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Evaluation of the Efficacy And Toxicity of RNAs Targeting HIV-1 Production for Use in Gene or Drug Therapy
Published on: September 5, 2016
A functional role for ADAM10 in human immunodeficiency virus type-1 replication.
Brian M Friedrich1, James L Murray, Guangyu Li
1Department of Pathology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, USA.
Retrovirology
|May 17, 2011
Summary
A Disintegrin and Metalloprotease 10 (ADAM10) is crucial for HIV-1 replication by aiding nuclear trafficking. Targeting ADAM10 offers a new strategy for developing antiviral drugs.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Gene trap insertional mutagenesis identified cellular genes involved in viral infection.
- A Disintegrin and Metalloprotease 10 (ADAM10) was found to be essential for Human Immunodeficiency Virus type 1 (HIV-1) replication.
Purpose of the Study:
- To investigate the role of ADAM10 in HIV-1 replication.
- To elucidate the mechanism by which ADAM10 influences viral replication.
- To identify ADAM10 as a potential therapeutic target for HIV-1 infection.
Main Methods:
- Small interfering RNA (siRNA) was used to silence ADAM10 expression.
- HIV-1 replication was assessed in primary human monocyte-derived macrophages and CD4+ cell lines.
- Viral reverse transcription, integration, and downstream gene expression were analyzed.
Main Results:
- ADAM10 silencing significantly inhibited HIV-1 replication, while its overexpression enhanced it.
- ADAM10 is not required for viral entry, uncoating, or reverse transcription.
- ADAM10 down-regulation reduced viral cDNA integration and inhibited downstream reporter gene expression and protein translation, suggesting a role in nuclear trafficking.
Conclusions:
- ADAM10 facilitates HIV-1 replication, likely at the nuclear trafficking stage.
- Cleavage of ADAM10 by ADAM15 and γ-secretase is important for its function in viral replication.
- ADAM10 represents a novel cellular target for the development of antiretroviral drugs.
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