-
Virus Research Jul 2023Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic virus that can cause severe viral encephalitis. Initial interactions between JEV and host cells are... (Review)
Review
Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic virus that can cause severe viral encephalitis. Initial interactions between JEV and host cells are required for productive viral infection and initiation of the viral life cycle. The elucidation of these interactions is critical, not only to understand the pathogenesis of JEV infection, but also to design efficient antiviral strategies. In this review, we outline the known viral and cellular components involved in JEV entry into host cells, with a particular focus on the initial virus-host cell interaction on the cell surface and the downstream early events such as endocytosis, membrane fusion, and viral genome release.
Topics: Animals; Humans; Encephalitis Virus, Japanese; Host Microbial Interactions; Virus Internalization; Encephalitis, Japanese; Endocytosis; Encephalitis Viruses, Japanese; Virus Replication
PubMed: 37086856
DOI: 10.1016/j.virusres.2023.199120 -
The Journal of Veterinary Medical... Mar 2019Tick-borne encephalitis virus (TBEV), a member of the genus Flavivirus within the family Flaviviridae, causes fatal encephalitis with severe sequelae in humans. TBEV is... (Review)
Review
Tick-borne encephalitis virus (TBEV), a member of the genus Flavivirus within the family Flaviviridae, causes fatal encephalitis with severe sequelae in humans. TBEV is prevalent over a wide area of the Eurasian continent including Europe, Russia, Far-Eastern Asia, and Japan. While it was previously thought that TBEV was not endemic in Japan, the first confirmed case of serologically diagnosed TBE was reported in 1993 in the southern area of Hokkaido Prefecture, Japan. In addition, TBEV has been isolated from dogs, wild rodents and ticks in the area. Our epizootiological survey indicated that endemic foci of TBEV were maintained in Hokkaido and other areas of Honshu. TBEV can be divided into three subtypes based on phylogenetic analyses. The Japanese isolates were classified as the Far Eastern subtype, which causes severe neural disorders with a higher mortality rate up to 30%. However, how viral replication and pathogenicity contribute to the neurological manifestations remains unclear. Recent studies have revealed distinctive mechanisms of TBEV pathogenicity and viral genetic factors associated with virulence. This review discusses the recent findings regarding the epidemiology and pathogenesis of TBEV.
Topics: Animals; Encephalitis Viruses, Tick-Borne; Encephalitis, Tick-Borne; Humans; Japan
PubMed: 30674746
DOI: 10.1292/jvms.18-0373 -
Viruses Nov 2022The Japanese encephalitis virus (JEV) is the most common cause of neurodegenerative disease in Southeast Asia and the Western Pacific region; approximately 1.15 billion... (Review)
Review
The Japanese encephalitis virus (JEV) is the most common cause of neurodegenerative disease in Southeast Asia and the Western Pacific region; approximately 1.15 billion people are at risk, and thousands suffer from permanent neurological disorders across Asian countries, with 10-15 thousand people dying each year. JEV crosses the blood-brain barrier (BBB) and forms a complex with receptors on the surface of neurons. GRP78, Src, TLR7, caveolin-1, and dopamine receptor D2 are involved in JEV binding and entry into the neurons, and these receptors also play a role in carcinogenic activity in cells. JEV binds to GRP78, a member of the HSP70 overexpressed on malignant cells to enter neurons, indicating a higher chance of JEV infection in cancer patients. However, JEV enters human brain microvascular endothelial cells via an endocytic pathway mediated by caveolae and the ezrin protein and also targets dopamine-rich areas for infection of the midbrain via altering dopamine levels. In addition, JEV complexed with CLEC5A receptor of macrophage cells is involved in the breakdown of the BBB and central nervous system (CNS) inflammation. CLEC5A-mediated infection is also responsible for the influx of cytokines into the CNS. In this review, we discuss the neuronal and macrophage surface receptors involved in neuronal death.
Topics: Humans; Encephalitis Virus, Japanese; Endothelial Cells; Endoplasmic Reticulum Chaperone BiP; Dopamine; Neurodegenerative Diseases; Encephalitis, Japanese; Central Nervous System; Encephalitis Viruses, Japanese; Receptors, Cell Surface; Lectins, C-Type
PubMed: 36560690
DOI: 10.3390/v14122686 -
Viruses Sep 2022The beginning decades of the 21st century have been marked by multiple emergence and re-emergence phenomena of viral diseases [...].
The beginning decades of the 21st century have been marked by multiple emergence and re-emergence phenomena of viral diseases [...].
