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TMEM41B Is a Pan-flavivirus Host Factor.

Flaviviruses pose a constant threat to human health. These RNA viruses are transmitted by the bite of infected mosquitoes and ticks and regularly cause outbreaks. To identify host factors required for flavivirus infection, we performed full-genome loss of function CRISPR-Cas9 screens. Based on these results, we focused our efforts on characterizing the roles that TMEM41B and VMP1 play in the virus replication cycle. Our mechanistic studies on TMEM41B revealed that all members of the Flaviviridae family that we tested require TMEM41B. We tested 12 additional virus families and found that SARS-C…

Organization of the Flavivirus RNA replicase complex.

Flaviviruses, such as dengue, Japanese encephalitis, West Nile, yellow fever, and Zika viruses, are serious human pathogens that cause significant morbidity and mortality globally each year. Flaviviruses are single-stranded, positive-sense RNA viruses, and encode two multidomain proteins, NS3 and NS5, that possess all enzymatic activities required for genome replication and capping. NS3 and NS5 interact within virus-induced replication compartments to form the RNA genome replicase complex. Although the individual enzymatic activities of both proteins have been extensively studied and are well …

Stability of a Tick-Borne Flavivirus in Milk.

The tick-borne flaviviruses (TBFV) occur worldwide and the tick-borne encephalitis virus (TBEV) members of the group often cause severe, debilitating neurological disease in humans. Although the primary route of infection is through the bite of an infected tick, alimentary infection through the consumption of TBEV-contaminated dairy products is also well-documented and is responsible for some disease in endemic areas. Experimental infection of goats, cattle, and sheep with TBEV shows that the virus can be excreted in the milk of infected animals. Additionally, the virus remains infectious afte…

[New approaches to the treatment of the flavivirus infections].

Since spontaneous mutagenesis and quasi-species rearrangements of the RNA-containing viruses, as well as an absence of both viral and cellular RNA reparation systems, causes resistance to originally effective antiviral drugs, combination therapy with nucleoside and non-nucleoside inhibitors of the viral enzymes in combination with immunomodulators is recommended. The use of specific immunoglobulins does not result in complete elimination of the flaviviruses but rather in possible antibody-dependent enhancement of the flavivirus infection by means of increased penetration of complexes of virion…

Usutu virus: an emerging flavivirus in Europe.

Usutu virus (USUV) is an African mosquito-borne flavivirus belonging to the Japanese encephalitis virus serocomplex. USUV is closely related to Murray Valley encephalitis virus, Japanese encephalitis virus, and West Nile virus. USUV was discovered in South Africa in 1959. In Europe, the first true demonstration of circulation of USUV was reported in Austria in 2001 with a significant die-off of Eurasian blackbirds. In the subsequent years, USUV expanded to neighboring countries, including Italy, Germany, Spain, Hungary, Switzerland, Poland, England, Czech Republic, Greece, and Belgium, where i…

Flavivirus NS5 Prevents the InSTATement of IFN.

Given the potency of interferon-α/β, viral evasion of this pathway is crucial for infection. In this issue of Cell Host & Microbe, Laurent-Rolle et al. (2014) report that during yellow fever virus infection, interferon-α/β stimulates the polyubiquitination of viral NS5, which binds to STAT2 and inhibits transcription of interferon-stimulated genes.

Constancy and diversity in the flavivirus fusion peptide.

BACKGROUND: Flaviviruses include the mosquito-borne dengue, Japanese encephalitis, yellow fever and West Nile and the tick-borne encephalitis viruses. They are responsible for considerable world-wide morbidity and mortality. Viral entry is mediated by a conserved fusion peptide containing 16 amino acids located in domain II of the envelope protein E. Highly orchestrated conformational changes initiated by exposure to acidic pH accompany the fusion process and are important factors limiting amino acid changes in the fusion peptide that still permit fusion with host cell membranes in both arthro…

Structure and function of flavivirus NS5 methyltransferase.

