Search Results (86)

Respiratory pathogens are significant causes of morbidity and mortality worldwide. Since the emergence of SARS-CoV-2 in 2019 and the mitigation measures implemented to control the pandemic, other respiratory viruses’ transmission and circulation patterns were substantially disrupted. We leveraged the influenza hospitalization surveillance in Tanzania to understand the distribution of respiratory viruses shortly after nonpharmaceutical interventions (NPIs) were lifted. A total of 475 samples that tested negative for SARS-CoV-2 and influenza from March through May 2022 were included in this study. The samples were tested for 16 virus targets using Anyplex II RV16 multiplex assays. The findings indicate that most hospitalizations (74%) were among children under 15 years, with human bocavirus (HBoV) being the most prevalent (26.8%), followed by rhinovirus (RV, 12.3%), parainfluenza viruses (PIVs1–4, 10.2%), respiratory syncytial virus (RSV, 8.7%), adenovirus (AdV, 4.3%), and metapneumovirus (MPV, 2.9%). Notably, 54% of respiratory hospitalizations had no viruses detected. The findings highlight the broad circulation of respiratory viruses shortly after NPIs were lifted in Tanzania. Surveillance for respiratory pathogens beyond influenza and SARS-CoV-2 can inform public health officials of emerging threats in the country and should be considered an important pandemic preparedness measure at a global level. Full article

Natural killer (NK) cell adoptive immunotherapy is a promising therapeutic approach in which NK cells perform targeted lysis of tumor cells. Oncolytic viruses are also effective cancer therapeutic agents due to their ability to selectively target and kill tumor cells. Combination therapies that integrate NK cells and oncolytic viruses have been shown to enhance tumor killing compared to individual treatment strategies alone. Using in vitro expanded human NK cells (PM21-NK cells), we tested the relative ability of tumor cells infected with WT parainfluenza virus 5 (PIV5), which is a poor inducer of type 1 interferon (IFN-I), versus PIV5 P/V gene mutant, which is a strong inducer of IFN-I synthesis, to modulate NK cell activities. Both WT and P/V mutant viruses were capable of infecting PM21-NK cells and caused extensive cytopathic effects. Co-culturing of PM21-NK cells with virus-infected tumor cells resulted in spread of WT PIV5 to naïve NK cells, but NK cells were protected from spread of the P/V mutant virus by IFN-I induction. Direct treatment of PM21-NK cells with IFN-I or media from P/V-virus-infected tumor cells enhanced NK cell cytotoxicity, at least in part due to upregulation of the death ligand, TRAIL. IFN-I-treated PM21-NK cells also showed a decrease in IFN-γ secretion, a cytokine we have previously shown to reduce PM21-NK cell tumor killing. Our results highlight multiple mechanisms by which an IFN-I-inducing oncolytic virus can enhance NK-cell-mediated killing of target virus-infected and uninfected tumor cells. Full article

Background: Pneumoviruses are etiologic agents of respiratory tract infections and a major cause of morbidity and mortality worldwide, particularly affecting young children, the elderly, and individuals with underlying clinical conditions. These viruses are associated with a significant burden, particularly in low- and middle-income countries, where reported deaths attributable to respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) in young children are important. Recent developments have been noted in the prevention of pneumoviral infections. Method: In this review, we analyzed clinical trials of the approved RSV vaccines, as well as the recent prominent platform technologies used in RSV vaccine research. In addition, we discussed combination vaccines targeting RSV, HMPV, and Human Parainfluenza Virus Type 3 (HPIV3) that have entered clinical trials. Results: Recent advancements include the approval of three RSV vaccine candidates: AREXVY^®(GSK), ABRYSVO^®(Pfizer), and mRESVIA^®(Moderna). These vaccines are primarily intended for older adults, with ABRYSVO^® also capable of providing passive immunization to infants via maternal administration. The review highlights RSV vaccine platform technologies and combination vaccines currently being evaluated in clinical settings. Conclusions: While significant progress has been made in RSV vaccine development, especially with three approved candidates, the development of vaccines for HMPV remains an unmet medical need. Ongoing research in combination vaccines holds promise for broader protection against multiple respiratory viruses in the future. Full article