Topics: Humans; Encephalitis Viruses, Tick-Borne; West Nile Fever; West Nile virus; Encephalitis, Tick-Borne; Antibodies, Viral
PubMed: 36298675
DOI: 10.3390/v14102120 -
Viruses Jun 2018Tick-borne encephalitis virus (TBEV) is a growing health concern. It causes a severe disease that can lead to permanent neurological complications or death and the... (Review)
Review
Tick-borne encephalitis virus (TBEV) is a growing health concern. It causes a severe disease that can lead to permanent neurological complications or death and the incidence of TBEV infections is constantly rising. Our understanding of TBEV’s structure lags behind that of other flaviviruses, but has advanced recently with the publication of a high-resolution structure of the TBEV virion. The gaps in our knowledge include: aspects of receptor binding, replication and virus assembly. Furthermore, TBEV has mostly been studied in mammalian systems, even though the virus’ interaction with its tick hosts is a central part of its life cycle. Elucidating these aspects of TBEV biology are crucial for the development of TBEV antivirals, as well as the improvement of diagnostics. In this review, we summarise the current structural knowledge on TBEV, bringing attention to the current gaps in our understanding, and propose further research that is needed to truly understand the structural-functional relationship of the virus and its hosts.
Topics: Animals; Encephalitis Viruses, Tick-Borne; Encephalitis, Tick-Borne; Genome, Viral; Genomics; Humans; Life Cycle Stages; Structure-Activity Relationship; Viral Proteins; Virus Replication
PubMed: 29958443
DOI: 10.3390/v10070350 -
Viruses Oct 2022In the last three decades, several flaviviruses of concern that belong to different antigenic groups have expanded geographically. This has resulted in the presence of... (Review)
Review
In the last three decades, several flaviviruses of concern that belong to different antigenic groups have expanded geographically. This has resulted in the presence of often more than one virus from a single antigenic group in some areas, while in Europe, Africa and Australia, additionally, multiple viruses belonging to the Japanese encephalitis (JE) serogroup co-circulate. Morphological heterogeneity of flaviviruses dictates antibody recognition and affects virus neutralization, which influences infection control. The latter is further impacted by sequential infections involving diverse flaviviruses co-circulating within a region and their cross-reactivity. The ensuing complex molecular virus-host interplay leads to either cross-protection or disease enhancement; however, the molecular determinants and mechanisms driving these outcomes are unclear. In this review, we provide an overview of the epidemiology of four JE serocomplex viruses, parameters affecting flaviviral heterogeneity and antibody recognition, host immune responses and the current knowledge of the cross-reactivity involving JE serocomplex flaviviruses that leads to differential clinical outcomes, which may inform future preventative and therapeutic interventions.
Topics: Humans; Encephalitis Viruses, Japanese; Encephalitis, Japanese; Flavivirus; Cross Reactions; Europe; Encephalitis Virus, Japanese; Antibodies, Viral; West Nile virus
PubMed: 36298768
DOI: 10.3390/v14102213 -
Viruses Apr 2022Tick-borne encephalitis virus (TBEV) is a pathogenic, enveloped, positive-stranded RNA virus in the family . Structural studies of flavivirus virions have primarily...
Tick-borne encephalitis virus (TBEV) is a pathogenic, enveloped, positive-stranded RNA virus in the family . Structural studies of flavivirus virions have primarily focused on mosquito-borne species, with only one cryo-electron microscopy (cryo-EM) structure of a tick-borne species published. Here, we present a 3.3 Å cryo-EM structure of the TBEV virion of the Kuutsalo-14 isolate, confirming the overall organisation of the virus. We observe conformational switching of the peripheral and transmembrane helices of M protein, which can explain the quasi-equivalent packing of the viral proteins and highlights their importance in stabilising membrane protein arrangement in the virion. The residues responsible for M protein interactions are highly conserved in TBEV but not in the structurally studied Hypr strain, nor in mosquito-borne flaviviruses. These interactions may compensate for the lower number of hydrogen bonds between E proteins in TBEV compared to the mosquito-borne flaviviruses. The structure reveals two lipids bound in the E protein which are important for virus assembly. The lipid pockets are comparable to those recently described in mosquito-borne Zika, Spondweni, Dengue, and Usutu viruses. Our results thus advance the understanding of tick-borne flavivirus architecture and virion-stabilising interactions.
