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International Journal of Biological... 2021Respiratory syncytial virus (RSV) is one of the most important viral pathogens causing respiratory tract infection in infants, the elderly and people with poor immune... (Review)
Review
Respiratory syncytial virus (RSV) is one of the most important viral pathogens causing respiratory tract infection in infants, the elderly and people with poor immune function, which causes a huge disease burden worldwide every year. It has been more than 60 years since RSV was discovered, and the palivizumab monoclonal antibody, the only approved specific treatment, is limited to use for passive immunoprophylaxis in high-risk infants; no other intervention has been approved to date. However, in the past decade, substantial progress has been made in characterizing the structure and function of RSV components, their interactions with host surface molecules, and the host innate and adaptive immune response to infection. In addition, basic and important findings have also piqued widespread interest among researchers and pharmaceutical companies searching for effective interventions for RSV infection. A large number of promising monoclonal antibodies and inhibitors have been screened, and new vaccine candidates have been designed for clinical evaluation. In this review, we first briefly introduce the structural composition, host cell surface receptors and life cycle of RSV virions. Then, we discuss the latest findings related to the pathogenesis of RSV. We also focus on the latest clinical progress in the prevention and treatment of RSV infection through the development of monoclonal antibodies, vaccines and small-molecule inhibitors. Finally, we look forward to the prospects and challenges of future RSV research and clinical intervention.
Topics: Antiviral Agents; Genome, Viral; Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Viral Vaccines
PubMed: 34671221
DOI: 10.7150/ijbs.64762 -
Presse Medicale (Paris, France : 1983) Sep 2022Measles is a highly contagious viral disease transmitted by aerosols through human-to-human contact. It is often considered as a benign disease, although mortality...
Measles is a highly contagious viral disease transmitted by aerosols through human-to-human contact. It is often considered as a benign disease, although mortality remains high in developing countries (>5%). Frequent complications (diarrhea, otitis, pneumonia, encephalitis) can be observed. The disease mainly affects young children from 5 to 6 months of age with a mortality peak in the first three years of life. The Persian physician Rhazes gave the first clinical description of the disease in the 10th century, clearly differentiating it from smallpox. Measles spread worldwide from the Renaissance. Its epidemiology was remarkably studied in 1846 by a Danish physician, Peter Panum, during an epidemic in the Faroe Islands. The viral nature of this disease was demonstrated in 1911 and the virus was identified in 1954 by Thomas Peebles and John Enders. It is a morbillivirus (family Paramyxoviridae), also responsible for rinderpest (ovine, bovine), distemper (canine, feline), and epidemic diseases of dolphins, porpoises and seals. The current measles virus appeared recently from the rinderpest virus around the 6th century BCE. It has adapted perfectly to the human species, becoming strictly human, without animal reservoirs. A live attenuated vaccine was developed in 1958 by Enders' team after numerous passages in cell cultures. The vaccine was licensed in the United States in 1963 and is used on a large scale by the WHO throughout the world. This highly effective and well-tolerated vaccine has greatly reduced the number of measles cases and saved millions of lives. Measles remains a major public health concern, causing over 100,000 deaths per year worldwide. Today, the most affected continents remain Africa, South America and Asia.
Topics: Child; Animals; Dogs; Cattle; Cats; Sheep; Humans; United States; Child, Preschool; Measles; Morbillivirus; Measles virus; Rinderpest virus; Asia
PubMed: 36414136
DOI: 10.1016/j.lpm.2022.104149 -
Current Opinion in Virology Aug 2023Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) continue to be a global burden to infants, the elderly, and immunocompromised individuals. In the past... (Review)
Review
Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) continue to be a global burden to infants, the elderly, and immunocompromised individuals. In the past ten years, there has been substantial progress in the development of new vaccine candidates and therapies against these viruses. These advancements were guided by the structural elucidation of the major surface glycoproteins for these viruses, the fusion (F) protein and attachment (G) protein. The identification of immunodominant epitopes on the RSV F and hMPV F proteins has expanded current knowledge on antibody-mediated immune responses, which has led to new approaches for vaccine and therapeutic development through the stabilization of pre-fusion constructs of the F protein and pre-fusion-specific monoclonal antibodies with high potency and efficacy. In this review, we describe structural characteristics of known antigenic sites on the RSV and hMPV proteins, their influence on the immune response, and current progress in vaccine and therapeutic development.