Background/Objectives: Human parainfluenza virus type 1 (hPIV-1) is a major cause of serious respiratory diseases in young children. Annually, hPIV-1 results in approximately 10,000 hospitalizations in the United States due to croup, bronchiolitis, and/or pneumonia, and 10,000 deaths worldwide due to acute lower respiratory tract infections among children less than 5 years of age. Despite the burden of disease, no vaccine for hPIV-1 is currently approved. Sendai virus (SeV) is a murine PIV-1. It has structural similarities with hPIV-1 and is currently under clinical development as an hPIV-1 Jennerian vaccine. Attributes of SeV include the following: (a) needleless delivery, (b) rapid and durable serum antibody responses after a single intranasal administration, (c) durable IgG and IgA responses in the nasal mucosa, and (d) use as a platform for recombinant vaccines against multiple pediatric pathogens. Evaluation of the tolerability, safety, and immunogenicity of intranasal SeV in healthy adults and seropositive children 3 to 6 years of age was previously conducted and supported vaccine advancement to evaluation in younger children. Methods: Three seropositive children 1 to 2 years of age received a single intranasal dose of 5 × 10⁵ EID₅₀ SeV (SENDAI, Clinicaltrials.gov NCT00186927). Adverse events were collected for 28 days post-vaccine administration using diary cards and participants were followed for six months in total. Sera were collected longitudinally for clinical laboratory and virus-specific antibody tests. Nasal swabs were collected longitudinally for virus and mucosal antibody tests. Results: Intranasal SeV was well tolerated, with only mild grade 1–2 events that resolved spontaneously. No serious adverse events, medically attended adverse events, or adverse events causing protocol termination were reported. One participant had positive nasal swabs for inoculated SeV during the first week after vaccination. Although children had measurable PIV-1-specific serum antibodies at baseline, intranasal SeV vaccination resulted in significant serum antibody increases in all participants. Similarly, there were significant increases in PIV-1-specific nasal IgG and IgA levels in all participants. Elevated antibody levels persisted through the six months of follow-up. Conclusions: Intranasal SeV was well tolerated and uniformly immunogenic in seropositive children 1 to 2 years of age. Results encourage the further evaluation of SeV and SeV-based recombinants as potential intranasal vaccines for the prevention of infection by hPIV-1 and other serious respiratory pathogens. Full article

The rapid and accurate detection of viral infections is of paramount importance, given their widespread impact across diverse demographics. Common viruses such as influenza, parainfluenza, rhinovirus, and adenovirus contribute significantly to respiratory illnesses. The pathogenic nature of certain viruses, characterized by rapid mutations and high transmissibility, underscores the urgent need for dynamic detection methodologies. Quantitative reverse transcription PCR (RT-qPCR) remains the gold-standard diagnostic tool. Its reliance on costly equipment, reagents, and skilled personnel has driven explorations of alternative approaches, such as catalytic DNA nanomachines. Diagnostic platforms using catalytic DNA nanomachines offer amplification-free nucleic acid detection without the need for protein enzymes and demonstrate feasibility and cost-effectiveness for both laboratory and point-of-care diagnostics. This study focuses on the development of multicomponent DNA nanomachines with catalytic proficiency towards a fluorescent substrate, enabling the generation of a fluorescent signal upon the presence of target nucleic acids. Specifically tailored variants are designed for detecting human parainfluenza virus type 3 (HPIV) and respiratory syncytial virus (RSV). The engineered DNA nanomachine features six RNA-binding arms for recognition and unwinding of RNA secondary structures, along with a catalytic core for nucleic acid cleavage, indicating potential utility in real clinical practice with minimal requirements. This research showcases the potential of DNA nanomachines as a reliable and sensitive diagnostic tool for RNA virus identification, offering promising prospects for clinical applications in the realm of infectious disease management. Full article

