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Related Concept Videos

Retrovirus Life Cycles01:10

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Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
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The early endosome containing internalized molecules matures through transformations in its location, morphology, intraluminal pH, and membrane protein composition. Together, these changes result in a more acidic late endosome that contains multiple intraluminal vesicles; therefore, the late endosome is also called a multivesicular body (MVB).
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A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
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Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
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LTR retrotransposons are class I transposable elements with long terminal repeats flanking an internal coding region. These elements are less abundant in mammals compared to other class I transposable elements. About 8 percent of human genomic DNA comprises LTR retrotransposons. Some of the common examples of LTR retrotransposons are Ty elements in yeast and Copia elements in Drosophila.
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Related Experiment Video

Updated: Jul 10, 2025

Determining 3'-Termini and Sequences of Nascent Single-Stranded Viral DNA Molecules during HIV-1 Reverse Transcription in Infected Cells
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Targeting the Structural Maturation Pathway of HIV-1 Reverse Transcriptase.

Thomas W Kirby1, Scott A Gabel1, Eugene F DeRose1

  • 1Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, Durham, NC 27709, USA.

Biomolecules
|November 25, 2023
PubMed
Summary
This summary is machine-generated.

Researchers identified small molecules that interfere with HIV-1 reverse transcriptase (RT) dimerization. This approach targets the p51 subunit, offering a new strategy for developing antiviral therapies.

Keywords:
HIV-1 reverse transcriptaseRT dimerization inhibitorRT polymerase domainRT structural maturationground state stabilizationmaturation inhibitors

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Area of Science:

  • Biochemistry
  • Structural Biology
  • Drug Discovery

Background:

  • Active HIV-1 reverse transcriptase (RT) formation involves structural maturation and homodimerization.
  • Understanding this process is key to developing inhibitors that interfere with HIV-1 replication.

Purpose of the Study:

  • To identify small molecule ligands that inhibit the dimerization of HIV-1 RT.
  • To explore the p51 subunit as a target for drug development.

Main Methods:

  • Computational analysis to identify potential ligand binding sites at subdomain interfaces of the p51 subunit.
  • Screening and characterization of identified ligands using chromatography, NMR spectroscopy, and X-ray crystallography.
  • Evaluation of ligand-induced changes in the p51 homodimer/monomer ratio.

Main Results:

  • Identified ligands that bind near subdomain interfaces and to the fingers subdomain of p51.
  • Demonstrated that these ligands reduce p51 dimer formation.
  • Confirmed the feasibility of targeting solvent-accessible subunit interfaces in monomeric p51 and p66.

Conclusions:

  • The p51 subunit is a viable target for developing inhibitors of HIV-1 RT dimerization.
  • Ligands targeting these interfaces can interfere with RT maturation.
  • Further optimization is needed to enhance ligand binding affinity for potential therapeutic applications.