Topics: Humans; Aged; Metapneumovirus; Antibodies, Viral; Antibodies, Neutralizing; Viral Fusion Proteins; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections
PubMed: 37544710
DOI: 10.1016/j.coviro.2023.101337 -
Viruses Sep 2023Respiratory syncytial virus (RSV) infections are a constant public health problem, especially in infants and older adults. Virtually all children will have been infected... (Review)
Review
Respiratory syncytial virus (RSV) infections are a constant public health problem, especially in infants and older adults. Virtually all children will have been infected with RSV by the age of two, and reinfections are common throughout life. Since antigenic variation, which is frequently observed among other respiratory viruses such as SARS-CoV-2 or influenza viruses, can only be observed for RSV to a limited extent, reinfections may result from short-term or incomplete immunity. After decades of research, two RSV vaccines were approved to prevent lower respiratory tract infections in older adults. Recently, the FDA approved a vaccine for active vaccination of pregnant women to prevent severe RSV disease in infants during their first RSV season. This review focuses on the host response to RSV infections mediated by epithelial cells as the first physical barrier, followed by responses of the innate and adaptive immune systems. We address possible RSV-mediated immunomodulatory and pathogenic mechanisms during infections and discuss the current vaccine candidates and alternative treatment options.
Topics: Infant; Child; Female; Pregnancy; Humans; Aged; Respiratory Syncytial Virus Infections; Reinfection; Respiratory Syncytial Viruses; Immunity; Vaccines; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human
PubMed: 37896776
DOI: 10.3390/v15101999 -
EMBO Molecular Medicine Apr 2022In virology, the term seasonality describes variations in virus prevalence at more or less regular intervals throughout the year. Specifically, it has long been...
In virology, the term seasonality describes variations in virus prevalence at more or less regular intervals throughout the year. Specifically, it has long been recognized that outbreaks of human influenza viruses, respiratory syncytial virus (RSV), and human coronaviruses occur in temperate climates during the winter season, whereas low activity is detected during the summer months. Other human respiratory viruses, such as parainfluenza viruses, human metapneumoviruses, and rhinoviruses, show highest activity during the spring or fall season in temperate regions, depending on the virus and subtype. In tropical climates, influenza viruses circulate throughout the year and no distinct seasonal patterns are observed, although virus outbreaks tend to spike during the rainy season. Overall, seasonality is more pronounced with greater distance from the equator, and tends to be less pronounced in regions closer to the equator (Li et al, 2019).
Topics: Humans; Influenza, Human; Metapneumovirus; Orthomyxoviridae; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Viruses
PubMed: 35157360
DOI: 10.15252/emmm.202115352 -
Infectious Disease Clinics of North... Mar 2024Viral pneumonia is usually community acquired and caused by influenza, parainfluenza, respiratory syncytial virus, human metapneumovirus, and adenovirus. Many of these... (Review)
Review
Viral pneumonia is usually community acquired and caused by influenza, parainfluenza, respiratory syncytial virus, human metapneumovirus, and adenovirus. Many of these infections are airway centric and chest imaging demonstrates bronchiolitis and bronchopneumonia, With the exception of adenovirus infections, the presence of lobar consolidation usually suggests bacterial coinfection. Community-acquired viral pathogens can cause more severe pneumonia in immunocompromised hosts, who are also susceptible to CMV and varicella infection. These latter 2 pathogens are less likely to manifest the striking airway-centric pattern. Airway-centric pattern is distinctly uncommon in Hantavirus pulmonary syndrome, a rare environmentally acquired infection with high mortality.
Topics: Humans; Tomography, X-Ray Computed; Pneumonia, Viral; Influenza, Human; Paramyxoviridae Infections; Metapneumovirus; Adenoviridae Infections; Community-Acquired Infections; Respiratory Tract Infections
PubMed: 38280762
DOI: 10.1016/j.idc.2023.12.009 -
Viruses Sep 2023Hendra virus (HeV) and Nipah virus (NiV) are zoonotic paramyxoviruses in the genus (HNV) that emerged nearly thirty years ago. Outbreaks of HeV and NiV have led to... (Review)
Review
Hendra virus (HeV) and Nipah virus (NiV) are zoonotic paramyxoviruses in the genus (HNV) that emerged nearly thirty years ago. Outbreaks of HeV and NiV have led to severe respiratory disease and encephalitis in humans and animals characterized by a high mortality rate. Despite the grave threat HNVs pose to public health and global biosecurity, no approved medical countermeasures for human use currently exist against HeV or NiV. To develop candidate vaccines and therapeutics and advance the field's understanding of HNV pathogenesis, animal models of HeV and NiV have been instrumental and remain indispensable. Various species, including rodents, ferrets, and nonhuman primates (NHPs), have been employed for HNV investigations. Among these, NHPs have demonstrated the closest resemblance to human HNV disease, although other animal models replicate some key disease features. Here, we provide a comprehensive review of the currently available animal models (mice, hamsters, guinea pigs, ferrets, cats, dogs, nonhuman primates, horses, and swine) to support HNV research. We also discuss the strengths and limitations of each model for conducting pathogenesis and transmission studies on HeV and NiV and for the evaluation of medical countermeasures.
Topics: Cricetinae; Animals; Humans; Guinea Pigs; Horses; Mice; Dogs; Ferrets; Henipavirus Infections; Hendra Virus; Nipah Virus; Disease Models, Animal; Primates
PubMed: 37896758
DOI: 10.3390/v15101980 -
Cell Jul 2022Stem cell research endeavors to generate specific subtypes of classically defined "cell types." Here, we generate >90% pure human artery or vein endothelial cells from...