RNA viruses pose a significant global public health burden due to their high mutation rates, zoonotic potential, and ability to evade immune responses. A common aspect of their replication is the generation of defective interfering particles (DIPs), which contain truncated defective viral genomes (DVGs) that depend on full-length standard (STD) virus for replication. DVGs have gained recognition as they are increasingly detected in clinical samples from natural infections. While their role in modulating type I interferon (IFN-I) responses is well established, their impact on the complement (C′) system is not understood. In this study, we examined how DVGs influence C′-mediated lysis during parainfluenza virus 5 (PIV5) infection using real-time in vitro cell viability assays. Our results demonstrated that C′ effectively killed human lung epithelial cells infected with STD PIV5, whereas co-infection with DIP-enriched stocks significantly suppressed C′-mediated killing through mechanisms that were dependent on DVG replication but independent of IFN-I production. The titration of DI units in co-infection with STD PIV5 showed a strong linear relationship between DIP-mediated decreases in surface viral glycoprotein expression and the inhibition of C′-mediated lysis. Our findings reveal a previously unrecognized function of DVGs in modulating C′ pathways, shedding light on their potential role in viral persistence and immune evasion. Full article

Influenza A virus is responsible for annual epidemics and occasional pandemics leading to significant mortality and morbidity in human populations. Parainfluenza viruses also contribute to lung infections and chronic lung disease. In this study, we investigated the effect of high glucose on the productivity of influenza A and Sendai (murine parainfluenza type 1) viruses in A549 immortalized cells. A glycolytic pattern of infection was determined by monitoring the release of lactate and phosphofructokinase (PFK) activity in infected and uninfected cells. qRT-PCR was used to analyze the expression of viral and cellular cytokine mRNA levels in cultured cells. The data show that the productivity of both influenza and Sendai viruses was reduced in A549 cells cultured in high-glucose conditions. This was accompanied by increased lactate production and altered PFK activity profile. Endogenous or virus infection-induced interferon β (IFN-β) mRNA expression was significantly decreased in high glucose compared to normal glucose status during early times of infection. Unlike in Sendai virus-infected cells, H1N1 virus reversed the significant increase in transforming growth factor β1 (TGF-β1) mRNA expression due to increased glucose concentration during early infection times. In conclusion, high glucose may have a negative effect on influenza and parainfluenza productivity in vitro. This effect may be considered when evaluating personalized therapeutic/diagnostic markers in infection-accompanied hyperglycemic status. Full article

Background: To provide clues and a diagnostic basis for patients with fever of unknown origin through urinary proteomics analysis. Methods: For the first time, an attempt was made to conduct a full-library search for viruses in urine samples. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) technology was employed to analyze the urinary proteomes of patients with fever of unknown origin, and to search for and identify viral protein fragments. In this study, there is no need to pre-determine the types of substances present in the samples. As long as the relevant sequences of viruses are available in the database, virus searches can be performed on the samples. Results: In the urine samples, multiple specific peptides from various viruses, such as the monkeypox virus, salivirus A, human herpesvirus 8 type P, Middle East respiratory syndrome-related coronavirus, rotavirus A, Orf virus (strain NZ2), human herpesvirus 2 (strain HG52), human adenovirus E serotype 4, influenza A virus, human coronavirus NL63, parainfluenza virus 5 (strain W3), Nipah virus, and hepatitis C virus genotype 2k (isolate VAT96), could be observed. It was found that the detection amounts of multiple viruses in febrile patients were much higher than those in the control group. Among them, the increase multiple of salivirus A was as high as more than 4200 times, and the increase multiples of multiple viral proteins were higher than 20 times. Conclusions: Viral fragments in urinary proteins can be reliably identified using mass spectrometry, which provides clues for the investigation of unexplained fever and may also be applied to the exploration of any unknown diseases. Full article

