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Immunology Letters Jun 2008Pneumonia virus of mice (PVM; family Paramyxoviridae, genus Pneumovirus) is a natural mouse pathogen that is closely related to human and bovine respiratory syncytial... (Review)
Review
Pneumonia virus of mice (PVM; family Paramyxoviridae, genus Pneumovirus) is a natural mouse pathogen that is closely related to human and bovine respiratory syncytial viruses. Among the prominent features of this infection, robust replication of PVM takes place in bronchial epithelial cells in response to a minimal virus inoculum. Virus replication in situ results in local production of proinflammatory cytokines (MIP-1alpha, MIP-2, MCP-1 and IFNgamma) and granulocyte recruitment to the lung. If left unchecked, PVM infection and the ensuing inflammatory response ultimately lead to pulmonary edema, respiratory compromise and death. In this review, we consider the recent studies using the PVM model that have provided important insights into the role of the inflammatory response in the pathogenesis of severe respiratory virus infection. We also highlight several works that have elucidated acquired immune responses to this pathogen, including T cell responses and the development of humoral immunity. Finally, we consider several immunomodulatory strategies that have been used successfully to reduce morbidity and mortality when administered to PVM-infected, symptomatic mice, and thus hold promise as realistic therapeutic strategies for severe respiratory virus infections in human subjects.
Topics: Animals; Genome, Viral; Humans; Hypersensitivity; Mice; Pneumovirus; Pneumovirus Infections; Respiratory Tract Infections; T-Lymphocytes
PubMed: 18471897
DOI: 10.1016/j.imlet.2008.03.013 -
Viral Immunology 2021The resolution revolution of cryo-electron microscopy (cryo-EM) has made a significant impact on the structural analysis of the multifunctional RNA polymerases. In...
The resolution revolution of cryo-electron microscopy (cryo-EM) has made a significant impact on the structural analysis of the multifunctional RNA polymerases. In recent months, several high-resolution structures of RNA polymerases of , which includes the human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV), have been determined by single-particle cryo-EM. These structures illustrated high similarities and minor differences between the polymerases and revealed the potential mechanisms of the RNA synthesis.
Topics: Cryoelectron Microscopy; DNA-Directed RNA Polymerases; Humans; Pneumovirus; Respiratory Syncytial Virus, Human
PubMed: 32429800
DOI: 10.1089/vim.2020.0018 -
Current Medicinal Chemistry 2012Respiratory syncytial virus (RSV; Family Paramyxoviridae, Genus Pneumovirus) is a major respiratory pathogen of infants and children and an emerging pathogen of the... (Review)
Review
Respiratory syncytial virus (RSV; Family Paramyxoviridae, Genus Pneumovirus) is a major respiratory pathogen of infants and children and an emerging pathogen of the elderly. Current management of RSV disease includes monoclonal antibody prophylaxis for infants identified as high risk and supportive care for those with active infection; there is no vaccine, although several are under study. In this manuscript, we review published findings from human autopsy studies, as well as experiments that focus on human clinical samples and mouse models of acute pneumovirus infection that elucidate basic principles of disease pathogenesis. Consideration of these data suggests that the inflammatory responses to RSV and related pneumoviral pathogens can be strong, persistent, and beyond the control of conventional antiviral and anti-inflammatory therapies, and can have profound negative consequences to the host. From this perspective, we consider the case for specific immunomodulatory strategies that may have the potential to alleviate some of the more serious sequelae of this disease.
Topics: Animals; Antibodies, Monoclonal; Antiviral Agents; Cytokines; Disease Models, Animal; Humans; Immunologic Factors; Oligodeoxyribonucleotides, Antisense; Pneumovirus; Pneumovirus Infections; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 22360479
DOI: 10.2174/092986712799828346 -
Viruses May 2020Respiratory syncytial virus (RSV) is often the first clinically relevant pathogen encountered in life, with nearly all children infected by two years of age. Many... (Review)
Review
Respiratory syncytial virus (RSV) is often the first clinically relevant pathogen encountered in life, with nearly all children infected by two years of age. Many studies have also linked early-life severe respiratory viral infection with more pathogenic immune responses later in life that lead to pulmonary diseases like childhood asthma. This phenomenon is thought to occur through long-term immune system alterations following early-life respiratory viral infection and may include local responses such as unresolved inflammation and/or direct structural or developmental modifications within the lung. Furthermore, systemic responses that could impact the bone marrow progenitors may be a significant cause of long-term alterations, through inflammatory mediators and shifts in metabolic profiles. Among these alterations may be changes in transcriptional and epigenetic programs that drive persistent modifications throughout life, leaving the immune system poised toward pathogenic responses upon secondary insult. This review will focus on early-life severe RSV infection and long-term alterations. Understanding these mechanisms will not only lead to better treatment options to limit initial RSV infection severity but also protect against the development of childhood asthma linked to severe respiratory viral infections.
