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The Journal of Infectious Diseases Oct 2023The Paramyxoviridae family includes established human pathogens such as measles virus, mumps virus, and the human parainfluenza viruses; highly lethal zoonotic pathogens... (Review)
Review
The Paramyxoviridae family includes established human pathogens such as measles virus, mumps virus, and the human parainfluenza viruses; highly lethal zoonotic pathogens such as Nipah virus; and a number of recently identified agents, such as Sosuga virus, which remain poorly understood. The high human-to-human transmission rate of paramyxoviruses such as measles virus, high case fatality rate associated with other family members such as Nipah virus, and the existence of poorly characterized zoonotic pathogens raise concern that known and unknown paramyxoviruses have significant pandemic potential. In this review, the general life cycle, taxonomic relationships, and viral pathogenesis are described for paramyxoviruses that cause both systemic and respiratory system-restricted infections. Next, key gaps in critical areas are presented, following detailed conversations with subject matter experts and based on the current literature. Finally, we present an assessment of potential prototype pathogen candidates that could be used as models to study this important virus family, including assessment of the strengths and weaknesses of each potential prototype.
Topics: Humans; Pandemics; Paramyxoviridae; Nipah Virus; Vaccines; Antiviral Agents
PubMed: 37849400
DOI: 10.1093/infdis/jiad123 -
Viruses Jan 2020Paramyxovirus (PMV) entry requires the coordinated action of two envelope glycoproteins, the receptor binding protein (RBP) and fusion protein (F). The sequence of... (Review)
Review
Paramyxovirus (PMV) entry requires the coordinated action of two envelope glycoproteins, the receptor binding protein (RBP) and fusion protein (F). The sequence of events that occurs during the PMV entry process is tightly regulated. This regulation ensures entry will only initiate when the virion is in the vicinity of a target cell membrane. Here, we review recent structural and mechanistic studies to delineate the entry features that are shared and distinct amongst the . In general, we observe overarching distinctions between the protein-using RBPs and the sialic acid- (SA-) using RBPs, including how their stalk domains differentially trigger F. Moreover, through sequence comparisons, we identify greater structural and functional conservation amongst the PMV fusion proteins, as compared to the RBPs. When examining the relative contributions to sequence conservation of the globular head versus stalk domains of the RBP, we observe that, for the protein-using PMVs, the stalk domains exhibit higher conservation and find the opposite trend is true for SA-using PMVs. A better understanding of conserved and distinct features that govern the entry of protein-using versus SA-using PMVs will inform the rational design of broader spectrum therapeutics that impede this process.
Topics: Carrier Proteins; Humans; N-Acetylneuraminic Acid; Paramyxoviridae; Protein Binding; Viral Fusion Proteins; Virus Attachment; Virus Internalization
PubMed: 32019182
DOI: 10.3390/v12020161 -
Nature Feb 2024An ideal vaccine both attenuates virus growth and disease in infected individuals and reduces the spread of infections in the population, thereby generating herd...
An ideal vaccine both attenuates virus growth and disease in infected individuals and reduces the spread of infections in the population, thereby generating herd immunity. Although this strategy has proved successful by generating humoral immunity to measles, yellow fever and polio, many respiratory viruses evolve to evade pre-existing antibodies. One approach for improving the breadth of antiviral immunity against escape variants is through the generation of memory T cells in the respiratory tract, which are positioned to respond rapidly to respiratory virus infections. However, it is unknown whether memory T cells alone can effectively surveil the respiratory tract to the extent that they eliminate or greatly reduce viral transmission following exposure of an individual to infection. Here we use a mouse model of natural parainfluenza virus transmission to quantify the extent to which memory CD8 T cells resident in the respiratory tract can provide herd immunity by reducing both the susceptibility of acquiring infection and the extent of transmission, even in the absence of virus-specific antibodies. We demonstrate that protection by resident memory CD8 T cells requires the antiviral cytokine interferon-γ (IFNγ) and leads to altered transcriptional programming of epithelial cells within the respiratory tract. These results suggest that tissue-resident CD8 T cells in the respiratory tract can have important roles in protecting the host against viral disease and limiting viral spread throughout the population.
