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Current Opinion in Immunology Aug 2022Viral proteins fold into a variety of structures as they perform their functions. Structure-based vaccine design aims to exploit knowledge of an antigen's architecture... (Review)
Review
Viral proteins fold into a variety of structures as they perform their functions. Structure-based vaccine design aims to exploit knowledge of an antigen's architecture to stabilize it in a vulnerable conformation. We summarize the general principles of structure-based vaccine design, with a focus on the major types of sequence modifications: proline, disulfide, cavity-filling, electrostatic and hydrogen-bond substitution, as well as domain deletion. We then review recent applications of these principles to vaccine-design efforts across five viral families: Coronaviridae, Orthomyxoviridae, Paramyxoviridae, Pneumoviridae, and Filoviridae. Outstanding challenges include continued application of proven design principles to pathogens of interest, as well as development of new strategies for those pathogens that resist traditional techniques.
Topics: Coronaviridae; Filoviridae; Humans; Orthomyxoviridae; Paramyxoviridae; Pneumovirinae; Vaccine Development; Viral Proteins; Viral Vaccines
PubMed: 35598506
DOI: 10.1016/j.coi.2022.102209 -
Current Opinion in Pulmonary Medicine May 2012The first era in the discoveries of respiratory viruses occured between 1933 and 1965 when influenza virus, enteroviruses, adenovirus, respiratory syncytial virus,... (Review)
Review
PURPOSE OF REVIEW
The first era in the discoveries of respiratory viruses occured between 1933 and 1965 when influenza virus, enteroviruses, adenovirus, respiratory syncytial virus, rhinovirus, parainfluenza virus and coronavirus (CoV) were found by virus culture. In the 1990s, the development of high throughput viral detection and diagnostics instruments increased diagnostic sensitivity and enabled the search for new viruses. This article briefly reviews the clinical significance of newly discovered respiratory viruses.
RECENT FINDINGS
In 2001, the second era in the discoveries of respiratory viruses began, and several new respiratory viruses and their subgroups have been found: human metapneumovirus, CoVs NL63 and HKU1, human bocavirus and human rhinovirus C and D groups.
SUMMARY
Currently, a viral cause of pediatric respiratory illness is identifiable in up to 95% of cases, but the detection rates decrease steadily by age, to 30-40% in the elderly. The new viruses cause respiratory illnesses such as common cold, bronchitis, bronchiolitis, exacerbations of asthma and chronic obstructive pulmonary disease and pneumonia. Rarely, acute respiratory failure may occur. The clinical role of other new viruses, KI and WU polyomaviruses and the torque teno virus, as respiratory pathogens is not clear.
Topics: Bocavirus; Coronavirus; Humans; Metapneumovirus; Pneumonia, Viral; Polyomavirus; Respiratory Syncytial Viruses; Respiratory Tract Infections; Reverse Transcriptase Polymerase Chain Reaction; Rhinovirus; Torque teno virus
PubMed: 22366993
DOI: 10.1097/MCP.0b013e328351f8d4 -
Uirusu Dec 2006Human metapneumovirus (hMPV), first isolated in the Netherlands in 2001, is a member of the genus Metapneumovirus of the sub-family Pneumovirinae of the family... (Review)
Review
Human metapneumovirus (hMPV), first isolated in the Netherlands in 2001, is a member of the genus Metapneumovirus of the sub-family Pneumovirinae of the family Paramyxoviridae. The genomic organization of hMPV is 3'-N-P-M-F-M2-SH-G-L-5'. hMPV resembles the sole member of this genus, avian pneumovirus. hMPV is the most closely related human pathogen to respiratory syncytial virus. Phylogenetic analysis of the nucleotide sequences indicated that there were two genetic groups. Furthermore, each group could be subdivided into two subgroups. hMPV encodes three surface proteins, F, G and SH proteins. The majority of antibodies to hMPV in serum were antibody against F protein, which mediates cross-group neutralization and protection. The incidences of hMPV-associated respiratory infection estimate 5 to 10% in children and 2 to 4% in adults. hMPV generally causes upper respiratory tract infection and flu-like illness, the virus can be associated with lower tract infections, such as wheezy bronchitis, bronchitis, bronchiolitis and pneumonia, in very young children, elderly persons, and immunocompromised patients. hMPV has a seasonal peak during the spring in Japan. Reinfection with hMPV frequently occurs in children, implying that the host immune response induced by natural infection provides incomplete protection. The RT-PCR test is the most sensitive test for detection of hMPV.