Topics: Adaptive Immunity; Animals; Epigenomics; Humans; Lung; Lung Diseases; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 32375305
DOI: 10.3390/v12050505 -
Virus Genes Dec 2022Respiratory syncytial virus (RSV) causes lower respiratory tract infections and bronchiolitis, mainly affecting children under 2 years of age and immunocompromised... (Review)
Review
Respiratory syncytial virus (RSV) causes lower respiratory tract infections and bronchiolitis, mainly affecting children under 2 years of age and immunocompromised patients. Currently, there are no available vaccines or efficient pharmacological treatments against RSV. In recent years, tremendous efforts have been directed to understand the pathological mechanisms of the disease and generate a vaccine against RSV. Although RSV is highly infectious, not all the patients who get infected develop bronchiolitis and severe disease. Through various sequencing studies, single nucleotide polymorphisms (SNPs) have been discovered in diverse receptors, cytokines, and transcriptional regulators with crucial role in the activation of the innate immune response, which is implicated in the susceptibility to develop or protect from severe forms of the infection. In this review, we highlighted how variations in the key genes affect the development of innate immune response against RSV. This data would provide crucial information about the mechanisms of viral infection, and in the future, could help in generation of new strategies for vaccine development or generation of the pharmacological treatments.
Topics: Child; Humans; Infant; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Immunity, Innate; Bronchiolitis; Polymorphism, Single Nucleotide; Respiratory Syncytial Virus, Human
PubMed: 36085536
DOI: 10.1007/s11262-022-01932-6 -
Clinical Microbiology Reviews Oct 2008To explain the wide spectrum of disease severity caused by respiratory syncytial virus (RSV) and because of the limitations of animal models to fully parallel human RSV... (Review)
Review
To explain the wide spectrum of disease severity caused by respiratory syncytial virus (RSV) and because of the limitations of animal models to fully parallel human RSV disease, study of genetic influences on human RSV disease severity has begun. Candidate gene approaches have demonstrated associations of severe RSV in healthy infants with genetic polymorphisms that may alter the innate ability of humans to control RSV (surfactants, Toll-like receptor 4, cell surface adhesion molecules, and others) and those that may control differences in proinflammatory responses or enhanced immunopathology (specific cytokines and their receptors). These studies are reviewed. They are valuable since an understanding of the direction of a polymorphism's effect can help construct a meaningful human RSV disease pathogenesis model. However, the direction, degree, and significance of the statistical association for any given gene are equivocal among studies, and the functional significance of specific polymorphisms is often not even known. Polymorphism frequency distribution differences associated with RSV infection arising from diversity in the genetic background of the population may be confounded further by multiple-hypothesis testing and publication bias, as well as the investigator's perceived importance of a particular pathogenic disease process. Such problems highlight the limitation of the candidate gene approach and the need for an unbiased large-scale genome-wide association study to evaluate this important disease.
Topics: Disease Susceptibility; Humans; Polymorphism, Genetic; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses
PubMed: 18854487
DOI: 10.1128/CMR.00017-08 -
Viruses Jan 2019The 2nd Symposium of the Canadian Society for Virology (CSV2018) was held in June 2018 in Halifax, Nova Scotia, Canada, as a featured event marking the 200th anniversary...