Topics: Animals; Mice; CD8-Positive T-Lymphocytes; Disease Models, Animal; Epithelial Cells; Immunity, Herd; Immunologic Memory; Interferon-gamma; Memory T Cells; Paramyxoviridae; Paramyxoviridae Infections; Respiratory System; Transcription, Genetic; Humans
PubMed: 38086420
DOI: 10.1038/s41586-023-06937-1 -
Advances in Virus Research 2018Despite the availability of safe and effective vaccines against measles and several animal morbilliviruses, they continue to cause regular outbreaks and epidemics in... (Review)
Review
Despite the availability of safe and effective vaccines against measles and several animal morbilliviruses, they continue to cause regular outbreaks and epidemics in susceptible populations. Morbilliviruses are highly contagious and share a similar pathogenesis in their respective hosts. This review provides an overview of morbillivirus history and the general replication cycle and recapitulates Morbillivirus pathogenesis focusing on common and unique aspects seen in different hosts. It also summarizes the state of knowledge regarding virus-host interactions on the cellular level with an emphasis on viral interference with innate immune response activation, and highlights remaining knowledge gaps.
Topics: Animals; Host-Pathogen Interactions; Humans; Immune Evasion; Morbillivirus; Morbillivirus Infections; Virus Replication
PubMed: 29551144
DOI: 10.1016/bs.aivir.2017.12.003 -
Virus Research Apr 2017The paramyxo- and pneumoviruses are members of the order Mononegavirales, a group of viruses with non-segmented, negative strand RNA genomes. The polymerases of these... (Review)
Review
The paramyxo- and pneumoviruses are members of the order Mononegavirales, a group of viruses with non-segmented, negative strand RNA genomes. The polymerases of these viruses are multi-functional complexes, capable of transcribing subgenomic capped and polyadenylated mRNAs and replicating the genome. Although there is no native structure available for any complete paramyxo- or pneumovirus polymerase, functional and structural studies of a fragment of a pneumovirus polymerase protein and mutation analyses and resistance profiling of small-molecule inhibitors have generated a wealth of mechanistic information. This review integrates these data with the structure of a related polymerase, identifying similarities, differences, gaps in knowledge, and avenues for antiviral drug development.
Topics: DNA Mutational Analysis; Drug Resistance, Viral; Mutation, Missense; Paramyxoviridae; Pneumovirus; RNA-Dependent RNA Polymerase; Transcription, Genetic; Virus Replication
PubMed: 28104450
DOI: 10.1016/j.virusres.2017.01.008 -
Viruses Nov 2019Morbilliviruses are important pathogens, to the point that they have shaped the history of human and animal health [...].
Morbilliviruses are important pathogens, to the point that they have shaped the history of human and animal health [...].
Topics: Animals; Humans; Morbillivirus; Virus Diseases; Virus Internalization; Virus Release; Virus Replication
PubMed: 31703308
DOI: 10.3390/v11111036 -
PLoS Neglected Tropical Diseases Feb 2022In this review, we highlight the risk to livestock and humans from infections with henipaviruses, which belong to the virus family Paramyxoviridae. We provide a... (Review)
Review
In this review, we highlight the risk to livestock and humans from infections with henipaviruses, which belong to the virus family Paramyxoviridae. We provide a comprehensive overview of documented outbreaks of Nipah and Hendra virus infections affecting livestock and humans and assess the burden on the economy and health systems. In an increasingly globalized and interconnected world, attention must be paid to emerging viruses and infectious diseases, as transmission routes can be rapid and worldwide.
Topics: Animals; Communicable Diseases, Emerging; Disease Outbreaks; Hendra Virus; Henipavirus Infections; Humans; Livestock; Nipah Virus; Viral Zoonoses
PubMed: 35180217
DOI: 10.1371/journal.pntd.0010157 -
Viruses Jan 2024Henipaviruses are a genus of emerging pathogens that includes the highly virulent Nipah and Hendra viruses that cause reoccurring outbreaks of disease. Henipaviruses... (Review)
Review
Henipaviruses are a genus of emerging pathogens that includes the highly virulent Nipah and Hendra viruses that cause reoccurring outbreaks of disease. Henipaviruses rely on two surface glycoproteins, known as the attachment and fusion proteins, to facilitate entry into host cells. As new and divergent members of the genus have been discovered and structurally characterized, key differences and similarities have been noted. This review surveys the available structural information on glycoproteins, complementing this with information from related biophysical and structural studies of the broader family of which Henipaviruses are members. The process of viral entry is a primary focus for vaccine and drug development, and this review aims to identify critical knowledge gaps in our understanding of the mechanisms that drive fusion.
Topics: Humans; Henipavirus; Nipah Virus; Henipavirus Infections; Glycoproteins; Hendra Virus
PubMed: 38399971
DOI: 10.3390/v16020195 -
The Lancet. Global Health Aug 2019Influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus are the most common viruses associated with acute lower respiratory infections in...
