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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 -
Annual Review of Virology Nov 2015The cultural impact of rabies, the fatal neurological disease caused by infection with rabies virus, registers throughout recorded history. Although rabies has been the... (Review)
Review
The cultural impact of rabies, the fatal neurological disease caused by infection with rabies virus, registers throughout recorded history. Although rabies has been the subject of large-scale public health interventions, chiefly through vaccination efforts, the disease continues to take the lives of about 40,000-70,000 people per year, roughly 40% of whom are children. Most of these deaths occur in resource-poor countries, where lack of infrastructure prevents timely reporting and postexposure prophylaxis and the ubiquity of domestic and wild animal hosts makes eradication unlikely. Moreover, although the disease is rarer than other human infections such as influenza, the prognosis following a bite from a rabid animal is poor: There is currently no effective treatment that will save the life of a symptomatic rabies patient. This review focuses on the major unanswered research questions related to rabies virus pathogenesis, especially those connecting the disease progression of rabies with the complex dysfunction caused by the virus in infected cells. The recent applications of cutting-edge research strategies to this question are described in detail.
Topics: Animals; Humans; Knowledge; Rabies; Rabies virus; Virulence
PubMed: 26958924
DOI: 10.1146/annurev-virology-100114-055157 -
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 -
Journal of Virology Oct 2020, known as nonsegmented negative-sense (NNS) RNA viruses, are a class of pathogenic and sometimes deadly viruses that include rabies virus (RABV), human respiratory... (Review)
Review
, known as nonsegmented negative-sense (NNS) RNA viruses, are a class of pathogenic and sometimes deadly viruses that include rabies virus (RABV), human respiratory syncytial virus (HRSV), and Ebola virus (EBOV). Unfortunately, no effective vaccines and antiviral therapeutics against many are currently available. Viral polymerases have been attractive and major antiviral therapeutic targets. Therefore, polymerases have been extensively investigated for their structures and functions. mimic RNA synthesis of their eukaryotic counterparts by utilizing multifunctional RNA polymerases to replicate entire viral genomes and transcribe viral mRNAs from individual viral genes as well as synthesize 5' methylated cap and 3' poly(A) tail of the transcribed viral mRNAs. The catalytic subunit large protein (L) and cofactor phosphoprotein (P) constitute the polymerases. In this review, we discuss the shared and unique features of RNA synthesis, the monomeric multifunctional enzyme L, and the oligomeric multimodular adapter P of We outline the structural analyses of the polymerases since the first structure of the vesicular stomatitis virus (VSV) L protein determined in 2015 and highlight multiple high-resolution cryo-electron microscopy (cryo-EM) structures of the polymerases of , namely, VSV, RABV, HRSV, human metapneumovirus (HMPV), and human parainfluenza virus (HPIV), that have been reported in recent months (2019 to 2020). We compare the structures of those polymerases grouped by virus family, illustrate the similarities and differences among those polymerases, and reveal the potential RNA synthesis mechanisms and models of highly conserved We conclude by the discussion of remaining questions, evolutionary perspectives, and future directions.
Topics: Animals; Cryoelectron Microscopy; Humans; Metapneumovirus; Models, Molecular; Mononegavirales; Protein Conformation; RNA, Messenger; RNA, Viral; RNA-Dependent RNA Polymerase; Rabies virus; Respiratory Syncytial Virus, Human; Vesicular stomatitis Indiana virus; Viral Proteins; Virus Replication
PubMed: 32847861
DOI: 10.1128/JVI.00175-20 -
Science (New York, N.Y.) Jan 2022The COVID-19 pandemic has underscored the critical need for broad-spectrum therapeutics against respiratory viruses. Respiratory syncytial virus (RSV) is a major threat...
The COVID-19 pandemic has underscored the critical need for broad-spectrum therapeutics against respiratory viruses. Respiratory syncytial virus (RSV) is a major threat to pediatric patients and older adults. We describe 4′-fluorouridine (4′-FlU, EIDD-2749), a ribonucleoside analog that inhibits RSV, related RNA viruses, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with high selectivity index in cells and human airway epithelia organoids. Polymerase inhibition within in vitro RNA-dependent RNA polymerase assays established for RSV and SARS-CoV-2 revealed transcriptional stalling after incorporation. Once-daily oral treatment was highly efficacious at 5 milligrams per kilogram (mg/kg) in RSV-infected mice or 20 mg/kg in ferrets infected with different SARS-CoV-2 variants of concern, initiated 24 or 12 hours after infection, respectively. These properties define 4′-FlU as a broad-spectrum candidate for the treatment of RSV, SARS-CoV-2, and related RNA virus infections.
