scholarly journals Three-Dimensional RNA Structure of the Major HIV-1 Packaging Signal Region

Structure ◽  
2013 ◽  
Vol 21 (6) ◽  
pp. 951-962 ◽  
Author(s):  
James D. Stephenson ◽  
Haitao Li ◽  
Julia C. Kenyon ◽  
Martyn Symmons ◽  
Dave Klenerman ◽  
...  
Keyword(s):  
Rna Structure ◽  
Three Dimensional ◽  
Packaging Signal ◽  
Signal Region ◽  
Hiv 1

scholarly journals HIV-1 Packaging Visualised by In-Gel SHAPE

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2389
Author(s):  
Aaron R. D’Souza ◽  
Dhivya Jayaraman ◽  
Ziqi Long ◽  
Jingwei Zeng ◽  
Liam J. Prestwood ◽  
...  
Keyword(s):  
Rna Structure ◽  
Structural Changes ◽  
Structural Protein ◽  
Packaging Signal ◽  
Packaging Process ◽  
Gag Polyprotein ◽  
Rna Conformation ◽  
Shape Selective ◽  
Insight Into ◽  
Hiv 1

HIV-1 packages two copies of its gRNA into virions via an interaction with the viral structural protein Gag. Both copies and their native RNA structure are essential for virion infectivity. The precise stepwise nature of the packaging process has not been resolved. This is largely due to a prior lack of structural techniques that follow RNA structural changes within an RNA–protein complex. Here, we apply the in-gel SHAPE (selective 2’OH acylation analysed by primer extension) technique to study the initiation of HIV-1 packaging, examining the interaction between the packaging signal RNA and the Gag polyprotein, and compare it with that of the NC domain of Gag alone. Our results imply interactions between Gag and monomeric packaging signal RNA in switching the RNA conformation into a dimerisation-competent structure, and show that the Gag–dimer complex then continues to stabilise. These data provide a novel insight into how HIV-1 regulates the translation and packaging of its genome.

scholarly journals Potential Achilles heels of SARS-CoV-2 displayed by the base order-dependent component of RNA folding energy

2020 ◽  
Author(s):  
Chiyu Zhang ◽  
Donald R. Forsdyke
Keyword(s):  
Rna Structure ◽  
Folding Energy ◽  
Packaging Signal ◽  
Antiviral Compound ◽  
N Protein ◽  
Gag Polyprotein ◽  
Protein Encoding ◽  
Dependent Component ◽  
High Base ◽  
Hiv 1

ABSTRACTBase order, not composition, best reflects local evolutionary pressure for folding of single-stranded nucleic acids. The base order-dependent component of folding energy has revealed a highly conserved region in HIV-1 genomes that associates with RNA structure. This corresponds to a packaging signal that is recognized by the nucleocapsid domain of the Gag polyprotein. Long viewed as a potential HIV-1 “Achilles heel,” the signal can be targeted by a recently described antiviral compound (NSC 260594) or by synthetic oligonucleotides. Thus, a conserved base-order-rich region of HIV-1 may facilitate therapeutic attack. Although SARS-CoV-2 differs in many respects from HIV-1, the same technology displays regions with a high base order-dependent folding energy component, which are also highly conserved. This indicates structural invariance (SI) sustained by natural selection. While the regions are often also protein-encoding (e.g. NSP3, ORF3a), we suggest that their nucleic acid level functions – such as the ribosomal frameshifting element (FSE) that facilitates differential expression of 1a and 1ab polyproteins – can be considered potential “Achilles heels” for SARS-CoV-2, perhaps susceptible to therapies like those envisaged for AIDS. The region of the FSE scored well, but higher SI scores were obtained in other regions, including those encoding NSP13 and the nucleocapsid (N) protein.

3D-QSAR Studies of S-DABO Derivatives as Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors

2019 ◽  
Vol 16 (8) ◽  
pp. 868-881
Author(s):  
Yueping Wang ◽  
Jie Chang ◽  
Jiangyuan Wang ◽  
Peng Zhong ◽  
Yufang Zhang ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Three Dimensional ◽  
Predictive Ability ◽  
3D Qsar ◽  
Binding Mode ◽  
Quantitative Structure Activity Relationship ◽  
Field Analysis ◽  
Reverse Transcriptase Inhibitors ◽  
Qsar Studies ◽  
Hiv 1

Background: S-dihydro-alkyloxy-benzyl-oxopyrimidines (S-DABOs) as non-nucleoside reverse transcriptase inhibitors have received considerable attention during the last decade due to their high potency against HIV-1. Methods: In this study, three-dimensional quantitative structure-activity relationship (3D-QSAR) of a series of 38 S-DABO analogues developed in our lab was studied using Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA). The Docking/MMFF94s computational protocol based on the co-crystallized complex (PDB ID: 1RT2) was used to determine the most probable binding mode and to obtain reliable conformations for molecular alignment. Statistically significant CoMFA (q2=0.766 and r2=0.949) and CoMSIA (q2=0.827 and r2=0.974) models were generated using the training set of 30 compounds on the basis of hybrid docking-based and ligand-based alignment. Results: The predictive ability of CoMFA and CoMSIA models was further validated using a test set of eight compounds with predictive r2 pred values of 0.843 and 0.723, respectively. Conclusion: The information obtained from the 3D contour maps can be used in designing new SDABO derivatives with improved HIV-1 inhibitory activity.

