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Trends in flavivirus infections in Japan.

Although Japanese encephalitis has declined as an important cause of illness and death in Japan, infection with other flaviviruses has become a public health concern. Recently, reports of imported dengue cases, as well as isolations of tick-borne encephalitis virus, have increased.

Pathogenesis and virulence of flavivirus infections.

The Flavivirus genus consists of >70 members including several that are considered significant human pathogens. Flaviviruses display a broad spectrum of diseases that can be roughly categorised into two phenotypes - systemic disease involving haemorrhage exemplified by dengue and yellow Fever virus, and neurological complications associated with the likes of West Nile and Zika viruses. Attempts to develop vaccines have been variably successful against some. Besides, mosquito-borne flaviviruses can be vertically transmitted in the arthropods, enabling long term persistence and the possibility o…

The Complement System in Flavivirus Infections.

The incidence of flavivirus infections has increased dramatically in recent decades in tropical and sub-tropical climates worldwide, affecting hundreds of millions of people each year. The Flaviviridae family includes dengue, West Nile, Zika, Japanese encephalitis, and yellow fever viruses that are typically transmitted by mosquitoes or ticks, and cause a wide range of symptoms, such as fever, shock, meningitis, paralysis, birth defects, and death. The flavivirus genome is composed of a single positive-sense RNA molecule encoding a single viral polyprotein. This polyprotein is further processe…

Attenuation of the Langat tick-borne flavivirus by chimerization with mosquito-borne flavivirus dengue type 4.

Langat virus (LGT) strain TP21 is the most attenuated of the tick-borne flaviviruses for humans. Even though LGT has low-level neurovirulence for humans, it, and its more attenuated egg-passage derivative, strain E5, exhibit significant neurovirulence and neuroinvasiveness in normal mice, albeit less than that associated with tick-borne encephalitis virus (TBEV), the most virulent of the tick-borne flaviviruses. We sought to reduce or ablate these viral phenotypes of TP21 and E5 by using a strategy that had been used successfully in the past to reduce neurovirulence and abolish neuroinvasivene…

Flavivirus-based bivalent nanoparticle vaccines induce neutralizing antibodies and Th1 responses against flavivirus and coupling antigens.

Effective vaccines against flaviviruses, including Japanese encephalitis virus (JEV), are widely used. We developed antigen-loaded nanoparticle vaccines, using JEV virus-like particles (JEV-VLPs) as carriers. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (S-RBD) was covalently coupled to specific peptide insertion sites on the JEV envelope protein. Mice immunized with these coupled particles (JEprME-S-RBD) produced high levels of neutralizing antibodies against both JEV and SARS-CoV-2, with broad activity against multiple SARS-CoV-2 variants. Th…

Flavivirus: From Structure to Therapeutics Development.

Flaviviruses are still a hidden threat to global human safety, as we are reminded by recent reports of dengue virus infections in Singapore and African-lineage-like Zika virus infections in Brazil. Therapeutic drugs or vaccines for flavivirus infections are in urgent need but are not well developed. The Flaviviridae family comprises a large group of enveloped viruses with a single-strand RNA genome of positive polarity. The genome of flavivirus encodes ten proteins, and each of them plays a different and important role in viral infection. In this review, we briefly summarized the major informa…

Molecular Determinants of Flavivirus Virion Assembly.

Virion assembly is an important step in the life cycle of all viruses. For viruses of the Flavivirus genus, a group of enveloped positive-sense RNA viruses, the assembly step represents one of the least understood processes in the viral life cycle. While assembly is primarily driven by the viral structural proteins, recent studies suggest that several nonstructural proteins also play key roles in coordinating the assembly and packaging of the viral genome. This review focuses on describing recent advances in our understanding of flavivirus virion assembly, including the intermolecular interact…

Recent advances in human flavivirus vaccines.

Dengue (DENV), West Nile (WNV) and Zika (ZIKV) viruses are mosquito-transmitted flaviviruses that cause thousands of human deaths and millions of illnesses each year. In the last decades, epidemic outbreaks of all three flaviviruses emerged and caused a major health and economical problem in many parts of the world. The increasing and expanding burden of flaviviruses has highlighted the need for effective human vaccines against all three viruses. This review provides an overview of the recent progress in DENV, WNV and ZIKV vaccines development with specific focus on candidates in human clinica…

Regulation of Apoptosis during Flavivirus Infection.

Apoptosis is a type of programmed cell death that regulates cellular homeostasis by removing damaged or unnecessary cells. Its importance in host defenses is highlighted by the observation that many viruses evade, obstruct, or subvert apoptosis, thereby blunting the host immune response. Infection with Flaviviruses such as Japanese encephalitis virus (JEV), Dengue virus (DENV) and West Nile virus (WNV) has been shown to activate several signaling pathways such as endoplasmic reticulum (ER)-stress and AKT/PI3K pathway, resulting in activation or suppression of apoptosis in virus-infected cells.…

Flavivirus cell entry and membrane fusion.