Topics: Adult; Aged; Aged, 80 and over; Animals; Child; Disease Outbreaks; Humans; Infant; Metapneumovirus; Paramyxoviridae Infections; RNA, Viral; Respiratory Tract Infections; Reverse Transcriptase Polymerase Chain Reaction; Seasons
PubMed: 17446666
DOI: 10.2222/jsv.56.173 -
Viruses Jan 2013Human metapneumovirus (HMPV) is a relative newly described virus. It was first isolated in 2001 and currently appears to be one of the most significant and common human... (Review)
Review
Human metapneumovirus (HMPV) is a relative newly described virus. It was first isolated in 2001 and currently appears to be one of the most significant and common human viral infections. Retrospective serologic studies demonstrated the presence of HMPV antibodies in humans more than 50 years earlier. Although the virus was primarily known as causative agent of respiratory tract infections in children, HMPV is an important cause of respiratory infections in adults as well. Almost all children are infected by HMPV below the age of five; the repeated infections throughout life indicate transient immunity. HMPV infections usually are mild and self-limiting, but in the frail elderly and the immunocompromised patients, the clinical course can be complicated. Since culturing the virus is relatively difficult, diagnosis is mostly based on a nucleic acid amplification test, such as reverse transcriptase polymerase chain reaction. To date, no vaccine is available and treatment is supportive. However, ongoing research shows encouraging results. The aim of this paper is to review the current literature concerning HMPV infections in adults, and discuss recent development in treatment and vaccination.
Topics: Adult; Animals; Humans; Metapneumovirus; Paramyxoviridae Infections; Respiratory Tract Infections
PubMed: 23299785
DOI: 10.3390/v5010087 -
Pneumologie (Stuttgart, Germany) Jun 2020RSV induces an acute viral disease with involvement of the respiratory tract. It can be notably life-threatening for infants but also for older adults. New RSV-subtypes... (Review)
Review
RSV induces an acute viral disease with involvement of the respiratory tract. It can be notably life-threatening for infants but also for older adults. New RSV-subtypes are constantly evolving globally. The knowledge about epidemiology, hygiene measures, diagnostics and clinical feature is essential not only for the paediatrician. Vaccines or specific therapeutics are still missing. This article gives an overview with focus on RSV in adults. In addition, molecular pathological characteristics of the virus are explained, research approaches concerning vaccines and therapeutics are mentioned and current problems in management are discussed.
Topics: Humans; Respiratory Insufficiency; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 32557509
DOI: 10.1055/a-0853-2881 -
Journal of Virological Methods Nov 2015Paramyxovirus entry into cells requires fusion of the viral and cell membranes mediated by one of the major virus glycoproteins, the fusion (F) glycoprotein which...
Paramyxovirus entry into cells requires fusion of the viral and cell membranes mediated by one of the major virus glycoproteins, the fusion (F) glycoprotein which transits from a metastable pre-fusion conformation to a highly stable post-fusion structure during the membrane fusion process. F protein refolding involves large conformational changes of the protein trimer. One of these changes results in assembly of two heptad repeat sequences (HRA and HRB) from each protomer into a six-helix bundle (6HB) motif. To assist in distinguishing pre- and post-fusion conformations of the Pneumovirinae F proteins, and as extension of previous work (Palomo et al., 2014), a general strategy was designed to obtain polyclonal and particularly monoclonal antibodies specific of the 6HB motif of the Pneumovirinae fusion protein. The antibodies reported here should assist in the characterization of the structural changes that the F protein of human metapneumovirus or respiratory syncytial virus experiences during the process of membrane fusion.
Topics: Animals; Antibodies, Monoclonal; Antibodies, Viral; Female; Mice, Inbred BALB C; Pneumovirinae; Protein Conformation; Rabbits; Viral Fusion Proteins
PubMed: 26275682
DOI: 10.1016/j.jviromet.2015.08.002 -
Viral Immunology Mar 2018Human parainfluenza viruses (family Paramyxoviridae), human metapneumovirus, and respiratory syncytial virus (family Pneumoviridae) infect most infants and children... (Review)
Review
Human parainfluenza viruses (family Paramyxoviridae), human metapneumovirus, and respiratory syncytial virus (family Pneumoviridae) infect most infants and children within the first few years of life and are the etiologic agents for many serious acute respiratory illnesses. These virus infections are also associated with long-term diseases that impact quality of life, including asthma. Despite over a half-century of vaccine research, development, and clinical trials, no vaccine has been licensed to date for the paramyxoviruses or pneumoviruses for the youngest infants. In this study, we describe the recent reclassification of paramyxoviruses and pneumoviruses into distinct families by the International Committee on the Taxonomy of Viruses. We also discuss some past unsuccessful vaccine trials and some currently preferred vaccine strategies. Finally, we discuss hurdles that must be overcome to support successful respiratory virus vaccine development for the youngest children.
