Post-translational regulation and modifications of flavivirus structural proteins
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The insights gained from research into post-translational regulation of structural proteins are beginning to be applied in the rational design of improved flavivirus vaccine candidates and make attractive targets for the development of novel therapeutics.Abstract:
Flaviviruses are a group of single-stranded, positive-sense RNA viruses that generally circulate between arthropod vectors and susceptible vertebrate hosts, producing significant human and veterinary disease burdens. Intensive research efforts have broadened our scientific understanding of the replication cycles of these viruses and have revealed several elegant and tightly co-ordinated post-translational modifications that regulate the activity of viral proteins. The three structural proteins in particular – capsid (C), pre-membrane (prM) and envelope (E) – are subjected to strict regulatory modifications as they progress from translation through virus particle assembly and egress. The timing of proteolytic cleavage events at the C–prM junction directly influences the degree of genomic RNA packaging into nascent virions. Proteolytic maturation of prM by host furin during Golgi transit facilitates rearrangement of the E proteins at the virion surface, exposing the fusion loop and thus increasing particle infectivity. Specific interactions between the prM and E proteins are also important for particle assembly, as prM acts as a chaperone, facilitating correct conformational folding of E. It is only once prM/E heterodimers form that these proteins can be secreted efficiently. The addition of branched glycans to the prM and E proteins during virion transit also plays a key role in modulating the rate of secretion, pH sensitivity and infectivity of flavivirus particles. The insights gained from research into post-translational regulation of structural proteins are beginning to be applied in the rational design of improved flavivirus vaccine candidates and make attractive targets for the development of novel therapeutics.read more
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Journal ArticleDOI
Biochemistry and Molecular Biology of Flaviviruses
Nicholas J. Barrows,Nicholas J. Barrows,Rafael K. Campos,Rafael K. Campos,Kuo-Chieh Liao,K. Reddisiva Prasanth,Ruben Soto-Acosta,Shih Chia Yeh,Geraldine Schott-Lerner,Julien Pompon,Julien Pompon,October M. Sessions,Shelton S. Bradrick,Mariano A. Garcia-Blanco,Mariano A. Garcia-Blanco +14 more
TL;DR: This review examines the molecular biology of flaviviruses touching on the structure and function of viral components and how these interact with host factors, and highlights the role of a noncoding RNA produced by flavIViruses to impair antiviral host immune responses.
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Zika Virus: the Latest Newcomer.
Juan-Carlos Saiz,Ángela Vázquez-Calvo,Ana B. Blázquez,Teresa Merino-Ramos,Estela Escribano-Romero,Miguel A. Martín-Acebes +5 more
TL;DR: Here, an extensively review what is currently known about ZIKV, from molecular biology, transmission routes, ecology, and epidemiology, to clinical manifestations, pathogenesis, diagnosis, prophylaxis, and public health.
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Structures and Functions of the Envelope Glycoprotein in Flavivirus Infections.
TL;DR: This review summarizes the structures and functions of ED I/II/III, and provides practical applications for the three domains, with the ultimate goal of implementing strategies to utilize the envelope protein against flavivirus infections, thus achieving better diagnostics and developing potential Flavivirus therapeutics and vaccines.
Journal ArticleDOI
Lipids and flaviviruses, present and future perspectives for the control of dengue, Zika, and West Nile viruses.
TL;DR: The current knowledge on the interactions of the flaviviruses with the cellular lipid metabolism is revised to identify potential targets for future antiviral development aimed to combat these relevant health-threatening pathogens.
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Zika Virus: Transmission, Detection, Control, and Prevention
Anshika Sharma,Sunil K. Lal +1 more
TL;DR: The existing evidences supporting the increasingly common prenatal microcephaly and GBS association and the current known ZIKV transmission dynamics, modes of detection (molecular and serology-based), and current control strategies are summarized in this review.
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TL;DR: The first structure of a flavivirus has been determined by using a combination of cryoelectron microscopy and fitting of the known structure of glycoprotein E into the electron density map, suggesting that flaviviruses employ a fusion mechanism in which the distal beta barrels of domain II of the glycop Protein E are inserted into the cellular membrane.
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TL;DR: The clustering of mutations that affect virulence in various flaviviruses indicates a possible receptor binding site and, together with other mutational and biochemical data, suggests a picture for the fusion-activating, conformational change triggered by low pH.
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