scholarly journals DENV2 Pseudoviral Particles with Unprocessed Capsid Protein Are Assembled and Infectious

Viruses ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 27 ◽  
Author(s):  
Jyoti Rana ◽  
Oscar R. Burrone
Keyword(s):  
Dengue Virus ◽  
Capsid Protein ◽  
Proteolytic Processing ◽  
Viral Rna ◽  
Rna Packaging ◽  
Experimental Approaches ◽  
Anchor Sequence

Proteolytic processing of flavivirus polyprotein is a uniquely controlled process. To date, the sequential cleavage of the capsid anchor sequence at the junction of C-PrM has been considered essential for the production of flaviviruses. In this study, we used two experimental approaches to show the effect of unprocessed capsid on the production and infectivity of dengue virus 2 (DENV2) pseudoviral particles. The results showed that (1) both mature and unprocessed capsids of DENV2 were equally efficient in the viral RNA packaging and also in the assembly of infective particles; (2) DENV2 variants, in which the viral and host mediated cleavage of Ca peptide were independent, produced significantly higher levels of infective particles. Overall, this study demonstrated that unlike other flaviviruses, DENV2 capsid does not require a cleavable Ca sequence, and the sequential cleavage is not an obligatory requirement for the morphogenesis of infective pseudoviral particles.

scholarly journals Structural and Functional Properties of the Capsid Protein of Dengue and Related Flavivirus

2019 ◽  
Vol 20 (16) ◽  
pp. 3870 ◽  
Author(s):  
Faustino ◽  
Martins ◽  
Karguth ◽  
Artilheiro ◽  
Enguita ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Capsid Protein ◽  
Specific Binding ◽  
Protein A ◽  
Terminal Region ◽  
Viral Rna ◽  
Structural Protein ◽  
Virus Capsid ◽  
Structural And Functional Properties ◽  
Virus Capsid Protein

Dengue, West Nile and Zika, closely related viruses of the Flaviviridae family, are an increasing global threat, due to the expansion of their mosquito vectors. They present a very similar viral particle with an outer lipid bilayer containing two viral proteins and, within it, the nucleocapsid core. This core is composed by the viral RNA complexed with multiple copies of the capsid protein, a crucial structural protein that mediates not only viral assembly, but also encapsidation, by interacting with host lipid systems. The capsid is a homodimeric protein that contains a disordered N-terminal region, an intermediate flexible fold section and a very stable conserved fold region. Since a better understanding of its structure can give light into its biological activity, here, first, we compared and analyzed relevant mosquito-borne Flavivirus capsid protein sequences and their predicted structures. Then, we studied the alternative conformations enabled by the N-terminal region. Finally, using dengue virus capsid protein as main model, we correlated the protein size, thermal stability and function with its structure/dynamics features. The findings suggest that the capsid protein interaction with host lipid systems leads to minor allosteric changes that may modulate the specific binding of the protein to the viral RNA. Such mechanism can be targeted in future drug development strategies, namely by using improved versions of pep14-23, a dengue virus capsid protein peptide inhibitor, previously developed by us. Such knowledge can yield promising advances against Zika, dengue and closely related Flavivirus.

An experimental and theoretical approach to understand Fever, DENF & its cure

2020 ◽  
Vol 20 ◽  
Author(s):  
Vijay Kumar Vishvakarma ◽  
Ramesh Chandra ◽  
Prashant Singh
Keyword(s):  
Catalytic Activity ◽  
Dengue Virus ◽  
Theoretical Approach ◽  
Major Part ◽  
Genomic Structure ◽  
Denv Infection ◽  
Structural Proteins ◽  
Experimental Approaches ◽  
Ns3 Protease ◽  
Prime Target