The plus-strand RNA genome of flavivirus contains a 5' terminal cap 1 structure (m7GpppAmG). The flaviviruses encode one methyltransferase, located at the N-terminal portion of the NS5 protein, to catalyze both guanine N-7 and ribose 2'-OH methylations during viral cap formation. Representative flavivirus methyltransferases from dengue, yellow fever, and West Nile virus (WNV) sequentially generate GpppA-->m7GpppA-->m7GpppAm. The 2'-O methylation can be uncoupled from the N-7 methylation, since m7GpppA-RNA can be readily methylated to m7GpppAm-RNA. Despite exhibiting two distinct methylation ac…

Traditional and novel approaches to flavivirus vaccines.

Yellow fever, dengue, Japanese encephalitis and tick-borne encephalitis viruses are the medically most important members of the Flavivirus genus composed primarily of arboviruses. In this paper, we review the commercially available traditional flavivirus vaccines against yellow fever, Japanese encephalitis, and tick-borne encephalitis, as well as modern approaches to flavivirus vaccines. Formalin inactivation technology has been employed to produce killed vaccines. Flaviviruses have been attenuated by multiple passages in animal tissues and cell cultures to produce empirical live attenuated va…

Flavivirus Capsid Proteins Inhibit the Interferon Response.

Zika virus (ZIKV) establishes persistent infections in multiple human tissues, a phenomenon that likely plays a role in its ability to cause congenital birth defects and neurological disease. Multiple nonstructural proteins encoded by ZIKV, in particular NS5, are known to suppress the interferon (IFN) response by attacking different steps in this critical antiviral pathway. Less well known are the potential roles of structural proteins in affecting the host immune response during ZIKV infection. Capsid proteins of flaviviruses are of particular interest because a pool of these viral proteins i…

Anti-flavivirus Properties of Lipid-Lowering Drugs.

Although Flaviviruses such as dengue (DENV) and zika (ZIKV) virus are important human pathogens, an effective vaccine or antiviral treatment against them is not available. Hence, the search for new strategies to control flavivirus infections is essential. Several studies have shown that the host lipid metabolism could be an antiviral target because cholesterol and other lipids are required during the replicative cycle of different Flaviviridae family members. FDA-approved drugs with hypolipidemic effects could be an alternative for treating flavivirus infections. However, a better understandin…

How NS1 Antibodies Prevent Severe Flavivirus Disease.

The flavivirus genus consists of several major human pathogens including dengue (DENV) and Zika viruses. The flavivirus nonstructural protein 1 (NS1) plays an important role in disease progression, for example, in the development of severe dengue disease. Anti-NS1 antibodies have been shown to confer protection, and two new studies by Biering et al. and Modhiran et al. on the structure of NS1:antibody complexes reveal their mechanism of neutralization.

Mechanism through Which Retrocyclin Targets Flavivirus Multiplication.

Currently, there are no approved drugs for the treatment of flavivirus infection. Accordingly, we tested the inhibitory effects of the novel θ-defensin retrocyclin-101 (RC-101) against flavivirus infection and investigated the mechanism underlying the potential inhibitory effects. First, RC-101 robustly inhibited both Japanese encephalitis virus (JEV) and Zika virus (ZIKV) infections. RC-101 exerted inhibitory effects on the entry and replication stages. Results also indicated that the nonstructural protein NS2B-NS3 serine protease might serve as a potential viral target. Furthermore, RC-101 i…

Toward universal flavivirus identification by mass cataloging.

Development of rapid and specific molecular diagnostics for flaviviruses remains an important global health challenge. Herein a platform technology using mass spectrometry that can be used for universal identification and genotyping of these viruses is described. The feasibility of the approach is demonstrated by using it to correctly identify and serotype two strains of dengue virus. Predictive calculations show that the approach can be expected to be equally efficacious for the identification and epidemiological tracking of other flaviviruses including West Nile, Japanese encephalitis, and Y…

Human T Cell Responses to Flavivirus Vaccines.

