https://orcid.org/0000-0002-7950-9226
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ABSTRACT
Viruses remain a global threat to animals, plants, and humans. The type 1 human immunodeficiency virus (HIV-1) is a member of the retrovirus family and carries an RNA genome, which is reverse transcribed into viral DNA and further integrated into the host-cell DNA for viral replication and proliferation. The RNA structures from the HIV-1 genome provide valuable insights into the mechanisms underlying the viral replication cycle. Moreover, these structures serve as models for designing novel therapeutic approaches. Here, we review structural data on RNA from the HIV-1 genome as well as computational studies based on these structural data. The review is organized according to the type of structured RNA element which contributes to different steps in the viral replication cycle. This is followed by an overview of the HIV-1 transactivation response element (TAR) RNA as a model system for understanding dynamics and interactions in the viral RNA systems. The review concludes with a description of computational studies, highlighting the impact of biomolecular simulations in elucidating the mechanistic details of various steps in the HIV-1’s replication cycle.
Acronyms
| ACB | = | Anticodon-binding domain |
| AFM | = | Atomic force microscopy |
| AIDS | = | Acquired immunodeficiency syndrome |
| AMBER | = | Assisted Model Building with Energy Refinement |
| ARL | = | A-rich loop |
| ARM | = | Arginine rich motif |
| ART | = | Antiretroviral therapy |
| BMH | = | Branched multiple hairpin state |
| CA | = | Capsid |
| CDK9 | = | Cyclin-dependent kinase 9 |
| CG | = | Coarse-grained |
| CHARMM | = | Chemistry at Harvard Macromolecular Mechanics |
| CLIP-seq | = | Crosslinking-immunoprecipitation sequencing |
| CRISPR | = | Clustered regularly interspaced short palindromic repeats |
| cryo-EM | = | Cryo-electron microscopy |
| DFT | = | Density functional theory |
| DIS | = | Dimerization initiation site |
| DNA | = | Deoxyribonucleic acid |
| dsRNA | = | Double-stranded ribonucleic acid |
| DENV | = | Dengue Virus |
| Env | = | Envelope-glycoprotein |
| ES | = | Excited state |
| ESS | = | Exonic splicing silencer |
| gRNA | = | Genomic ribonucleic acid |
| FEP | = | Free energy perturbation |
| FSS | = | Frameshift stimulating structure |
| Gag | = | Group-specific antigen |
| HIV-1 | = | Type 1 Human Immunodeficiency Virus |
| HJH | = | Helix-junction-helix |
| hLysRS | = | Human lysyl-tRNA synthetase |
| HCV | = | Hepatitis C Virus |
| IN | = | Integrase |
| IRES | = | Internal ribosome entry site |
| ITC | = | Isothermal titration calorimetry |
| lncRNA | = | Long non-coding ribonucleic acid |
| LDI | = | Long-distance interaction state |
| LTR | = | Long terminal repeat |
| MA | = | Matrix |
| MD | = | Molecular dynamics |
| miRNA | = | Micro ribonucleic acid |
| MM-GBSA | = | Molecular mechanics with generalized Born and surface area solvation |
| mRNA | = | Messenger ribonucleic acid |
| NC | = | Nucleocapsid |
| NCp7 | = | Nucleocapsid protein 7 |
| NF45 | = | Nuclear factor 45 |
| NF90 | = | Nuclear factor 90 |
| NMR | = | Nuclear magnetic resonance |
| NNRTI | = | Non-nucleoside reverse transcriptase inhibitor |
| ORF | = | Open reading frame |
| P-TEFb | = | Positive transcript elongation factor b |
| PAF-1 | = | Polymerase-associated factor 1 |
| PAS | = | Primer activation site |
| PBE | = | Poisson-Boltzmann equation |
| PBS | = | Primer binding site |
| PCA | = | Principle component analysis |
| PDB | = | Protein Data Bank |
| PRF | = | Programmed ribosomal frameshift |
| Psi | = | Packaging signal |
| RAM | = | Replica-averaged metadynamics |
| RDC | = | Residual dipolar coupling |
| Rev | = | Regulator of expression of virion |
| RNA | = | Ribonucleic acid |
| RNase H | = | Ribonuclease H |
| RT | = | Reverse transcriptase |
| RTIC | = | Reverse transcription initiation complex |
| RRE | = | Rev response element |
| RSV | = | Rous sarcoma virus |
| SEC | = | Super elongation complex |
| SHAPE | = |
|
| SL1 | = | Stem-loop 1 |
| SMD | = | Steered molecular dynamics |
| SMFS | = | Single-molecule force spectroscopy |
| ssRNA-RT | = | Positive sense single-stranded ribonucleic acid with deoxyribonucleic acid intermediates |
| ssDNA | = | Single-stranded deoxyribonucleic acid |
| SARS | = | Severe acute respiratory syndrome |
| Tat | = | Transactivator of transcription |
| TBP | = | TAR-binding proteins |
| TLE | = | tRNA-like element |
| tRNA | = | Transfer ribonucleic acid |
| TAR | = | Transactivation response element |
| ZIKV | = | Zika Virus |
| URL | = | U-rich Loop |
| UTR | = | Untranslated region |
| vDNA | = | Viral deoxyribonucleic acid |
| XSI | = | X-ray scattering interferometry |
Acknowledgments
We acknowledge the financial support from the National Institutes of Health (R35GM138217) and from the National Science Foundation (CBET-1554558).
Disclosure statement
No potential conflict of interest was reported by the authors.