Using three-dimensional substructure searching to identify novel, non-peptidic inhibitors of HIV-1 protease

1990 ◽  
Vol 3 (6) ◽  
pp. 673-680 ◽  
Author(s):  
Mark G. Bures ◽  
Charles W. Hutchins ◽  
Mary Maus ◽  
William Kohlbrenner ◽  
Sunil Kadam ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Peptidic Inhibitors ◽  
Hiv 1

Cost-Effective High-Speed, Three-Dimensional Live-Cell Imaging of HIV-1 Transfer at the T Cell Virological Synapse

2021 ◽  
Author(s):  
Alice Sandmeyer ◽  
Lili Wang ◽  
Wolfgang Hübner ◽  
Marcel Müller ◽  
Benjamin Chen ◽  
...  
Keyword(s):  
T Cell ◽  
Live Cell Imaging ◽  
High Speed ◽  
Cell Imaging ◽  
Three Dimensional ◽  
Cost Effective ◽  
Live Cell ◽  
Virological Synapse ◽  
Hiv 1

scholarly journals The Mechanism of HIV-1 Core Assembly: Insights from Three-Dimensional Reconstructions of Authentic Virions

Structure ◽  
2006 ◽  
Vol 14 (1) ◽  
pp. 15-20 ◽  
Author(s):  
John A.G. Briggs ◽  
Kay Grünewald ◽  
Bärbel Glass ◽  
Friedrich Förster ◽  
Hans-Georg Kräusslich ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Hiv 1

Structure and Stability of Wild-type and Mutant RNA Internal Loops from the SL-1 Domain of the HIV-1 Packaging Signal

2002 ◽  
Vol 322 (3) ◽  
pp. 543-557 ◽  
Author(s):  
Jane Greatorex ◽  
José Gallego ◽  
Gabriele Varani ◽  
Andrew Lever
Keyword(s):  
Wild Type ◽  
Packaging Signal ◽  
Structure And Stability ◽  
Internal Loops ◽  
Hiv 1

scholarly journals A new subclass of exoribonuclease resistant RNA found in multiple Flaviviridae genera

2020 ◽  
Author(s):  
Matthew J. Szucs ◽  
Parker J. Nichols ◽  
Rachel A. Jones ◽  
Quentin Vicens ◽  
Jeffrey S. Kieft
Keyword(s):  
Rna Structure ◽  
Three Dimensional ◽  
Viral Rna ◽  
Human Pathogens ◽  
Virus Family ◽  
Innovative Strategies ◽  
Virus Rna ◽  
High Resolution Structure ◽  
Cellular Machinery ◽  
Rna Maturation

ABSTRACTViruses have developed innovative strategies to exploit the cellular machinery and overcome the host antiviral defenses, often using specifically structured RNA elements. Examples are found in flaviviruses; during flaviviral infection, pathogenic subgenomic flaviviral RNAs (sfRNAs) accumulate in the cell. These sfRNAs are formed when a host cell 5’ to 3’ exoribonuclease degrades the viral genomic RNA but is blocked by an exoribonuclease resistant RNA structure (xrRNA) located in the viral genome’s 3’untranslated region (UTR). Although known to exist in several Flaviviridae genera the full distribution and diversity of xRNAs in this virus family was unknown. Using the recent high-resolution structure of an xrRNA from the divergent flavivirus Tamana bat virus (TABV) as a reference, we used bioinformatic searches to identify xrRNA in the Pegivirus, Pestivirus, and Hepacivirus genera. We biochemically and structurally characterized several examples, determining that they are genuine xrRNAs with a conserved fold. These new xrRNAs look superficially similar to the previously described xrRNAs but possess structural differences making them distinct from previous classes of xrRNAs. Our findings thus require adjustments of previous xrRNA classification schemes and expand on the previously known distribution of the xrRNA in Flaviviridae, indicating their widespread distribution and illustrating their importance.IMPORTANCEThe Flaviviridae comprise one of the largest families of positive sense single stranded (+ssRNA) and it is divided into the Flavivirus, Pestivirus, Pegivirus, and Hepacivirus genera. The genus Flavivirus contains many medically relevant viruses such as Zika Virus, Dengue Virus, and Powassan Virus. In these, a part of the virus’s RNA twists up into a very special three-dimensional shape called an xrRNA that blocks the ability of the cell to “chew up” the viral RNA. Hence, part of the virus’ RNA remains intact, and this protected part is important for viral infection. This was known to occur in Flaviviruses but whether it existed in the other members of the family was not known. In this study, we not only identified a new subclass of xrRNA found in Flavivirus but also in the remaining three genera. The fact that this process of viral RNA maturation exists throughout the entire Flaviviridae family makes it clear that this is an important but underappreciated part of the infection strategy of these diverse human pathogens.

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