Stem cell research endeavors to generate specific subtypes of classically defined "cell types." Here, we generate >90% pure human artery or vein endothelial cells from pluripotent stem cells within 3-4 days. We specified artery cells by inhibiting vein-specifying signals and vice versa. These cells modeled viral infection of human vasculature by Nipah and Hendra viruses, which are extraordinarily deadly (∼57%-59% fatality rate) and require biosafety-level-4 containment. Generating pure populations of artery and vein cells highlighted that Nipah and Hendra viruses preferentially infected arteries; arteries expressed higher levels of their viral-entry receptor. Virally infected artery cells fused into syncytia containing up to 23 nuclei, which rapidly died. Despite infecting arteries and occupying ∼6%-17% of their transcriptome, Nipah and Hendra largely eluded innate immune detection, minimally eliciting interferon signaling. We thus efficiently generate artery and vein cells, introduce stem-cell-based toolkits for biosafety-level-4 virology, and explore the arterial tropism and cellular effects of Nipah and Hendra viruses.
Topics: Arteries; Endothelial Cells; Hendra Virus; Humans; Nipah Virus; Pluripotent Stem Cells; Tropism
PubMed: 35738284
DOI: 10.1016/j.cell.2022.05.024 -
Clinical Infectious Diseases : An... Aug 2022To combat the coronavirus disease 2019 (COVID-19) pandemic, nonpharmaceutical interventions (NPIs) were implemented worldwide, which impacted a broad spectrum of acute... (Observational Study)
Observational Study
BACKGROUND
To combat the coronavirus disease 2019 (COVID-19) pandemic, nonpharmaceutical interventions (NPIs) were implemented worldwide, which impacted a broad spectrum of acute respiratory infections (ARIs).
METHODS
Etiologically diagnostic data from 142 559 cases with ARIs, who were tested for 8 viral pathogens (influenza virus [IFV], respiratory syncytial virus [RSV], human parainfluenza virus [HPIV], human adenovirus [HAdV], human metapneumovirus [HMPV], human coronavirus [HCoV], human bocavirus [HBoV], and human rhinovirus [HRV]) between 2012 and 2021, were analyzed to assess the changes in respiratory infections in China during the first COVID-19 pandemic year compared with pre-pandemic years.
RESULTS
Test-positive rates of all respiratory viruses decreased during 2020, compared to the average levels during 2012-2019, with changes ranging from -17.2% for RSV to -87.6% for IFV. Sharp decreases mostly occurred between February and August when massive NPIs remained active, although HRV rebounded to the historical level during the summer. While IFV and HMPV were consistently suppressed year-round, RSV, HPIV, HCoV, HRV, and HBoV resurged and went beyond historical levels during September 2020-January 2021, after NPIs were largely relaxed and schools reopened. Resurgence was more prominent among children <18 years and in northern China. These observations remain valid after accounting for seasonality and long-term trend of each virus.
CONCLUSIONS
Activities of respiratory viral infections were reduced substantially in the early phases of the COVID-19 pandemic, and massive NPIs were likely the main driver. Lifting of NPIs can lead to resurgence of viral infections, particularly in children.
Topics: COVID-19; Child; Human bocavirus; Humans; Metapneumovirus; Orthomyxoviridae; Pandemics; Parainfluenza Virus 1, Human; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Virus Diseases; Viruses
PubMed: 34788811
DOI: 10.1093/cid/ciab942 -
Cell Host & Microbe Aug 2023Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infections pose a significant health burden. Using pre-fusion conformation fusion (F) proteins, we...
Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infections pose a significant health burden. Using pre-fusion conformation fusion (F) proteins, we isolated a panel of anti-F antibodies from a human donor. One antibody (RSV-199) potently cross-neutralized 8 RSV and hMPV strains by recognizing antigenic site III, which is partially conserved in RSV and hMPV F. Next, we determined the cryoelectron microscopy (cryo-EM) structures of RSV-199 bound to RSV F trimers, hMPV F monomers, and an unexpected dimeric form of hMPV F. These structures revealed how RSV-199 engages both RSV and hMPV F proteins through conserved interactions of the antibody heavy-chain variable region and how variability within heavy-chain complementarity-determining region 3 (HCDR3) can be accommodated at the F protein interface in site-III-directed antibodies. Furthermore, RSV-199 offered enhanced protection against RSV A and B strains and hMPV in cotton rats. These findings highlight the mechanisms of broad neutralization and therapeutic potential of RSV-199.
Topics: Humans; Metapneumovirus; Antibodies, Neutralizing; Antibodies, Viral; Cryoelectron Microscopy; Respiratory Syncytial Virus, Human; Immunoglobulin Variable Region; Viral Fusion Proteins
PubMed: 37516111
DOI: 10.1016/j.chom.2023.07.002