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Viruses Jun 2014RNA viruses are capable of rapid spread and severe or potentially lethal disease in both animals and humans. The development of reverse genetics systems for... (Review)
Review
RNA viruses are capable of rapid spread and severe or potentially lethal disease in both animals and humans. The development of reverse genetics systems for manipulation and study of RNA virus genomes has provided platforms for designing and optimizing viral mutants for vaccine development. Here, we review the impact of RNA virus reverse genetics systems on past and current efforts to design effective and safe viral therapeutics and vaccines.
Topics: Animals; Coronaviridae; Flaviviridae; Genetic Engineering; Genome, Viral; Humans; Orthomyxoviridae; Paramyxoviridae; RNA Virus Infections; Reverse Genetics; Viral Vaccines
PubMed: 24967693
DOI: 10.3390/v6072531 -
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 -
MBio Jul 2013Paramyxoviruses include major pathogens with significant global health and economic impact. This large family of enveloped RNA viruses infects cells by employing two... (Review)
Review
Paramyxoviruses include major pathogens with significant global health and economic impact. This large family of enveloped RNA viruses infects cells by employing two surface glycoproteins that tightly cooperate to fuse their lipid envelopes with the target cell plasma membrane, an attachment and a fusion (F) protein. Membrane fusion is believed to depend on receptor-induced conformational changes within the attachment protein that lead to the activation and subsequent refolding of F. While structural and mechanistic studies have considerably advanced our insight into paramyxovirus cell adhesion and the structural basis of F refolding, how precisely the attachment protein links receptor engagement to F triggering remained poorly understood. Recent reports based on work with several paramyxovirus family members have transformed our understanding of the triggering mechanism of the membrane fusion machinery. Here, we review these recent findings, which (i) offer a broader mechanistic understanding of the paramyxovirus cell entry system, (ii) illuminate key similarities and differences between entry strategies of different paramyxovirus family members, and (iii) suggest new strategies for the development of novel therapeutics.
Topics: Animals; Humans; Models, Biological; Models, Molecular; Paramyxoviridae; Protein Conformation; Viral Envelope Proteins; Virus Internalization
PubMed: 23820396
DOI: 10.1128/mBio.00413-13 -
Journal of Microbiology, Immunology,... Apr 2015Minigenomes (MGs) are complementary DNAs of the synthetic analogs of genomic RNA. MGs are widely used to study the life cycle of the Paramyxoviridae family of viruses.... (Review)
Review
Minigenomes (MGs) are complementary DNAs of the synthetic analogs of genomic RNA. MGs are widely used to study the life cycle of the Paramyxoviridae family of viruses. MG-based studies have provided valuable insights into the mechanisms of viral replication and transcription in this family, including the roles of viral proteins, the location and boundaries of the cis-acting elements, the functional domains of trans-acting proteins, techniques for the measurement of neutralizing antibody, virus-host interactions, and the structure and function of viral RNA. This article provides a brief overview of the principle and application of MG technology in studies involving members of the Paramyxoviridae family. The advantages, potential limitations, and future scope of MG technology are also discussed.
Topics: Genome, Viral; Host-Pathogen Interactions; Molecular Biology; Paramyxoviridae; Virology; Virus Physiological Phenomena
PubMed: 24767419
DOI: 10.1016/j.jmii.2014.02.008 -
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 -
Journal of Virology Sep 2021We have developed a flexible platform for delivery of proteins to target cell interiors using paramyxovirus-like particles. The key enabling feature is an appendage, 15...