Acute pharyngotonsillitis is a common reason to visit primary care providers. Group A Streptococcal (GAS) pharyngitis is the most common bacterial infection which needs antibiotic treatment. GAS accounts for only 10–15% of adult acute pharyngitis cases. The overuse of antibiotics for viral pharyngotonsillitis is common and may lead to inappropriate antimicrobial stewardship and the emergence of bacterial resistance. However, the etiology of acute pharyngotonsillitis for hospitalized adult patients is rarely studied. So, we reported the 10-year surveillance data of hospitalized adult patients with acute pharyngotonsillitis in a regional hospital in Taiwan. Every consecutive adult patient admitted with acute pharyngotonsillitis in 2011–2021 was recruited for a complete etiology study. The etiology of acute pharyngotonsillitis was identified in 117 patients. Overall, 42 herpes simplex virus cases, 26 adenovirus cases, 16 acute human immunodeficiency virus cases, 12 influenza cases, three parainfluenza cases, six Epstein–Barr virus cases, one cytomegalovirus case, four enterovirus cases, one varicella-zoster virus case, four Mycoplasma pneumoniae cases, one Chlamydophila pneumoniae case, and only one GAS case were identified. The average of the points for the Modified Centor Criteria was 1.38 (55% of patients with 0–1 points and 45% with 2–3 points). However, 88.9%of patients received antibiotics at the emergency department, and 76.9%also received antibiotics while hospitalized. Only a few patients required antibiotic treatment, while the majority of patients with viral illness needed only symptomatic treatment. However, distinguishing viral etiology from GAS pharyngitis is challenging even in the presence of tonsil exudates, high C-reactive protein, and leukocytosis. A diagnostic algorithm and the application of the Modified Centor Criteria should be considered for hospitalized adults with acute pharyngotonsillitis to improve antimicrobial stewardship. Full article

Background. Influenza remains a significant public health issue, with seasonal trends varying across regions. This study provides a comprehensive analysis of influenza virus trends in Italy, leveraging epidemiological and virological data from the Istituto Superiore di Sanità (ISS). The primary objective is to assess influenza activity at both national and regional levels, highlighting variations in incidence rates and viral subtype circulation during the 2023/2024 season. Methods. We conducted a systematic approach to data collection, processing, and visualization, utilizing influenza surveillance data from ISS. Incidence rates, subtype distribution, and co-circulating respiratory viruses were analyzed to identify key trends. Results. Our findings reveal a significant increase in influenza cases during the 2023/2024 season, with incidence rates surpassing pre-pandemic levels. Notably, changes in the circulation of influenza A(H3N2) and influenza B were observed, alongside the presence of other respiratory viruses such as RSV and rhinovirus. Conclusions. This study underscores the importance of real-time surveillance, transparent data sharing, and advanced visualization tools in guiding public health responses. By integrating lessons from COVID-19, we highlight the necessity of standardized surveillance frameworks to enhance preparedness for future seasonal outbreaks and potential pandemics. Full article

Human parainfluenza virus type 2 (HPIV2) is a clinically significant respiratory pathogen, which highlights the necessity of studies on its molecular evolution. This study investigated the evolutionary dynamics, phylodynamics, and structural characteristics of the HPIV2 fusion (F) gene using a comprehensive dataset spanning multiple decades and geographic regions. Phylogenetic analyses revealed two distinct clusters of HPIV2 F gene sequences, which were estimated to have diverged from a common ancestor approximately a century ago. Cluster 1 demonstrated a higher evolutionary rate and genetic diversity compared to the more stable cluster 2. Bayesian Skyline Plot analyses indicated a significant increase in the effective population size of the F gene between 2005 and 2015; potentially linked to enhanced diagnostic and surveillance capabilities. Structural modeling identified conserved conformational epitopes predominantly in the apex and stalk regions of the F protein. These findings underscore the evolutionary constraints and antigenic landscape of the HPIV2 F protein. Full article

Respiratory viral infections present significant global health challenges, causing substantial morbidity and mortality, particularly among highly susceptible components of the population. The emergence of pandemics and epidemics, such as those caused by influenza viruses and coronaviruses, emphasizes the urgent need for effective antiviral therapeutics. In this review, we explore the potential of broad-spectrum antiviral agents targeting respiratory RNA viruses, including influenza viruses, coronaviruses, respiratory syncytial virus, human metapneumovirus, human parainfluenza viruses, and rhinoviruses. Various broad-spectrum direct-acting and host-targeting antivirals are discussed, including monoclonal antibodies targeting conserved regions of viral surface proteins, molecules interfering with host cell receptors or viral replication machinery, viral protease inhibitors, siRNA therapies, ribonuclease, and 3D8 scFv. Advancements in host-targeting approaches to reduce resistance and RNA-based therapeutics offer significant potential for combating respiratory viral threats. Despite challenges, broad-spectrum antiviral agents represent a crucial strategy, particularly when specific viral pathogens are unidentified or rapid intervention is essential, such as during pandemics or outbreaks. Full article