Flaviviruses, such as dengue virus and West Nile virus, are enveloped viruses that infect cells through receptor-mediated endocytosis and fusion from within acidic endosomes. The cell entry process of flaviviruses is mediated by the viral E glycoprotein. This short review will address recent advances in the understanding of flavivirus cell entry with specific emphasis on the recent study of Zaitseva and coworkers, indicating that anionic lipids might play a crucial role in the fusion process of dengue virus [1].

Recent advancement in flavivirus vaccine development.

Lately, the magnitude of cumulative diseases burden caused by flaviviruses, such as dengue virus, Japanese encephalitis virus, tick-borne encephalitis virus, West Nile virus and yellow fever virus, has reached an unprecedented level with the sizes of human and animal populations at risk increasing sharply. These diseases present highly complex medical, economic and ecologic problems, some effecting primarily human and others affecting human, livestock and wildlife. The large body of recent publications on the development of vaccines taking advantage of new generations of bio-engineering techni…

[Heterogeneity of virus-specific flavivirus proteins].

The polyacrylamide gel analysis of large intracellular virus-specific proteins NV5, NV4, and the intracellular form of structural protein V3 established differences in the electrophoretic mobility of each of these proteins formed in cells infected with tick-borne encephalitis, Powassan, Langat, and West Nile viruses. It is assumed that these differences in the electrophoretic mobility of NV5, NV4 proteins, and the intracellular form of V3 protein reflect the differences in the primary structure of each of these proteins in the viruses examined.

Leukocyte recruitment in flavivirus-induced encephalitis.

Flaviviruses are capable of causing a myriad of diseases in humans, including viral encephalitis. This condition involves complex interactions between the virus, resident cells of the central nervous system and leukocytes recruited to the brain. We reviewed the mechanisms underlying leukocyte recruitment during flavivirus-induced encephalitis with a focus on the role of various chemoattractants and adhesion molecules. We discuss how these molecules orchestrate the migration of peripheral leukocytes into the brain parenchyma and how neurotropic flaviviruses induce this process. Moreover, we dis…

Флавивирусное заражение связано с цереброваскулярными событиями.

Вирусы (арбовирусы) рода Флавивируса распространяются во всем мире и ежегодно приводят к значительным человеческим заболеваниям и смертности. Инфекции флавивируса представляют собой спектр клинических проявлений, начиная от асимптоматических и заканчивая серьезными проявлениями, включая кровоизлияние, энцефалит и смерть. В этой связи мы описываем 3 сообщения о цереброваскулярной причастности к пациентам, зараженным вирусами денге и зика, в Сан-Хосе-ду-Рио-Прето, штате Сан-Паулу, Бразилия, где наблюдается гипер-эпидемиологическая циркуляция арбовирусов, включая денге, желтую лихорадку, чикунгун

Совпадение в аннотации оригинала
Arthropod-borne viruses (arboviruses) of the genus Flavivirus are distributed globally and cause significant human disease and mortality annually. Flavivirus infections present a spectrum of clinical manifestations, ranging from asymptomatic to severe manifestations, including hemorrhage, encephalitis and death. Herein, we describe 3 case reports of cerebrov…

Memory T Cells in Flavivirus Vaccination.

Flaviviruses include many medically important viruses, such as Dengue virus (DENV), Japanese encephalitis (JEV), tick-borne encephalitis (TBEV), West Nile (WNV), yellow fever (YFV), and Zika viruses (ZIKV). Currently, there are licensed human vaccines for DENV, JEV, TBEV and YFV, but not for WNV or ZIKV. Memory T cells play a central role in adaptive immunity and are important for host protection during flavivirus infection. In this review, we discuss recent findings from animal models and clinical trials and provide new insights into the role of memory T cells in host protective immunity upon…

Antiviral macrophage responses in flavivirus encephalitis.

Mosquito-borne flaviviruses are a major current and emerging threat, affecting millions of people worldwide. Global climate change, combined with increasing proximity of humans to animals and mosquito vectors by expansion into natural habitats, coupled with the increase in international travel, have resulted in significant spread and concomitant increase in the incidence of infection and severe disease. Although neuroinvasive disease has been well described for some viral infections such as Japanese Encephalitis virus (JEV) and West Nile virus (WNV), others such as dengue virus (DENV) have rec…

Novel approaches to flavivirus drug discovery.

INTRODUCTION: The members of the family Flaviviridae, including West Nile virus, yellow fever virus and dengue virus, are important human pathogens that are expanding their impact around the globe. The four serotypes of dengue infect 50-100 million people each year, yet the only clinical treatment is supportive care to reduce symptoms. Drugs that employ novel inhibition mechanisms and targets are urgently needed to combat the growing incidence of dengue worldwide. AREAS COVERED: The authors discuss recently discovered flavivirus inhibitors with a focus on antivirals targeting non-enzymatic pr…

Bioinformatics in new generation flavivirus vaccines.

Flavivirus infections are the most prevalent arthropod-borne infections world wide, often causing severe disease especially among children, the elderly, and the immunocompromised. In the absence of effective antiviral treatment, prevention through vaccination would greatly reduce morbidity and mortality associated with flavivirus infections. Despite the success of the empirically developed vaccines against yellow fever virus, Japanese encephalitis virus and tick-borne encephalitis virus, there is an increasing need for a more rational design and development of safe and effective vaccines. Seve…