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Determining 3'-Termini and Sequences of Nascent Single-Stranded Viral DNA Molecules during HIV-1 Reverse Transcription in Infected Cells
Published on: January 30, 2019
Human cytidine deaminase APOBEC3H restricts HIV-1 replication
Ying Dang1, Lai Mun Siew, Xiaojun Wang
1Department of Microbiology & Molecular Genetics, College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan 48824-4320, USA.
The Journal of Biological Chemistry
|February 27, 2008
Summary
APOBEC3H (A3H) shows potent antiretroviral activity against HIV-1 by a novel mechanism. Restoring A3H expression offers a promising therapeutic strategy for HIV-1 treatment.
Area of Science:
- Molecular Biology
- Virology
- Immunology
Background:
- The human genome contains seven APOBEC3 (A3) cytidine deaminases with antiretroviral potential.
- APOBEC3G (A3G) was the first identified to inhibit human immunodeficiency virus type 1 (HIV-1) replication.
- HIV-1 Vif protein neutralizes several A3 proteins, but A3H's activity remained undefined due to poor expression.
Purpose of the Study:
- To investigate the mechanism hindering APOBEC3H (A3H) expression.
- To determine the antiretroviral activity of A3H and its susceptibility to HIV-1 Vif.
- To explore A3H as a potential therapeutic target for HIV-1.
Main Methods:
- Comparative sequence analysis of primate A3H genes to identify expression impediments.
- Functional assays to assess A3H's impact on HIV-1 infectivity and Vif interaction.
- Gene expression optimization strategies, including sequence repair and vector-based expression.
Main Results:
- A premature termination codon in human and chimpanzee A3H genes significantly reduces protein expression.
- Optimized A3H expression inhibited HIV-1 infectivity up to 150-fold.
- HIV-1 Vif could not neutralize A3H, and A3H inhibited HIV-1 replication independently of cytidine deamination.
Conclusions:
- A3H possesses potent, Vif-resistant antiretroviral activity through a non-canonical mechanism.
- Restoring or enhancing A3H expression is a viable therapeutic strategy against HIV-1.
- Further research into A3H's unique inhibitory mechanism could yield novel antiviral therapies.
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