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Antiviral Research Jul 2019Human parainfluenza viruses cause acute respiratory tract infections and disease predominantly in young children and immunocompromised individuals. Currently, there are... (Review)
Review
Human parainfluenza viruses cause acute respiratory tract infections and disease predominantly in young children and immunocompromised individuals. Currently, there are no vaccines to prevent hPIV infections, nor licensed anti-hPIV drugs. There is therefore a need for specific antiviral therapies to decrease the morbidity and mortality associated with hPIV diseases. Haemagglutinin-neuraminidase (HN) is one of two hPIV surface proteins with critical roles in host receptor recognition, binding and cleavage; it has been explored as a key drug development target for the past few decades with variable success. Recent advancements in computational modelling and the availability of the X-ray crystal structure of hPIV3 HN have improved our understanding of the structural and mechanistic features of HN. This review explores structural features of the HN protein that are being exploited for structure-guided inhibitor design. We describe past and present hPIV HN inhibition strategies based on sialic acid scaffolds, together with other novel approaches that decrease hPIV infectivity. Although many HN inhibitors have been developed and evaluated as anti-hPIV agents, currently only a host-directed therapy (DAS181) has succeeded in phase II clinical drug trials. Hence, the review concludes with future considerations for targeting the specific function(s) of hPIV HN and suggestions for antiviral drug design.
Topics: Antiviral Agents; Child; Child, Preschool; Drug Delivery Systems; Drug Design; Drug Resistance, Viral; Enzyme Inhibitors; Genome, Viral; HN Protein; Humans; Immunocompromised Host; N-Acetylneuraminic Acid; Neuraminidase; Parainfluenza Virus 1, Human; Parainfluenza Virus 3, Human; Paramyxoviridae Infections; Viral Proteins; Virus Internalization
PubMed: 30951732
DOI: 10.1016/j.antiviral.2019.04.001 -
Jornal de Pediatria 2023To identify and assess the current evidence available about the costs of managing hospitalized pediatric patients diagnosed with Respiratory Syncytial Virus (RSV) and... (Review)
Review
OBJECTIVE
To identify and assess the current evidence available about the costs of managing hospitalized pediatric patients diagnosed with Respiratory Syncytial Virus (RSV) and Parainfluenza Virus Type 3 (PIV3) in upper-middle-income countries.
METHODS
The authors conducted a systematic review across seven key databases from database inception to July 2022. Costs extracted were converted into 2022 International Dollars using the Purchasing Power Parity-adjusted. PROSPERO identifier: CRD42020225757.
RESULTS
No eligible study for PIV3 was recovered. For RSV, cost analysis and COI studies were performed for populations in Colombia, China, Malaysia, and Mexico. Comparing the total economic impact, the lowest cost per patient at the pediatric ward was observed in Malaysia ($ 347.60), while the highest was in Colombia ($ 709.66). On the other hand, at pediatric ICU, the lowest cost was observed in China ($ 1068.26), while the highest was in Mexico ($ 3815.56). Although there is no consensus on the major cost driver, all included studies described that the medications (treatment) consumed over 30% of the total cost. A high rate of inappropriate prescription drugs was observed.
CONCLUSION
The present study highlighted how RSV infection represents a substantial economic burden to health care systems and to society. The findings of the included studies suggest a possible association between baseline risk status and expenditures. Moreover, it was observed that an important amount of the cost is destinated to treatments that have no evidence or support in most clinical practice guidelines.
Topics: Humans; Child; Infant; Developing Countries; Financial Stress; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Parainfluenza Virus 3, Human; Hospitalization
PubMed: 37247828
DOI: 10.1016/j.jped.2023.05.003 -
RNA (New York, N.Y.) Mar 2019A primary property of paramyxovirus bipartite promoters is to ensure that their RNA genomes are imprinted with a hexamer phase via their association with nucleoproteins,... (Review)
Review
A primary property of paramyxovirus bipartite promoters is to ensure that their RNA genomes are imprinted with a hexamer phase via their association with nucleoproteins, in part because this phase as well the editing sequence itself controls mRNA editing. The question then arises whether a similar mechanism operates for filoviruses that also contain bipartite promoters that are governed by the "rule of six," even though these genomes need not, and given Ebola virus biology, cannot always be of hexamer genome length. This review suggests that this is possible and describes how it might operate, and that RNA editing may play a role in Ebola virus genome interconversion that helps the virus adapt to different host environments.
