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Chemical Reviews Apr 2018Flaviviruses, such as dengue, Japanese encephalitis, tick-borne encephalitis, West Nile, yellow fever, and Zika viruses, are critically important human pathogens that... (Review)
Review
Flaviviruses, such as dengue, Japanese encephalitis, tick-borne encephalitis, West Nile, yellow fever, and Zika viruses, are critically important human pathogens that sicken a staggeringly high number of humans every year. Most of these pathogens are transmitted by mosquitos, and not surprisingly, as the earth warms and human populations grow and move, their geographic reach is increasing. Flaviviruses are simple RNA-protein machines that carry out protein synthesis, genome replication, and virion packaging in close association with cellular lipid membranes. In this review, we examine the molecular biology of flaviviruses touching on the structure and function of viral components and how these interact with host factors. The latter are functionally divided into pro-viral and antiviral factors, both of which, not surprisingly, include many RNA binding proteins. In the interface between the virus and the hosts we highlight the role of a noncoding RNA produced by flaviviruses to impair antiviral host immune responses. Throughout the review, we highlight areas of intense investigation, or a need for it, and potential targets and tools to consider in the important battle against pathogenic flaviviruses.
Topics: Flavivirus; Genes, Viral; Host-Pathogen Interactions; Humans; RNA-Binding Proteins; Virus Replication
PubMed: 29652486
DOI: 10.1021/acs.chemrev.7b00719 -
MSphere Oct 2023Jingmen tick virus (JMTV), belonging to the family, is a novel segmented RNA virus identified in 2014 in the Jingmen region of Hubei Province, China. Up to now, JMTV... (Review)
Review
Jingmen tick virus (JMTV), belonging to the family, is a novel segmented RNA virus identified in 2014 in the Jingmen region of Hubei Province, China. Up to now, JMTV has been detected in a variety of countries or regions in Asia, Europe, Africa, and the Americas, involving a wide range of arthropods and mammals, and even humans. The JMTV genome is composed of four linear RNA segments, two of which are derived from flaviviruses, while the other two segments are unique to JMTV and has no matching virus. Currently, JMTV has been shown to have a pathogenic effect on humans. Humans who had been infected would develop viremia and variable degrees of clinical symptoms. However, the pathogenic mechanism of JMTV has not been elucidated yet. Therefore, it is crucial to strengthen the epidemiological surveillance and laboratory studies of JMTV.
Topics: Animals; Humans; Arboviruses; Ticks; Flavivirus; Flaviviridae; Europe; Mammals
PubMed: 37702505
DOI: 10.1128/msphere.00281-23 -
FEBS Letters Oct 2017Virus invasion triggers host immune responses, in particular, innate immune responses. Pathogen-associated molecular patterns of viruses (such as dsRNA, ssRNA, or viral... (Review)
Review
Virus invasion triggers host immune responses, in particular, innate immune responses. Pathogen-associated molecular patterns of viruses (such as dsRNA, ssRNA, or viral proteins) released during virus replication are detected by the corresponding pattern-recognition receptors of the host, and innate immune responses are induced. Through production of type-I and type-III interferons as well as various other cytokines, the host innate immune system forms the frontline to protect host cells and inhibit virus infection. Not surprisingly, viruses have evolved diverse strategies to counter this antiviral system. In this review, we discuss the multiple strategies used by proteases of positive-sense single-stranded RNA viruses of the families Picornaviridae, Coronaviridae, and Flaviviridae, when counteracting host innate immune responses.
Topics: Animals; Coronaviridae; Cytokines; Flaviviridae; Gene Expression Regulation; Humans; Immune Evasion; Immunity, Innate; Interferons; Picornaviridae; Protein Structure, Secondary; Signal Transduction; Toll-Like Receptors; Viral Proteins; Virus Diseases; Virus Replication
PubMed: 28850669
DOI: 10.1002/1873-3468.12827 -
Viruses Aug 2022Members of the family are posing a significant threat to human health worldwide. Many flaviviruses are capable of inducing severe inflammation in humans. nonstructural... (Review)
Review
Members of the family are posing a significant threat to human health worldwide. Many flaviviruses are capable of inducing severe inflammation in humans. nonstructural proteins, apart from their canonical roles in viral replication, have noncanonical functions strongly affecting antiviral innate immunity. Among these functions, antagonism of type I IFN is the most investigated; meanwhile, more data are accumulated on their role in the other pathways of innate response. This review systematizes the last known data on the role of nonstructural proteins in molecular mechanisms of triggering inflammation, with an emphasis on their interactions with TLRs and RLRs, interference with NF-κB and cGAS-STING signaling, and activation of inflammasomes.