We have developed a flexible platform for delivery of proteins to target cell interiors using paramyxovirus-like particles. The key enabling feature is an appendage, 15 to 30 amino acid residues in length, that is added to cargo proteins and that induces them to bind to the viral matrix (M) protein during virus-like particle (VLP) assembly. The cargo is then incorporated within the VLPs as they bud, using the same interactions that normally direct viral genome packaging. The appendage can also serve as an epitope tag for cargo detection using a nucleocapsid (NP) protein-specific monoclonal antibody. Using this approach, we generated luciferase-loaded VLPs, green fluorescent protein-loaded VLPs, superoxide dismutase-loaded VLPs, and Cre recombinase-loaded VLPs. In each case, the VLPs could efficiently deliver their functional cargos to target cells and, in the case of Cre recombinase, to target cell nuclei. The strategy was employed using two different VLP production platforms, one based on parainfluenza virus 5 (PIV5) and the other based on Nipah virus, and in both cases efficient cargo packaging and delivery could be achieved. These findings provide a foundation for development of paramyxovirus-like particles as tools for safe and efficient delivery of therapeutic proteins to cells and tissues. Therapeutic proteins including transcription factors and genome editors have enormous clinical potential but are currently limited in part due to the challenges of safely and efficiently delivering these proteins to the interiors of target cells. Here, we have developed a new strategy for protein delivery based on manipulation of paramyxovirus genome packaging interactions.
Topics: Drug Delivery Systems; Genetic Engineering; Humans; Luciferases, Renilla; Nucleocapsid; Paramyxoviridae; Viral Matrix Proteins; Virion; Virus Assembly
PubMed: 34379508
DOI: 10.1128/JVI.01030-21 -
Progress in Molecular Biology and... 2015The Paramyxoviridae family includes many viruses that are pathogenic in humans, including parainfluenza viruses, measles virus, respiratory syncytial virus, and the... (Review)
Review
The Paramyxoviridae family includes many viruses that are pathogenic in humans, including parainfluenza viruses, measles virus, respiratory syncytial virus, and the emerging zoonotic Henipaviruses. No effective treatments are currently available for these viruses, and there is a need for efficient antiviral therapies. Paramyxoviruses enter the target cell by binding to a cell surface receptor and then fusing the viral envelope with the target cell membrane, allowing the release of the viral genome into the cytoplasm. Blockage of these crucial steps prevents infection and disease. Binding and fusion are driven by two virus-encoded glycoproteins, the receptor-binding protein and the fusion protein, that together form the viral "fusion machinery." The development of efficient antiviral drugs requires a deeper understanding of the mechanism of action of the Paramyxoviridae fusion machinery, which is still controversial. Here, we review recent structural and functional data on these proteins and the current understanding of the mechanism of the paramyxovirus cell entry process.
Topics: Animals; Glycoproteins; Humans; Paramyxoviridae; Protein Binding; Receptors, Cell Surface; Viral Proteins; Virus Internalization
PubMed: 25595799
DOI: 10.1016/bs.pmbts.2014.10.001 -
Expert Reviews in Molecular Medicine Feb 2011In recent years, several paramyxoviruses have emerged to infect humans, including previously unidentified zoonoses. Hendra and Nipah viruses (henipaviruses within this... (Review)
Review
In recent years, several paramyxoviruses have emerged to infect humans, including previously unidentified zoonoses. Hendra and Nipah viruses (henipaviruses within this family) were first identified in the 1990s in Australia, Malaysia and Singapore, causing epidemics with high mortality and morbidity rates in affected animals and humans. Other paramyxoviruses, such as Menangle virus, Tioman virus, human metapneumovirus and avian paramyxovirus 1, which cause less morbidity in humans, have also been recently identified. Although the Paramyxoviridae family of viruses has been previously recognised as biomedically and veterinarily important, the recent emergence of these paramyxoviruses has focused our attention on this family. Antiviral drugs can be designed to target specific important determinants of the viral life cycle. Therefore, identifying and understanding the mechanistic underpinnings of viral entry, replication, assembly and budding will be critical in the development of antiviral therapeutic agents. This review focuses on the molecular mechanisms discovered and the antiviral strategies pursued in recent years for emerging paramyxoviruses, with particular emphasis on viral entry and exit mechanisms.
Topics: Animals; Antiviral Agents; Drug Delivery Systems; Henipavirus Infections; Humans; Paramyxoviridae; Phylogeny; Virus Attachment
PubMed: 21345285
DOI: 10.1017/S1462399410001754 -
Releve Epidemiologique Hebdomadaire Sep 2002
Topics: Disease Outbreaks; Female; Humans; Incidence; Infectious Disease Transmission, Patient-to-Professional; Malaysia; Male; Paramyxoviridae; Paramyxoviridae Infections; Risk Factors
PubMed: 12238317
DOI: No ID Found -
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