Flaviviruses are major human pathogens that continue to pose a global health threat, and vaccination is an effective strategy to protect against disease from several flaviviruses. Flavivirus vaccines are believed to confer protection primarily through antibody responses; however, the role of T cells in vaccine immunity remains less explored despite demonstrated contribution in the response to natural infection. This review examines T cell responses induced by licensed or developing flavivirus vaccines, their contribution to protection, and key findings highlighting the importance of cellular i…

Разработка и отбор вакцины от флавивируса.

Вакцина ДНК — это плазмид, кодирующий антиген вакцины вместе с эффективным эукариотическим промоутером для обеспечения белкового выражения. Главной проблемой вакцин ДНК является их субоптимальная иммуногенность у людей. Многие различные флавивирусы заражаются и вызывают серьезные заболевания и даже смерть у людей, но вакцины от большинства соответствующих флавивирусов отсутствуют, за исключением японского энцефалита. Вакцины ДНК легко и быстро производятся при относительно низких затратах, не требуют обработки опасных патогенов, стабильны при комнатной температуре, что позволяет производить и

Совпадение в аннотации оригинала
A DNA vaccine is a plasmid encoding a vaccine antigen together with an efficient eukaryotic promoter to drive protein expression. The chief problem of DNA vaccines has been their suboptimal immunogenicity in humans. Many different flaviviruses infect and cause serious illness and even death in humans, but human vaccines are not available against most of the …

Flavivirus Receptors: Diversity, Identity, and Cell Entry.

Flaviviruses are emerging and re-emerging arthropod-borne pathogens responsible for significant mortality and morbidity worldwide. The genus comprises more than seventy small, positive-sense, single-stranded RNA viruses, which are responsible for a spectrum of human and animal diseases ranging in symptoms from mild, influenza-like infection to fatal encephalitis and haemorrhagic fever. Despite genomic and structural similarities across the genus, infections by different flaviviruses result in disparate clinical presentations. This review focusses on two haemorrhagic flaviviruses, dengue virus …

Flavivirus NS1: a multifaceted enigmatic viral protein.

Flaviviruses are emerging arthropod-borne viruses representing an immense global health problem. The prominent viruses of this group include dengue virus, yellow fever virus, Japanese encephalitis virus, West Nile virus tick borne encephalitis virus and Zika Virus. These are endemic in many parts of the world. They are responsible for the illness ranging from mild flu like symptoms to severe hemorrhagic, neurologic and cognitive manifestations leading to death. NS1 is a highly conserved non-structural protein among flaviviruses, which exist in diverse forms. The intracellular dimer form of NS1…

Research advances in plant-made flavivirus antigens.

Outbreaks of flaviviruses such as dengue (DV), yellow fever (YFV), Japanese encephalitis (JEV), tick-borne encephalitis (TBEV) and West Nile (WNV) affect numerous countries around the world. The fast spread of these viruses is the result of increases in the human population, rapid urbanisation and globalisation. While vector control is an important preventive measure against vector-borne diseases, it has failed to prevent the spread of these diseases, particularly in developing countries where the implementation of control measures is intermittent. As antiviral drugs against flaviviruses are n…

[Prospects for treating mosquito-borne flavivirus encephalitides].

The Japanese encephalitis virus and West Nile virus belong to the family Flaviviridae, genus Flavivirus; they have a similar transmission cycle, with birds serving as the natural vertebrate host and mosquitoes, primarily, Culex species, both serving as the enzootic vectors and infecting humans. These arboviruses have caused more human cases of severe neuroinvasive disease worldwide during the past decade than other mosquito-borne flaviviruses. The current data and concepts on the clinical manifestations, pathogenesis, diagnosis, and treatment of infections caused by West Nile virus and Japanes…