: Fever is a response of human body due to an increase the temperature against the certain stimuli. It may be associated with several reasons and one of the major causes of fever is mosquito bite. Fever due to dengue virus (DENV) infection is being paid most attention out of several other fevers because of a large number of deaths reported worldwide. Dengue virus is transmitted by biting of the mosquitoes, Aedes aegypti and Aedes albopictus. DENV1, DENV2, DENV3 and DENV4 are the four serotypes of dengue virus and these serotypes have 65% similarities in their genomic structure. Genome of DENV is composed of single stranded RNA and it encodes for the polyprotein. Structural and non-structural proteins (nsP) are the two major part of protese. Researchers have paid high attention on the non-structural protease (nsP) of DENV like nsP1, nsP2A, nsP2B, nsP3, nsP4A, nsP4B and nsP5. The NS2B-NS3 protease of DENV is the prime target of the researchers as it is responsible for the catalytic activity. In the present time, Dengvaxia (vaccine) is being recommended to the patients suffering severely due to DENV infection in few countries only. Till date, neither a vaccine nor an effective medicine is available to combat with all four serotypes. This review describes the fever, its causes and studies to cure the infection due to DENV using theoretical and experimental approaches.

scholarly journals Reovirus Low-Density Particles Package Cellular RNA

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1096
Author(s):  
Timothy W. Thoner ◽  
Xiang Ye ◽  
John Karijolich ◽  
Kristen M. Ogden
Keyword(s):  
Rna Polymerase ◽  
Viral Proteins ◽  
Viral Rna ◽  
Low Density ◽  
Rna Packaging ◽  
Genome Packaging ◽  
Double Stranded Rna ◽  
Viral Genomes ◽  
Mammalian Orthoreovirus ◽  
Insight Into

Packaging of segmented, double-stranded RNA viral genomes requires coordination of viral proteins and RNA segments. For mammalian orthoreovirus (reovirus), evidence suggests either all ten or zero viral RNA segments are simultaneously packaged in a highly coordinated process hypothesized to exclude host RNA. Accordingly, reovirus generates genome-containing virions and “genomeless” top component particles. Whether reovirus virions or top component particles package host RNA is unknown. To gain insight into reovirus packaging potential and mechanisms, we employed next-generation RNA-sequencing to define the RNA content of enriched reovirus particles. Reovirus virions exclusively packaged viral double-stranded RNA. In contrast, reovirus top component particles contained similar proportions but reduced amounts of viral double-stranded RNA and were selectively enriched for numerous host RNA species, especially short, non-polyadenylated transcripts. Host RNA selection was not dependent on RNA abundance in the cell, and specifically enriched host RNAs varied for two reovirus strains and were not selected solely by the viral RNA polymerase. Collectively, these findings indicate that genome packaging into reovirus virions is exquisitely selective, while incorporation of host RNAs into top component particles is differentially selective and may contribute to or result from inefficient viral RNA packaging.

scholarly journals Dengue virus strain 2 capsid protein switches the annealing pathway and reduces intrinsic dynamics of the conserved 5’ untranslated region

RNA Biology ◽  
2021 ◽  
pp. 1-14
Author(s):  
Xin Ee Yong ◽  
Palur Venkata Raghuvamsi ◽  
Ganesh S. Anand ◽  
Thorsten Wohland ◽  
Kamal K. Sharma
Keyword(s):  
Dengue Virus ◽  
Capsid Protein ◽  
Virus Strain ◽  
Untranslated Region

scholarly journals Effects of Gag Mutation and Processing on Retroviral Dimeric RNA Maturation

2006 ◽  
Vol 80 (3) ◽  
pp. 1242-1249 ◽  
Author(s):  
William Fu ◽  
Que Dang ◽  
Kunio Nagashima ◽  
Eric O. Freed ◽  
Vinay K. Pathak ◽  
...  
Keyword(s):  
Viral Protein ◽  
Leukemia Virus ◽  
Viral Rna ◽  
Host Cells ◽  
Protein Cleavage ◽  
Rna Packaging ◽  
Virus Rna ◽  
Rna Dimer ◽  
Rna Maturation ◽  
Hiv 1

