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Viruses Dec 2020The paramyxo- and pneumovirus family includes a wide range of viruses that can cause respiratory and/or systemic infections in humans and animals. The significant... (Review)
Review
The paramyxo- and pneumovirus family includes a wide range of viruses that can cause respiratory and/or systemic infections in humans and animals. The significant disease burden of these viruses is further exacerbated by the limited therapeutics that are currently available. Host cellular proteins that can antagonize or limit virus replication are therefore a promising area of research to identify candidate molecules with the potential for host-targeted therapies. Host proteins known as host cell restriction factors are constitutively expressed and/or induced in response to virus infection and include proteins from interferon-stimulated genes (ISGs). Many ISG proteins have been identified but relatively few have been characterized in detail and most studies have focused on studying their antiviral activities against particular viruses, such as influenza A viruses and human immunodeficiency virus (HIV)-1. This review summarizes current literature regarding host cell restriction factors against paramyxo- and pneumoviruses, on which there is more limited data. Alongside discussion of known restriction factors, this review also considers viral countermeasures in overcoming host restriction, the strengths and limitations in different experimental approaches in studies reported to date, and the challenges in reconciling differences between in vitro and in vivo data. Furthermore, this review provides an outlook regarding the landscape of emerging technologies and tools available to study host cell restriction factors, as well as the suitability of these proteins as targets for broad-spectrum antiviral therapeutics.
Topics: Animals; Biomarkers; Gene Expression Regulation, Viral; Host Specificity; Host-Pathogen Interactions; Humans; Immunity, Innate; Paramyxoviridae Infections; Paramyxovirinae; Pneumovirus; Pneumovirus Infections; Viral Tropism; Virus Replication
PubMed: 33276587
DOI: 10.3390/v12121381 -
Neurotherapeutics : the Journal of the... Apr 2017Malignant glioma is the most common primary brain tumor and carries a grim prognosis, with a median survival of just over 14 months. Given the poor outcomes with... (Review)
Review
Malignant glioma is the most common primary brain tumor and carries a grim prognosis, with a median survival of just over 14 months. Given the poor outcomes with standard-of-care treatments, novel treatment strategies are needed. The concept of virotherapy for the treatment of malignant tumors dates back more than a century and can be divided into replication-competent oncolytic viruses and replication-deficient viral vectors. Oncolytic viruses are designed to selectively target, infect, and replicate in tumor cells, while sparing surrounding normal brain. A host of oncolytic viruses has been evaluated in early phase human trials with promising safety results, but none has progressed to phase III trials. Despite the 25 years that has passed since the initial publication of genetically engineered oncolytic viruses for the treatment of glioma, much remains to be learned about the use of this therapy, including its mechanism of action, optimal treatment paradigm, appropriate targets, and integration with adjuvant agents. Oncolytic viral therapy for glioma remains promising and will undoubtedly impact the future of patient care.
Topics: Adenoviridae; Animals; Brain Neoplasms; Clinical Trials as Topic; Genetic Vectors; Glioma; Humans; Oncolytic Virotherapy; Oncolytic Viruses; Paramyxoviridae; Parvovirus; Poliovirus; Reoviridae; Treatment Outcome; Virus Replication
PubMed: 28265902
DOI: 10.1007/s13311-017-0516-0 -
Global genetic diversity of measles virus (Paramyxoviridae: ): historical aspects and current state.Voprosy Virusologii Nov 2023Monitoring the circulation of the measles virus and studying its genetic diversity is an important component of the measles elimination program. A methodological... (Review)
Review
Monitoring the circulation of the measles virus and studying its genetic diversity is an important component of the measles elimination program. A methodological approach to molecular genetic studies and their interpretation in the measles surveillance was developed in the early 2000s. During its development, clear areas of circulation of each genotype of the virus were identified, therefore, the determination of viruses' genotypes was proposed to monitor circulation and identify transmission pathways. However, in the future, due to a significant decrease in the number of active genotypes, an approach based on sub-genotyping was proposed: determining not only the genotype of the virus, but also its genetic lineage/genetic variant. The Global Measles and Rubella Laboratory Network (GMRLN) systematically monitors the circulation of the measles virus at the sub-genotypic level, depositing the results in a specialized database MeaNS2. It is this database that is the most complete and reliable source of information about the genetic characteristic of measles viruses. This review presents both historical information and the latest data on the global genetic diversity of the measles virus.
Topics: Humans; Measles virus; Morbillivirus; Paramyxoviridae; Molecular Epidemiology; Measles; Genotype; Genetic Variation
PubMed: 38156571
DOI: 10.36233/0507-4088-187 -
Clinical Microbiology Reviews Oct 2016Globally, as a leading agent of acute respiratory tract infections in children <5 years of age and the elderly, the human metapneumovirus (HMPV) has gained considerable... (Review)
Review
Globally, as a leading agent of acute respiratory tract infections in children <5 years of age and the elderly, the human metapneumovirus (HMPV) has gained considerable attention. As inferred from studies comparing vaccinated and experimentally infected mice, the acquired immune response elicited by this pathogen fails to efficiently clear the virus from the airways, which leads to an exaggerated inflammatory response and lung damage. Furthermore, after disease resolution, there is a poor development of T and B cell immunological memory, which is believed to promote reinfections and viral spread in the community. In this article, we discuss the molecular mechanisms that shape the interactions of HMPV with host tissues that lead to pulmonary pathology and to the development of adaptive immunity that fails to protect against natural infections by this virus.
