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Updated: Feb 6, 2026
10:49
In vitro Uncoating of HIV-1 Cores
Published on: November 8, 2011
16.3K
HIV-1 Vpr and p21 restrict LINE-1 mobility
Koudai Kawano1, Aurélien J Doucet2, Mikinori Ueno1
1Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan.
Nucleic Acids Research
|August 8, 2018
Summary
Human immunodeficiency virus type 1 (HIV-1) suppresses Long Interspersed Element-1 (L1) retrotransposition. Viral protein Vpr and host cell cycle regulators like p21 inhibit L1 mobility via cell cycle-dependent mechanisms.
Area of Science:
- Genetics
- Molecular Biology
- Virology
Background:
- Long Interspersed Element-1 (LINE-1, L1) constitutes a significant portion of the human genome.
- The genetic interplay between L1 elements and human immunodeficiency virus type 1 (HIV-1) is not well understood.
Purpose of the Study:
- To investigate the mechanisms by which HIV-1 influences L1 retrotransposition.
- To determine if HIV-1 Vpr protein regulates L1 mobility in a cell cycle-dependent manner.
- To identify host cell cycle regulators involved in suppressing L1 retrotransposition.
Main Methods:
- Assessing L1 retrotransposition rates in the presence of HIV-1 components.
- Utilizing mutant Vpr (H71R) to evaluate cell cycle arrest dependency.
- Investigating the role of host cell cycle regulators p21Waf1 and p27Kip1.
- Performing co-immunoprecipitation assays with L1 ORF2p.
- Conducting LEAP assays to measure L1 reverse transcriptase activity.
Main Results:
- HIV-1 significantly suppresses L1 retrotransposition.
- HIV-1 Vpr inhibits L1 retrotransposition independently of L1 promoter activity, in a cell cycle-dependent manner.
- Host cell cycle regulators p21Waf1 and p27Kip1 strongly inhibit L1 retrotransposition.
- Vpr and p21 interact with L1 ORF2p and inhibit its reverse transcriptase activity.
Conclusions:
- Viral (HIV-1 Vpr) and host cell cycle regulatory pathways converge to limit L1 retrotransposition.
- Vpr and host factors like p21 suppress L1 mobility by inhibiting ORF2p-mediated reverse transcription.
- Cell cycle regulation plays a crucial role in controlling the activity of mobile genetic elements like L1.
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