ABSTRACT After their release from host cells, most retroviral particles undergo a maturation process, which includes viral protein cleavage, core condensation, and increased stability of the viral RNA dimer. Inactivating the viral protease prevents protein cleavage; the resulting virions lack condensed cores and contain fragile RNA dimers. Therefore, protein cleavage is linked to virion morphological change and increased stability of the RNA dimer. However, it is unclear whether protein cleavage is sufficient for mediating virus RNA maturation. We have observed a novel phenotype in a murine leukemia virus capsid mutant, which has normal virion production, viral protein cleavage, and RNA packaging. However, this mutant also has immature virion morphology and contains a fragile RNA dimer, which is reminiscent of protease-deficient mutants. To our knowledge, this mutant provides the first evidence that Gag cleavage alone is not sufficient to promote RNA dimer maturation. To extend our study further, we examined a well-defined human immunodeficiency virus type 1 (HIV-1) Gag mutant that lacks a functional PTAP motif and produces immature virions without major defects in viral protein cleavage. We found that the viral RNA dimer in the PTAP mutant is more fragile and unstable compared with those from wild-type HIV-1. Based on the results of experiments using two different Gag mutants from two distinct retroviruses, we conclude that Gag cleavage is not sufficient for promoting RNA dimer maturation, and we propose that there is a link between the maturation of virion morphology and the viral RNA dimer.

scholarly journals Dengue Virus Capsid Protein Binding to Lipid Droplets and its Inhibition. towards a New Drug Target

2013 ◽  
Vol 104 (2) ◽  
pp. 415a
Author(s):  
Filomena A. Carvalho ◽  
Ivo C. Martins ◽  
Fabiana A. Carneiro ◽  
Iranaia Assunção-Miranda ◽  
André F. Faustino ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Protein Binding ◽  
Capsid Protein ◽  
Drug Target ◽  
Lipid Droplets ◽  
Virus Capsid ◽  
New Drug ◽  
Virus Capsid Protein

scholarly journals Encapsidation of Viral RNA inPicornavirales: Studies on Cowpea Mosaic Virus Demonstrate Dependence on Viral Replication

2018 ◽  
Vol 93 (2) ◽  
Author(s):  
Inga Kruse ◽  
Hadrien Peyret ◽  
Pooja Saxena ◽  
George P. Lomonossoff
Keyword(s):  
Viral Replication ◽  
Mosaic Virus ◽  
Viral Rna ◽  
Cowpea Mosaic Virus ◽  
Rna Packaging ◽  
Functional Link ◽  
Close Coupling ◽  
Genomic Rnas ◽  
Viral Rnas ◽  
Virus Like Particles

ABSTRACTTo elucidate the linkage between replication and encapsidation inPicornavirales, we have taken advantage of the bipartite nature of a plant-infecting member of this order, cowpea mosaic virus (CPMV), to decouple the two processes. RNA-free virus-like particles (empty virus-like particles [eVLPs]) can be generated by transiently coexpressing the RNA-2-encoded coat protein precursor (VP60) with the RNA-1-encoded 24,000-molecular-weight (24K) protease, in the absence of the replication machinery (K. Saunders, F. Sainsbury, and G. P. Lomonossoff, Virology 393:329–337, 2009, https://doi.org/10.1016/j.virol.2009.08.023). We have made use of the ability to produce assembled capsids of CPMV in the absence of replication to examine the putative linkage between RNA replication and packaging in thePicornavirales. We have created a series of mutant RNA-1 and RNA-2 molecules and have assessed the effects of the mutations on both the replication and packaging of the viral RNAs. We demonstrate that mutations that affect replication have a concomitant impact on encapsidation and that RNA-1-mediated replication is required for encapsidation of both RNA-1 and RNA-2. This close coupling between replication and encapsidation provides a means for the specific packaging of viral RNAs. Moreover, we demonstrate that this feature of CPMV can be used to specifically encapsidate custom RNA by placing a sequence of choice between the RNA-2 sequences required for replication.IMPORTANCEThe mechanism whereby members of the orderPicornaviralesspecifically package their genomic RNAs is poorly understood. Research with monopartite members of the order, such as poliovirus, indicated that packaging is linked to replication, although the presence of “packaging signals” along the length of the viral RNA has also been suggested. Thanks to the bipartite nature of the CPMV genome, which allows the manipulation of RNA-1 without modifying RNA-2, we show here that this specificity is due to a functional link between the two processes of viral replication and encapsidation. This has important implications for our understanding of the fundamental molecular biology ofPicornaviralesand opens the door to novel research and therapeutic applications in the field of custom RNA packaging and delivery technologies.

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