Topics: Flaviviridae; Humans; Immunity, Innate; Inflammasomes; Inflammation; Signal Transduction
PubMed: 36016430
DOI: 10.3390/v14081808 -
Viruses Sep 2023Classical swine fever virus (CSFV), which is a positive-sense, single-stranded RNA virus with an envelope, is a member of the genus in the family. CSFV causes a severe... (Review)
Review
Classical swine fever virus (CSFV), which is a positive-sense, single-stranded RNA virus with an envelope, is a member of the genus in the family. CSFV causes a severe and highly contagious disease in pigs and is prevalent worldwide, threatening the pig farming industry. The detailed mechanisms of the CSFV life cycle have been reported, but are still limited. Some receptors and attachment factors of CSFV, including heparan sulfate (HS), laminin receptor (LamR), complement regulatory protein (CD46), MER tyrosine kinase (MERTK), disintegrin, and metalloproteinase domain-containing protein 17 (ADAM17), were identified. After attachment, CSFV internalizes via clathrin-mediated endocytosis (CME) and/or caveolae/raft-dependent endocytosis (CavME). After internalization, CSFV moves to early and late endosomes before uncoating. During this period, intracellular trafficking of CSFV relies on components of the endosomal sorting complex required for transport (ESCRT) and Rab proteins in the endosome dynamics, with a dependence on the cytoskeleton network. This review summarizes the data on the mechanisms of CSFV attachment, internalization pathways, and intracellular trafficking, and provides a general view of the early events in the CSFV life cycle.
Topics: Animals; Swine; Classical Swine Fever Virus; Pestivirus; Endocytosis; Classical Swine Fever
PubMed: 37766277
DOI: 10.3390/v15091870 -
Advances in Virus Research 2022Reverse genetics is the prospective analysis of how genotype determines phenotype. In a typical experiment, a researcher alters a viral genome, then observes the...
Reverse genetics is the prospective analysis of how genotype determines phenotype. In a typical experiment, a researcher alters a viral genome, then observes the phenotypic outcome. Among RNA viruses, this approach was first applied to positive-strand RNA viruses in the mid-1970s and over nearly 50 years has become a powerful and widely used approach for dissecting the mechanisms of viral replication and pathogenesis. During this time the global health importance of two virus groups, flaviviruses (genus Flavivirus, family Flaviviridae) and betacoronaviruses (genus Betacoronavirus, subfamily Orthocoronavirinae, family Coronaviridae), have dramatically increased, yet these viruses have genomes that are technically challenging to manipulate. As a result, several new techniques have been developed to overcome these challenges. Here I briefly review key historical aspects of positive-strand RNA virus reverse genetics, describe some recent reverse genetic innovations, particularly as applied to flaviviruses and coronaviruses, and discuss their benefits and limitations within the larger context of rigorous genetic analysis.
Topics: Flavivirus; Genome, Viral; Positive-Strand RNA Viruses; RNA Viruses; Reverse Genetics; Virus Replication
PubMed: 35840179
DOI: 10.1016/bs.aivir.2022.03.001 -
Viruses Oct 2017Flaviviridae-caused diseases are a critical, emerging public health problem worldwide. Flaviviridae infections usually cause severe, acute or chronic diseases, such as... (Review)
Review
Flaviviridae-caused diseases are a critical, emerging public health problem worldwide. Flaviviridae infections usually cause severe, acute or chronic diseases, such as liver damage and liver cancer resulting from a hepatitis C virus (HCV) infection and high fever and shock caused by yellow fever. Many researchers worldwide are investigating the mechanisms by which Flaviviridae cause severe diseases. Flaviviridae can interfere with the host's innate immunity to achieve their purpose of proliferation. For instance, dengue virus (DENV) NS2A, NS2B3, NS4A, NS4B and NS5; HCV NS2, NS3, NS3/4A, NS4B and NS5A; and West Nile virus (WNV) NS1 and NS4B proteins are involved in immune evasion. This review discusses the interplay between viral non-structural Flaviviridae proteins and relevant host proteins, which leads to the suppression of the host's innate antiviral immunity.
