR, using in-house primers directed to the matrix protein gene of hMPV, was carried out on samples in which no other viruses were detected. hMPV was detected in 18 (16.2%) children, indicating that this virus was the second-most-frequent cause of viral respiratory infections in children less than 1 year old. The rate of hospitalization for RSV- and hMPV-infected children was higher than 75%. While RSV had a peak from December to February, hMPV was increasingly detected from January to April. The mean age of hMPV-infected children (6.44 +/- 3.64 [mean +/- standard deviation] months) was significantly higher than that of RSV-infected children (3.99 +/- 2.96 [mean +/- standard deviation] months). On the other hand, 64.3% of the RSV-infected children and 12.5% of the hMPV-infected children showed high levels of C-reactive protein. Although several authors have reported that clinical symptoms of hMPV-positive patients mirrored those of RSV-positive patients, differences between the two viruses can be found.

Cost burden of viral respiratory infections: Issues for formulary decision makers

Viral respiratory infections (VRIs) are a common malady associated with considerable costs in terms of decreased productivity and time lost from work or school, visits to health-care providers, and the amount of drugs prescribed. Both total respiratory illness and rhinovirus infection peak during the fall and spring seasons, although the average percentage of office visits by patients with a rhinovirus infection is moderately high throughout the year. Most common cold remedies are relatively ineffective and may produce side effects that contribute to increased health-care costs. Antibiotic therapy is widely overused and misused despite evidence that antibiotics fail to treat the cause of VRI or prevent secondary bacterial infections. Increasing use of antibiotics has a significant impact on health-care costs and the emergence of antimicrobial resistance. Reasons for overprescribing antibiotics are varied, but they often involve physician and patient attitudes and expectations. Although treatment of VRIs poses challenges for effective formulary management, several steps can be taken to facilitate the introduction of antiviral agents, including patient and provider education, the development of rapid diagnostic tests, and medical-economics studies to determine the true cost of antiviral therapy.

Cost burden of viral respiratory infections: issues for formulary decision makers

Viral respiratory infections (VRIs) are a common malady associated with considerable costs in terms of decreased productivity and time lost from work or school, visits to health-care providers, and the amount of drugs prescribed. Both total respiratory illness and rhinovirus infection peak during the fall and spring seasons, although the average percentage of office visits by patients with a rhinovirus infection is moderately high throughout the year. Most common cold remedies are relatively ineffective and may produce side effects that contribute to increased health-care costs. Antibiotic therapy is widely overused and misused despite evidence that antibiotics fail to treat the cause of VRI or prevent secondary bacterial infections. Increasing use of antibiotics has a significant impact on health-care costs and the emergence of antimicrobial resistance. Reasons for overprescribing antibiotics are varied, but they often involve physician and patient attitudes and expectations. Although treatment of VRIs poses challenges for effective formulary management, several steps can be taken to facilitate the introduction of antiviral agents, including patient and provider education, the development of rapid diagnostic tests, and medical-economics studies to determine the true cost of antiviral therapy.