Topics: Administration, Oral; Animals; Antiviral Agents; COVID-19; Cell Line; Coronavirus RNA-Dependent RNA Polymerase; Disease Models, Animal; Female; Ferrets; Humans; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Mononegavirales; RNA-Dependent RNA Polymerase; Respiratory Mucosa; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; SARS-CoV-2; Transcription, Genetic; Uracil Nucleotides; Virus Replication; COVID-19 Drug Treatment
PubMed: 34855509
DOI: 10.1126/science.abj5508 -
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 -
Viruses Dec 2018The order harbors numerous viruses of significant relevance to human health, including both established and emerging infections. Currently, vaccines are only available... (Review)
Review
The order harbors numerous viruses of significant relevance to human health, including both established and emerging infections. Currently, vaccines are only available for a small subset of these viruses, and antiviral therapies remain limited. Being obligate cellular parasites, viruses must utilize the cellular machinery for their replication and spread. Therefore, targeting cellular pathways used by viruses can provide novel therapeutic approaches. One of the key challenges confronted by both hosts and viruses alike is the successful folding and maturation of proteins. In cells, this task is faced by cellular molecular chaperones, a group of conserved and abundant proteins that oversee protein folding and help maintain protein homeostasis. In this review, we summarize the current knowledge of how the interact with cellular chaperones, highlight key gaps in our knowledge, and discuss the potential of chaperone inhibitors as antivirals.
Topics: Antiviral Agents; HSP70 Heat-Shock Proteins; HSP90 Heat-Shock Proteins; Host-Pathogen Interactions; Humans; Measles virus; Molecular Chaperones; Mononegavirales; Protein Folding; Respiratory Syncytial Viruses; Virus Replication
PubMed: 30544818
DOI: 10.3390/v10120699 -
Clinical Infectious Diseases : An... Jul 2022Respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (hMPV) are increasingly associated with chronic lung allograft dysfunction (CLAD)... (Meta-Analysis)
Meta-Analysis
Respiratory Syncytial Virus, Human Metapneumovirus, and Parainfluenza Virus Infections in Lung Transplant Recipients: A Systematic Review of Outcomes and Treatment Strategies.
BACKGROUND
Respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (hMPV) are increasingly associated with chronic lung allograft dysfunction (CLAD) in lung transplant recipients (LTR). This systematic review primarily aimed to assess outcomes of RSV/PIV/hMPV infections in LTR and secondarily to assess evidence regarding the efficacy of ribavirin.
METHODS
Relevant databases were queried and study outcomes extracted using a standardized method and summarized.
RESULTS
Nineteen retrospective and 12 prospective studies were included (total 1060 cases). Pooled 30-day mortality was low (0-3%), but CLAD progression 180-360 days postinfection was substantial (pooled incidences 19-24%) and probably associated with severe infection. Ribavirin trended toward effectiveness for CLAD prevention in exploratory meta-analysis (odds ratio [OR] 0.61, [0.27-1.18]), although results were highly variable between studies.
CONCLUSIONS
RSV/PIV/hMPV infection was followed by a high CLAD incidence. Treatment options, including ribavirin, are limited. There is an urgent need for high-quality studies to provide better treatment options for these infections.
Topics: Humans; Lung; Metapneumovirus; Parainfluenza Virus 1, Human; Parainfluenza Virus 2, Human; Paramyxoviridae Infections; Prospective Studies; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Retrospective Studies; Ribavirin; Transplant Recipients
PubMed: 35022697
DOI: 10.1093/cid/ciab969 -
Frontiers in Immunology 2022Respiratory tract infections are a leading cause of morbidity and mortality in newborns, infants, and young children. These early life infections present a formidable... (Review)
Review
Respiratory tract infections are a leading cause of morbidity and mortality in newborns, infants, and young children. These early life infections present a formidable immunologic challenge with a number of possibly conflicting goals: simultaneously eliminate the acute pathogen, preserve the primary gas-exchange function of the lung parenchyma in a developing lung, and limit long-term sequelae of both the infection and the inflammatory response. The latter has been most well studied in the context of childhood asthma, where multiple epidemiologic studies have linked early life viral infection with subsequent bronchospasm. This review will focus on the clinical relevance of respiratory syncytial virus (RSV), human metapneumovirus (HMPV), and rhinovirus (RV) and examine the protective and pathogenic host responses within the neonate.
Topics: Child; Child, Preschool; Humans; Immunity; Infant; Infant, Newborn; Metapneumovirus; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Viruses
PubMed: 35493465
DOI: 10.3389/fimmu.2022.863149 -
Uirusu 2012Filoviruses (Ebola and Marburg viruses) cause severe hemorrhagic fever in humans and nonhuman primates. No effective prophylaxis or treatment for filovirus diseases is... (Review)
Review
Filoviruses (Ebola and Marburg viruses) cause severe hemorrhagic fever in humans and nonhuman primates. No effective prophylaxis or treatment for filovirus diseases is yet commercially available. Recent studies have advanced our knowledge of filovirus protein functions and interaction between viral and host factors in the replication cycle. Current findings on the ecology of filoviruses (i.e., natural infection of nonprimate animals and discovery of a new member of filoviruses in Europe) have also provided new insights into the epidemiology of Ebola and Marburg hemorrhagic fever. This article reviews the fundamental aspects of filovirus biology and the latest topics on filovirus research.
Topics: Animals; Cell Adhesion; Drug Discovery; Filoviridae; Filoviridae Infections; Humans; Molecular Targeted Therapy; Viral Proteins; Virion; Virus Replication
PubMed: 24153230
DOI: 10.2222/jsv.62.197