Topics: Animals; Antiviral Agents; Flaviviridae; Flaviviridae Infections; Humans; Immune Evasion; Immunity, Innate; Mice; Viral Nonstructural Proteins
PubMed: 28991176
DOI: 10.3390/v9100291 -
Methods (San Diego, Calif.) Dec 2015Establishment of in vitro systems to study mechanisms of RNA synthesis for positive strand RNA viruses have been very useful in the past and have shed light on the... (Review)
Review
Establishment of in vitro systems to study mechanisms of RNA synthesis for positive strand RNA viruses have been very useful in the past and have shed light on the composition of protein and RNA components, optimum conditions, the nature of the products formed, cis-acting RNA elements and trans-acting protein factors required for efficient synthesis. In this review, we summarize our current understanding regarding the requirements for flavivirus RNA synthesis in vitro. We describe details of reaction conditions, the specificity of template used by either the multi-component membrane-bound viral replicase complex or by purified, recombinant RNA-dependent RNA polymerase. We also discuss future perspectives to extend the boundaries of our knowledge.
Topics: Flavivirus; Nucleic Acid Amplification Techniques; RNA, Viral; RNA-Dependent RNA Polymerase
PubMed: 26272247
DOI: 10.1016/j.ymeth.2015.08.002 -
Annual Review of Virology Sep 2016Hepaciviruses and pegiviruses constitute two closely related sister genera of the family Flaviviridae. In the past five years, the known phylogenetic diversity of the... (Review)
Review
Hepaciviruses and pegiviruses constitute two closely related sister genera of the family Flaviviridae. In the past five years, the known phylogenetic diversity of the hepacivirus genera has absolutely exploded. What was once an isolated infection in humans (and possibly other primates) has now expanded to include horses, rodents, bats, colobus monkeys, cows, and, most recently, catsharks, shedding new light on the genetic diversity and host range of hepaciviruses. Interestingly, despite the identification of these many animal and primate hepaciviruses, the equine hepaciviruses remain the closest genetic relatives of the human hepaciviruses, providing an intriguing clue to the zoonotic source of hepatitis C virus. This review summarizes the significance of these studies and discusses current thinking about the origin and evolution of the animal hepaciviruses as well as their potential usage as surrogate models for the study of hepatitis C virus.
Topics: Animals; Cattle; Chiroptera; Colobus; Flavivirus; GB virus A; GB virus C; Genetic Variation; Genome, Viral; Hepacivirus; Hepatitis C; Horses; Host Specificity; Humans; Pestivirus; Sharks
PubMed: 27741408
DOI: 10.1146/annurev-virology-100114-055104 -
Viruses Mar 2019Bats are known to harbor and transmit many emerging and re-emerging viruses, many of which are extremely pathogenic in humans but do not cause overt pathology in their... (Review)
Review
Bats are known to harbor and transmit many emerging and re-emerging viruses, many of which are extremely pathogenic in humans but do not cause overt pathology in their bat reservoir hosts: henipaviruses (Nipah and Hendra), filoviruses (Ebola and Marburg), and coronaviruses (SARS-CoV and MERS-CoV). Direct transmission cycles are often implicated in these outbreaks, with virus shed in bat feces, urine, and saliva. An additional mode of virus transmission between bats and humans requiring further exploration is the spread of disease via arthropod vectors. Despite the shared ecological niches that bats fill with many hematophagous arthropods (e.g. mosquitoes, ticks, biting midges, etc.) known to play a role in the transmission of medically important arboviruses, knowledge surrounding the potential for bats to act as reservoirs for arboviruses is limited. To this end, a comprehensive literature review was undertaken examining the current understanding and potential for bats to act as reservoirs for viruses transmitted by blood-feeding arthropods. Serosurveillance and viral isolation from either free-ranging or captive bats are described in relation to four arboviral groups (, , , ). Further, ecological associations between bats and hematophagous viral vectors are characterized (e.g. bat bloodmeals in mosquitoes, ingestion of mosquitoes by bats, etc). Lastly, knowledge gaps related to hematophagous ectoparasites (bat bugs and bed bugs () and bat flies ( and )), in addition to future directions for characterization of bat-vector-virus relationships are described.
Topics: Animals; Arboviruses; Arthropod Vectors; Chiroptera; Dengue Virus; Diptera; Disease Reservoirs; Mosquito Vectors; West Nile virus; Zika Virus; Zoonoses
PubMed: 30832426
DOI: 10.3390/v11030215