BACKGROUND
Influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus are the most common viruses associated with acute lower respiratory infections in young children (<5 years) and older people (≥65 years). A global report of the monthly activity of these viruses is needed to inform public health strategies and programmes for their control.
METHODS
In this systematic analysis, we compiled data from a systematic literature review of studies published between Jan 1, 2000, and Dec 31, 2017; online datasets; and unpublished research data. Studies were eligible for inclusion if they reported laboratory-confirmed incidence data of human infection of influenza virus, respiratory syncytial virus, parainfluenza virus, or metapneumovirus, or a combination of these, for at least 12 consecutive months (or 52 weeks equivalent); stable testing practice throughout all years reported; virus results among residents in well-defined geographical locations; and aggregated virus results at least on a monthly basis. Data were extracted through a three-stage process, from which we calculated monthly annual average percentage (AAP) as the relative strength of virus activity. We defined duration of epidemics as the minimum number of months to account for 75% of annual positive samples, with each component month defined as an epidemic month. Furthermore, we modelled monthly AAP of influenza virus and respiratory syncytial virus using site-specific temperature and relative humidity for the prediction of local average epidemic months. We also predicted global epidemic months of influenza virus and respiratory syncytial virus on a 5° by 5° grid. The systematic review in this study is registered with PROSPERO, number CRD42018091628.
FINDINGS
We initally identified 37 335 eligible studies. Of 21 065 studies remaining after exclusion of duplicates, 1081 full-text articles were assessed for eligibility, of which 185 were identified as eligible. We included 246 sites for influenza virus, 183 sites for respiratory syncytial virus, 83 sites for parainfluenza virus, and 65 sites for metapneumovirus. Influenza virus had clear seasonal epidemics in winter months in most temperate sites but timing of epidemics was more variable and less seasonal with decreasing distance from the equator. Unlike influenza virus, respiratory syncytial virus had clear seasonal epidemics in both temperate and tropical regions, starting in late summer months in the tropics of each hemisphere, reaching most temperate sites in winter months. In most temperate sites, influenza virus epidemics occurred later than respiratory syncytial virus (by 0·3 months [95% CI -0·3 to 0·9]) while no clear temporal order was observed in the tropics. Parainfluenza virus epidemics were found mostly in spring and early summer months in each hemisphere. Metapneumovirus epidemics occurred in late winter and spring in most temperate sites but the timing of epidemics was more diverse in the tropics. Influenza virus epidemics had shorter duration (3·8 months [3·6 to 4·0]) in temperate sites and longer duration (5·2 months [4·9 to 5·5]) in the tropics. Duration of epidemics was similar across all sites for respiratory syncytial virus (4·6 months [4·3 to 4·8]), as it was for metapneumovirus (4·8 months [4·4 to 5·1]). By comparison, parainfluenza virus had longer duration of epidemics (6·3 months [6·0 to 6·7]). Our model had good predictability in the average epidemic months of influenza virus in temperate regions and respiratory syncytial virus in both temperate and tropical regions. Through leave-one-out cross validation, the overall prediction error in the onset of epidemics was within 1 month (influenza virus -0·2 months [-0·6 to 0·1]; respiratory syncytial virus 0·1 months [-0·2 to 0·4]).
INTERPRETATION
This study is the first to provide global representations of month-by-month activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus. Our model is helpful in predicting the local onset month of influenza virus and respiratory syncytial virus epidemics. The seasonality information has important implications for health services planning, the timing of respiratory syncytial virus passive prophylaxis, and the strategy of influenza virus and future respiratory syncytial virus vaccination.
FUNDING
European Union Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).
Topics: Female; Global Health; Humans; Influenza A virus; Influenza, Human; Male; Metapneumovirus; Paramyxoviridae Infections; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 31303294
DOI: 10.1016/S2214-109X(19)30264-5 -
The Journal of General Virology Dec 2019The family consists of large enveloped RNA viruses infecting mammals, birds, reptiles and fish. Many paramyxoviruses are host-specific and several, such as measles...
The family consists of large enveloped RNA viruses infecting mammals, birds, reptiles and fish. Many paramyxoviruses are host-specific and several, such as measles virus, mumps virus, Nipah virus, Hendra virus and several parainfluenza viruses, are pathogenic for humans. The transmission of paramyxoviruses is horizontal, mainly through airborne routes; no vectors are known. This is a summary of the current International Committee on Taxonomy of Viruses (ICTV) Report on the family . which is available at ictv.global/report/paramyxoviridae.
Topics: DNA Barcoding, Taxonomic; Databases, Factual; Humans; Paramyxoviridae; Web Browser
PubMed: 31609197
DOI: 10.1099/jgv.0.001328