Topics: Animals; Cryoelectron Microscopy; Culicidae; Encephalitis Viruses, Tick-Borne; Encephalitis, Tick-Borne; Viral Proteins; Virion; Zika Virus; Zika Virus Infection
PubMed: 35458522
DOI: 10.3390/v14040792 -
Journal of Neuroinflammation Sep 2023Flaviviruses are arthropod-borne RNA viruses found worldwide that, when introduced into the human body, cause diseases, including neuroinfections, that can lead to... (Review)
Review
Flaviviruses are arthropod-borne RNA viruses found worldwide that, when introduced into the human body, cause diseases, including neuroinfections, that can lead to serious metabolic consequences and even death. Some of the diseases caused by flaviviruses occur continuously in certain regions, while others occur intermittently or sporadically, causing epidemics. Some of the most common flaviviruses are West Nile virus, dengue virus, tick-borne encephalitis virus, Zika virus and Japanese encephalitis virus. Since all the above-mentioned viruses are capable of penetrating the blood-brain barrier through different mechanisms, their actions also affect the central nervous system (CNS). Like other viruses, flaviviruses, after entering the human body, contribute to redox imbalance and, consequently, to oxidative stress, which promotes inflammation in skin cells, in the blood and in CNS. This review focuses on discussing the effects of oxidative stress and inflammation resulting from pathogen invasion on the metabolic antiviral response of the host, and the ability of viruses to evade the consequences of metabolic changes or exploit them for increased replication and further progression of infection, which affects the development of sequelae and difficulties in therapy.
Topics: Humans; Flavivirus; West Nile virus; Encephalitis Virus, Japanese; Zika Virus; Encephalitis Viruses, Tick-Borne; Inflammation; Central Nervous System Infections; Zika Virus Infection
PubMed: 37775774
DOI: 10.1186/s12974-023-02898-4 -
Viruses Sep 2017Venezuelan equine encephalitis virus (VEEV) is a New World alphavirus that is vectored by mosquitos and cycled in rodents. It can cause disease in equines and humans... (Review)
Review
Venezuelan equine encephalitis virus (VEEV) is a New World alphavirus that is vectored by mosquitos and cycled in rodents. It can cause disease in equines and humans characterized by a febrile illness that may progress into encephalitis. Like the capsid protein of other viruses, VEEV capsid is an abundant structural protein that binds to the viral RNA and interacts with the membrane-bound glycoproteins. It also has protease activity, allowing cleavage of itself from the growing structural polypeptide during translation. However, VEEV capsid protein has additional nonstructural roles within the host cell functioning as the primary virulence factor for VEEV. VEEV capsid inhibits host transcription and blocks nuclear import in mammalian cells, at least partially due to its complexing with the host CRM1 and importin α/β1 nuclear transport proteins. VEEV capsid also shuttles between the nucleus and cytoplasm and is susceptible to inhibitors of nuclear trafficking, making it a promising antiviral target. Herein, the role of VEEV capsid in viral replication and pathogenesis will be discussed including a comparison to proteins of other alphaviruses.
Topics: Active Transport, Cell Nucleus; Animals; Capsid; Capsid Proteins; Cell Line; Encephalitis Virus, Eastern Equine; Encephalitis Virus, Venezuelan Equine; Encephalitis Virus, Western Equine; Horses; Humans; Karyopherins; Nucleocytoplasmic Transport Proteins; RNA, Viral; Receptors, Cytoplasmic and Nuclear; Virulence Factors; Virus Replication; Exportin 1 Protein
PubMed: 28961161
DOI: 10.3390/v9100279 -
Frontiers in Immunology 2023The genus contains a wide variety of viruses that cause severe disease in humans, including dengue virus, yellow fever virus, Zika virus, West Nile virus, Japanese... (Review)
Review
The genus contains a wide variety of viruses that cause severe disease in humans, including dengue virus, yellow fever virus, Zika virus, West Nile virus, Japanese encephalitis virus and tick-borne encephalitis virus. Nonstructural protein 1 (NS1) is a glycoprotein that encodes a 352-amino-acid polypeptide and has a molecular weight of 46-55 kDa depending on its glycosylation status. NS1 is highly conserved among multiple flaviviruses and occurs in distinct forms, including a dimeric form within the endoplasmic reticulum, a cell-associated form on the plasma membrane, or a secreted hexameric form (sNS1) trafficked to the extracellular matrix. Intracellular dimeric NS1 interacts with other NSs to participate in viral replication and virion maturation, while extracellular sNS1 plays a critical role in immune evasion, flavivirus pathogenesis and interactions with natural vectors. In this review, we provide an overview of recent research progress on flavivirus NS1, including research on the structural details, the secretory pathways in mammalian and mosquito cells and the multiple functions in viral replication, immune evasion, pathogenesis and interaction with natural hosts, drawing together the previous data to determine the properties of this protein.
Topics: Humans; Animals; Secretory Pathway; Mosquito Vectors; Flavivirus Infections; Zika Virus; Encephalitis Viruses, Tick-Borne; Zika Virus Infection; Mammals
PubMed: 37520540
DOI: 10.3389/fimmu.2023.1205002