To better understand the phylogenomics of the hemagglutinin-neuraminidase (HN) gene and HN protein in human parainfluenza virus type 4 (HPIV4), we performed phylogenomic analyses using various bioinformatics methods. The main bioinformatics analyses included a time-scaled phylogeny, genetic distance assessments, and three-dimensional (3D) structure mapping of the HN protein with conformational epitope and selective pressure analyses. The time-scaled phylogenetic tree indicated that the most recent common ancestor of the HN gene emerged approximately 100 years ago. Additionally, the tree revealed two distinct clusters corresponding to HPIV4a and HPIV4b. The divergence times for the most recent common ancestors of the HN gene in HPIV4a and HPIV4b strains were estimated to be around 1993 and 1986, respectively. The evolutionary rates of the gene varied significantly between clusters, ranging from approximately 1.2 × 10⁻³ to 8.7 × 10⁻⁴ substitutions per site per year. Genetic distances within each cluster were relatively short (less than 0.04). Phylodynamic analyses demonstrated an increase in the genome population size around the year 2000. Structural analyses revealed that the active sites of the HN protein were located at the protein’s head. Furthermore, the most conformational epitopes were located in adjacent active sites of the protein. These results suggested that reinfection may be unlikely to occur in the case of most HPIV4. Together, the HN gene and protein of HPIV4 strains isolated in Japan have undergone unique evolutionary changes. In addition, antibodies targeting the conformational epitopes of the HPIV4 HN protein may contribute to protection against the virus. Full article

Human parainfluenza virus type 3 (HPIV-3) can cause severe respiratory diseases, particularly in young children, the elderly and immunocompromised. There are no approved antiviral drugs against this virus. We report that the combination of ribavirin with either remdesivir or its parent nucleoside GS-441524 results in a pronounced antiviral effect against HPIV-3 in LLC-MK2 cells and in human airway epithelial cells grown at the air–liquid interface. In AG129 mice intranasally inoculated with HPIV-3, the combined treatment with ribavirin and GS-441524 decreased infectious viral lung titers by >2.5 log₁₀ to undetectable levels in 4 out of 11 mice and by 1.6 log₁₀ in the remaining 7 mice as compared with the vehicle. The lungs of all mice that received the combined treatment appeared histologically normal or virtually normal, whereas 8 of 11 vehicle-treated mice presented with bronchopneumonia. By contrast, ribavirin alone did not result in a reduction in infectious viral lung titers; GS-441524 alone reduced infectious viral lung titers by 1.2 log₁₀. Moreover, several mice in the single-treatment groups exhibited severe lung pathology. These findings may warrant exploring this combination in patients with severe HPIV-3 infections and possibly also against infections with other viruses that are susceptible in vitro to these two drugs. Full article

Human parainfluenza virus (HPIV) is a major cause of respiratory illnesses in children under five years, with clinical manifestations ranging from mild upper respiratory tract infections to severe lower respiratory tract diseases. This multi-center, cross-sectional study investigated the burden, clinical features, and predictors of respiratory viral infections in hospitalized children across four sites in Jordan. Nasopharyngeal specimens from 1000 eligible children were analyzed. In this article, we focused on HPIV infections. The overall HPIV positivity rate was 22.6%, with HPIV-3 accounting for 90.3% of cases. Significant geographic variability was observed, with higher positivity rates in the southern region. HPIV-positive cases frequently presented with symptoms like nasal congestion, tachypnea, and poor feeding. Co-infections with respiratory syncytial virus (RSV) or influenza were associated with worse outcomes, including an increased need for invasive ventilation. The logistic regression identified male gender, asthma, and respiratory acidosis as predictors of complications. Geographic differences in HPIV prevalence and severity were notable, emphasizing the influence of environmental and socioeconomic factors. These findings underscore the urgent need for enhanced HPIV surveillance, targeted public health interventions, and vaccine development to mitigate the disease burden. This study provides critical insights that guide healthcare strategies and improve outcomes in young children at risk of severe HPIV infections. Full article