Topics: Filoviridae; Gene Expression Regulation, Viral; Genome, Viral; Paramyxoviridae; Promoter Regions, Genetic; RNA Editing; RNA, Viral; Viral Proteins; Virus Replication
PubMed: 30587495
DOI: 10.1261/rna.068825.118 -
Virus Research May 2019Pneumoviruses represent a major public health burden across the world. Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV), two of the most recognizable... (Review)
Review
Pneumoviruses represent a major public health burden across the world. Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV), two of the most recognizable pediatric infectious agents, belong to this family. These viruses are enveloped with a non-segmented negative-sense RNA genome, and their replication occurs in specialized cytosolic organelles named inclusion bodies (IB). The critical role of IBs in replication of pneumoviruses has begun to be elucidated, and our current understanding suggests they are highly dynamic structures. From IBs, newly synthesized nucleocapsids are transported to assembly sites, potentially via the actin cytoskeleton, to be incorporated into nascent virions. Released virions, which generally contain one genome, can then diffuse in the extracellular environment to target new cells and reinitiate the process of infection. This is a challenging business for virions, which must face several risks including the extracellular immune responses. In addition, several recent studies suggest that successful infection may be achieved more rapidly by multiple, rather than single, genomic copies being deposited into a target cell. Interestingly, recent data indicate that pneumoviruses have several mechanisms that permit their transmission en bloc, i.e. transmission of multiple genomes at the same time. These mechanisms include the well-studied syncytia formation as well as the newly described formation of long actin-based intercellular extensions. These not only permit en bloc viral transmission, but also bypass assembly of complete virions. In this review we describe several aspects of en bloc viral transmission and how these mechanisms are reshaping our understanding of pneumovirus replication, assembly and spread.
Topics: Animals; Cell Line; Humans; Metapneumovirus; Mice; Paramyxoviridae Infections; Pneumovirus; RNA, Viral; Virion; Virus Assembly; Virus Replication
PubMed: 30844414
DOI: 10.1016/j.virusres.2019.03.002 -
Methods in Molecular Biology (Clifton,... 2022Human parainfluenza virus types 1 (hPIV-1) and 3 (hPIV-3) belong to the family Paramyxoviridae, subfamily Paramyxoviridae, and genus Respirovirus. The viruses enter by...
Human parainfluenza virus types 1 (hPIV-1) and 3 (hPIV-3) belong to the family Paramyxoviridae, subfamily Paramyxoviridae, and genus Respirovirus. The viruses enter by utilizing glycoproteins or glycosphingolipids (gangliosides) containing sialic acid on the cell membrane. We developed a solid-phase binding assay to evaluate hPIV-1, hPIV-3, and Sendai virus' abilities to bind to different types of gangliosides. hPIV1 and hPIV3 show strong binding to neolacto-series gangliosides containing a non-reducing terminal sialic acid residue and different specificity regarding the sialic acid linkages. This solid-phase binding assay is suitable to evaluate other orthomyxoviruses and paramyxoviruses' binding specificities utilizing sialic acids.
Topics: Biological Assay; Gangliosides; Humans; N-Acetylneuraminic Acid; Respirovirus; Sendai virus
PubMed: 36175635
DOI: 10.1007/978-1-0716-2635-1_14 -
Viruses Oct 2016Morbilliviruses share considerable structural and functional similarities. Even though disease severity varies among the respective host species, the underlying... (Comparative Study)
Comparative Study Review
Morbilliviruses share considerable structural and functional similarities. Even though disease severity varies among the respective host species, the underlying pathogenesis and the clinical signs are comparable. Thus, insights gained with one morbillivirus often apply to the other members of the genus. Since the (CDV) causes severe and often lethal disease in dogs and ferrets, it is an attractive model to characterize morbillivirus pathogenesis mechanisms and to evaluate the efficacy of new prophylactic and therapeutic approaches. This review compares the cellular tropism, pathogenesis, mechanisms of persistence and immunosuppression of the (MeV) and CDV. It then summarizes the contributions made by studies on the CDV in dogs and ferrets to our understanding of MeV pathogenesis and to vaccine and drugs development.
Topics: Animals; Disease Models, Animal; Distemper Virus, Canine; Dogs; Ferrets; Humans; Immune Evasion; Immune Tolerance; Measles virus; Viral Tropism
PubMed: 27727184
DOI: 10.3390/v8100274 -
Viruses Nov 2016The measles virus (MeV) is a contagious pathogenic RNA virus of the family , genus , that can cause serious symptoms and even fetal complications. Here, we summarize... (Review)
Review
The measles virus (MeV) is a contagious pathogenic RNA virus of the family , genus , that can cause serious symptoms and even fetal complications. Here, we summarize current molecular advances in MeV research, and emphasize the connection between host cells and MeV replication. Although measles has reemerged recently, the potential for its eradication is promising with significant progress in our understanding of the molecular mechanisms of its replication and host-pathogen interactions.