The 2nd Symposium of the Canadian Society for Virology (CSV2018) was held in June 2018 in Halifax, Nova Scotia, Canada, as a featured event marking the 200th anniversary of Dalhousie University. CSV2018 attracted 175 attendees from across Canada and around the world, more than double the number that attended the first CSV symposium two years earlier. CSV2018 provided a forum to discuss a wide range of topics in virology including human, veterinary, plant, and microbial pathogens. Invited keynote speakers included David Kelvin (Dalhousie University and Shantou University Medical College) who provided a historical perspective on influenza on the 100th anniversary of the 1918 pandemic; Sylvain Moineau (Université Laval) who described CRISPR-Cas systems and anti-CRISPR proteins in warfare between bacteriophages and their host microbes; and Kate O'Brien (then from Johns Hopkins University, now relocated to the World Health Organization where she is Director of Immunization, Vaccines and Biologicals), who discussed the underlying viral etiology for pneumonia in the developing world, and the evidence for respiratory syncytial virus (RSV) as a primary cause. Reflecting a strong commitment of Canadian virologists to science communication, CSV2018 featured the launch of Halifax's first annual Soapbox Science event to enable public engagement with female scientists, and the live-taping of the 499th episode of the This Week in Virology (TWIV) podcast, hosted by Vincent Racaniello (Columbia University) and science writer Alan Dove. TWIV featured interviews of CSV co-founders Nathalie Grandvaux (Université de Montréal) and Craig McCormick (Dalhousie University), who discussed the origins and objectives of the new society; Ryan Noyce (University of Alberta), who discussed technical and ethical considerations of synthetic virology; and Kate O'Brien, who discussed vaccines and global health. Finally, because CSV seeks to provide a better future for the next generation of Canadian virologists, the symposium featured a large number of oral and poster presentations from trainees and closed with the awarding of presentation prizes to trainees, followed by a tour of the Halifax Citadel National Historic Site and an evening of entertainment at the historic Alexander Keith's Brewery.
Topics: Awards and Prizes; Canada; Clustered Regularly Interspaced Short Palindromic Repeats; Congresses as Topic; Influenza Vaccines; Respiratory Syncytial Viruses; Virology
PubMed: 30669273
DOI: 10.3390/v11010079 -
Clinical Infectious Diseases : An... May 2010Currently, only 2 drugs have been approved for the treatment of respiratory syncytial virus (RSV). Palivizumab is a monoclonal antibody for the prevention of RSV in... (Review)
Review
Currently, only 2 drugs have been approved for the treatment of respiratory syncytial virus (RSV). Palivizumab is a monoclonal antibody for the prevention of RSV in high-risk children. Ribavirin is approved for treatment of severe RSV disease; however, its effectiveness in improving outcomes is questionable. During the past 40 years, many obstacles have delayed the development of safe and effective vaccines and treatment regimens. This article reviews these obstacles and presents the novel development strategies used to overcome many of them. Also discussed are promising new antiviral treatment candidates and their associated mechanism of action, the significant advances made in vaccine development, and exciting, new studies directed at improving outcomes through pharmacologic manipulation of the host response to RSV disease.
Topics: Antiviral Agents; Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human
PubMed: 20235830
DOI: 10.1086/651603 -
Poultry Science Jun 2003Respiratory tract diseases are the single most important cause of economic loss due to infections among poultry populations worldwide. However, the molecular mechanisms... (Review)
Review
Respiratory tract diseases are the single most important cause of economic loss due to infections among poultry populations worldwide. However, the molecular mechanisms of the host response to infections remain unknown. Here, we review the literature and describe the adoption of a conceptually simple approach to understand the genetic and biochemical responses of host cells during infection with respiratory pathogens, such as avian pneumovirus (APV). The strategy that we have adopted integrates the powerful techniques of cDNA subtraction hybridization and microarray analysis for global transcriptional profiling. The results of our investigations identify the specific transcriptional alterations in host-cell gene expression that result from an attempt by the host to combat and limit the spread of the pathogen or by the pathogen to enhance its own survival and ability to reproduce. Our studies suggest that a molecular description of host-pathogen interactions in terms of differential gene expression will provide key insights on the molecular basis of disease pathogenesis, pathogen virulence, and host immunity. In addition, the results suggest that the identification of genes and pathways with a role in host response to infection has considerable practical implications for the future design and development of effective immunomodulators and vaccines.
Topics: Animals; DNA, Complementary; Gene Expression Regulation; In Situ Hybridization; Oligonucleotide Array Sequence Analysis; Pneumovirus; Pneumovirus Infections; Poultry; Poultry Diseases; Respiratory Tract Diseases; Transcription, Genetic; Virulence
PubMed: 12817442
DOI: 10.1093/ps/82.6.885 -
American Journal of Respiratory and... Sep 2020
Topics: Chemokines; Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses
PubMed: 32645278
DOI: 10.1164/rccm.202006-2154ED