Topics: Adaptive Immunity; Animals; Disease Models, Animal; Host-Pathogen Interactions; Humans; Metapneumovirus; Mice; Paramyxoviridae Infections; Respiratory Tract Infections
PubMed: 27413096
DOI: 10.1128/CMR.00081-15 -
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 -
Mediators of Inflammation 2016Neurotropic viruses can cause devastating central nervous system (CNS) infections, especially in young children and the elderly. The blood-brain barrier (BBB) and the... (Review)
Review
Neurotropic viruses can cause devastating central nervous system (CNS) infections, especially in young children and the elderly. The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) have been described as relevant sites of entry for specific viruses as well as for leukocytes, which are recruited during the proinflammatory response in the course of CNS infection. In this review, we illustrate examples of established brain barrier models, in which the specific reaction patterns of different viral families can be analyzed. Furthermore, we highlight the pathogen specific array of cytokines and chemokines involved in immunological responses in viral CNS infections. We discuss in detail the link between specific cytokines and chemokines and leukocyte migration profiles. The thorough understanding of the complex and interrelated inflammatory mechanisms as well as identifying universal mediators promoting CNS inflammation is essential for the development of new diagnostic and treatment strategies.
Topics: Animals; Blood-Brain Barrier; Cell Movement; Central Nervous System Infections; Chemokines; Cytokines; Flaviviridae; Herpesviridae; Humans; Inflammation; Leukocytes; Paramyxoviridae; Picornaviridae; Retroviridae; Togaviridae; Virus Diseases; Viruses
PubMed: 27313404
DOI: 10.1155/2016/8562805 -
Viruses Dec 2014We review the molecular and epidemiological characteristics of cetacean morbillivirus (CeMV) and the diagnosis and pathogenesis of associated disease, with six different... (Review)
Review
We review the molecular and epidemiological characteristics of cetacean morbillivirus (CeMV) and the diagnosis and pathogenesis of associated disease, with six different strains detected in cetaceans worldwide. CeMV has caused epidemics with high mortality in odontocetes in Europe, the USA and Australia. It represents a distinct species within the Morbillivirus genus. Although most CeMV strains are phylogenetically closely related, recent data indicate that morbilliviruses recovered from Indo-Pacific bottlenose dolphins (Tursiops aduncus), from Western Australia, and a Guiana dolphin (Sotalia guianensis), from Brazil, are divergent. The signaling lymphocyte activation molecule (SLAM) cell receptor for CeMV has been characterized in cetaceans. It shares higher amino acid identity with the ruminant SLAM than with the receptors of carnivores or humans, reflecting the evolutionary history of these mammalian taxa. In Delphinidae, three amino acid substitutions may result in a higher affinity for the virus. Infection is diagnosed by histology, immunohistochemistry, virus isolation, RT-PCR, and serology. Classical CeMV-associated lesions include bronchointerstitial pneumonia, encephalitis, syncytia, and lymphoid depletion associated with immunosuppression. Cetaceans that survive the acute disease may develop fatal secondary infections and chronic encephalitis. Endemically infected, gregarious odontocetes probably serve as reservoirs and vectors. Transmission likely occurs through the inhalation of aerosolized virus but mother to fetus transmission was also reported.
Topics: Animals; Cetacea; Morbillivirus; Morbillivirus Infections; Phylogeny
PubMed: 25533660
DOI: 10.3390/v6125145 -
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 -
Viruses May 2020Feline morbillivirus (FeMV) was first isolated in stray cats in Hong Kong in 2012. Since its discovery, the virus has been reported in domestic cats worldwide, including... (Review)
Review
Feline morbillivirus (FeMV) was first isolated in stray cats in Hong Kong in 2012. Since its discovery, the virus has been reported in domestic cats worldwide, including in Hong Kong, Japan, Italy, US, Brazil, Turkey, UK, Germany, and Malaysia. FeMV is classified in the genus within the family. FeMV research has focused primarily on determining the host range, symptoms, and characteristics of persistent infections in vitro. Importantly, there is a potential association between FeMV infection and feline kidney diseases, such as tubulointerstitial nephritis (TIN) and chronic kidney diseases (CKD), which are known to significantly affect feline health and survival. However, the tropism and viral entry mechanism(s) of FeMV remain unknown. In this review, we summarize the FeMV studies up to date, including the discoveries of various FeMV strains, basic virology, pathogenicity, and disease signs.
Topics: Animals; Cat Diseases; Cats; Kidney Diseases; Morbillivirus; Morbillivirus Infections; Paramyxoviridae
PubMed: 32370044
DOI: 10.3390/v12050501