Topics: Animals; Clinical Trials as Topic; Drug Discovery; Drug Evaluation, Preclinical; Humans; Paramyxoviridae Infections; Paramyxovirinae; Pneumovirinae; Respiratory Syncytial Virus Infections; Viral Vaccines
PubMed: 29323621
DOI: 10.1089/vim.2017.0137 -
Virulence 2014Globally, the human respiratory syncytial virus (hRSV) is the major cause of lower respiratory tract infections (LRTIs) in infants and children younger than 2 years old.... (Review)
Review
Globally, the human respiratory syncytial virus (hRSV) is the major cause of lower respiratory tract infections (LRTIs) in infants and children younger than 2 years old. Furthermore, the number of hospitalizations due to LRTIs has shown a sustained increase every year due to the lack of effective vaccines against hRSV. Thus, this virus remains as a major public health and economic burden worldwide. The lung pathology developed in hRSV-infected humans is characterized by an exacerbated inflammatory and Th2 immune response. In order to rationally design new vaccines and therapies against this virus, several studies have focused in elucidating the interactions between hRSV virulence factors and the host immune system. Here, we discuss the main features of hRSV biology, the processes involved in virus recognition by the immune system and the most relevant mechanisms used by this pathogen to avoid the antiviral host response.
Topics: Adaptive Immunity; Child; Child, Preschool; Genome, Viral; Humans; Immune Evasion; Immunity, Innate; Infant; Lymphocyte Activation; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Viral Proteins; Virulence Factors
PubMed: 25513775
DOI: 10.4161/viru.32225 -
Clinical Microbiology Reviews Jul 2006Since the discovery of human metapneumovirus (hMPV) in 2001, the virus has been identified worldwide. hMPV is a common respiratory pathogen, particularly in infants and... (Review)
Review
Since the discovery of human metapneumovirus (hMPV) in 2001, the virus has been identified worldwide. hMPV is a common respiratory pathogen, particularly in infants and young children. The virus is associated with both upper and lower respiratory tract infections and may be a trigger for asthma. At least two major genotypes of hMPV circulate during community outbreaks. Whether these genotypes represent distinct serotypes remains controversial. The major challenges faced by the medical and scientific communities are the understanding of the pathogenesis of hMPV disease and the development of a safe and effective vaccine to protect against infection and disease caused by this newly recognized respiratory virus.
Topics: Child, Preschool; Humans; Metapneumovirus; Molecular Epidemiology; Paramyxoviridae Infections; Respiratory Tract Infections; Seasons
PubMed: 16847085
DOI: 10.1128/CMR.00014-06 -
Annals of the New York Academy of... Apr 2007Pneumovirus infection remains a significant problem for both human and veterinary medicine. Both avian pneumovirus (aMPV, Turkey rhinotracheitis virus) and human... (Review)
Review
Pneumovirus infection remains a significant problem for both human and veterinary medicine. Both avian pneumovirus (aMPV, Turkey rhinotracheitis virus) and human metapneumovirus (hMPV) are pathogens of birds and humans, which are associated with respiratory tract infections. Based on their different genomic organization and low level of nucleotide (nt) and amino acid (aa) identity with paramyxoviruses in the genus Pneumovirus, aMPV and hMPV have been classified into a new genus referred to as Metapneumovirus. The advancement of our understanding of pneumovirus biology and pathogenesis of pneumovirus disease in specific natural hosts can provide us with strategies for vaccine formulations and combined antiviral and immunomodulatory therapies.
Topics: Animals; Bird Diseases; Birds; Genome, Viral; Humans; Metapneumovirus; Paramyxoviridae Infections; Respiratory Tract Infections; Viral Proteins; Virus Internalization
PubMed: 17470912
DOI: 10.1196/annals.1408.005