Topics: Host-Pathogen Interactions; Humans; Immunity, Innate; Measles virus; Virus Replication
PubMed: 27854326
DOI: 10.3390/v8110308 -
Comparative Immunology, Microbiology... Aug 2016The genus Morbillivirus is classified into the family Paramyxoviridae, and is composed of 6 members, namely measles virus (MV), rinderpest virus (RPV),... (Review)
Review
The genus Morbillivirus is classified into the family Paramyxoviridae, and is composed of 6 members, namely measles virus (MV), rinderpest virus (RPV), peste-des-petits-ruminants virus (PPRV), canine distemper virus (CDV), phocine distemper virus (PDV) and cetacean morbillivirus (CeMV). The MV, RPV, PPRV and CDV have been successfully attenuated through their serial passages in vitro for the production of live vaccines. It has been demonstrated that the morbilliviral virulence in animals was progressively attenuated with their consecutive passages in vitro. However, only a few reports were involved in explanation of an attenuation-related mechanism on them until many years after the establishment of a quasispecies theory. RNA virus quasispecies arise from rapid evolution of viruses with high mutation rate during genomic replication, and play an important role in gradual loss of viral virulence by serial passages. Here, we overviewed the development of live-attenuated vaccine strains against morbilliviruses by consecutive passages in vitro, and further discussed a related mechanism concerning the relationship between virulence attenuation and viral evolution.
Topics: Animals; Cattle; Evolution, Molecular; Genetic Fitness; Genome, Viral; Morbillivirus; Mutation; Serial Passage; Vaccines, Attenuated; Viral Vaccines; Virulence
PubMed: 27477502
DOI: 10.1016/j.cimid.2016.05.007 -
Viruses Dec 2021Pneumoviruses include pathogenic human and animal viruses, the most known and studied being the human respiratory syncytial virus (hRSV) and the metapneumovirus (hMPV),... (Review)
Review
Pneumoviruses include pathogenic human and animal viruses, the most known and studied being the human respiratory syncytial virus (hRSV) and the metapneumovirus (hMPV), which are the major cause of severe acute respiratory tract illness in young children worldwide, and main pathogens infecting elderly and immune-compromised people. The transcription and replication of these viruses take place in specific cytoplasmic inclusions called inclusion bodies (IBs). These activities depend on viral polymerase L, associated with its cofactor phosphoprotein P, for the recognition of the viral RNA genome encapsidated by the nucleoprotein N, forming the nucleocapsid (NC). The polymerase activities rely on diverse transient protein-protein interactions orchestrated by P playing the hub role. Among these interactions, P interacts with the NC to recruit L to the genome. The P protein also plays the role of chaperone to maintain the neosynthesized N monomeric and RNA-free (called N) before specific encapsidation of the viral genome and antigenome. This review aims at giving an overview of recent structural information obtained for hRSV and hMPV P, N, and more specifically for P-NC and N-P complexes that pave the way for the rational design of new antivirals against those viruses.
Topics: Animals; Antiviral Agents; Drug Design; Humans; Metapneumovirus; Models, Molecular; Nucleocapsid Proteins; Paramyxoviridae Infections; Phosphoproteins; Protein Binding; Protein Conformation; RNA, Viral; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Transcription, Genetic; Viral Proteins; Virus Replication
PubMed: 34960719
DOI: 10.3390/v13122449 -
Viruses Oct 2019Canine distemper virus (CDV) and phocine distemper (PDV) are closely-related members of the family, genus , in the order . CDV has a broad host range among carnivores.... (Review)
Review
Canine distemper virus (CDV) and phocine distemper (PDV) are closely-related members of the family, genus , in the order . CDV has a broad host range among carnivores. PDV is thought to be derived from CDV through contact between terrestrial carnivores and seals. PDV has caused extensive mortality in Atlantic seals and other marine mammals, and more recently has spread to the North Pacific Ocean. CDV also infects marine carnivores, and there is evidence of infection of seals and other species in Antarctica. Recently, CDV has spread to felines and other wildlife species in the Serengeti and South Africa. Some CDV vaccines may also have caused wildlife disease. Changes in the virus haemagglutinin (H) protein, particularly the signaling lymphocyte activation molecule (SLAM) receptor binding site, correlate with adaptation to non-canine hosts. Differences in the phosphoprotein (P) gene sequences between disease and non-disease causing CDV strains may relate to pathogenicity in domestic dogs and wildlife. Of most concern are reports of CDV infection and disease in non-human primates raising the possibility of zoonosis. In this article we review the global occurrence of CDV and PDV, and present both historical and genetic information relating to these viruses crossing species barriers.
Topics: Animals; Animals, Wild; Cats; Cetacea; Climate Change; Distemper Virus, Canine; Distemper Virus, Phocine; Dogs; Host Specificity; Morbillivirus; Morbillivirus Infections; Pets; Primates; Viral Proteins
PubMed: 31615092
DOI: 10.3390/v11100944