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A Restriction Enzyme Based Cloning Method to Assess the In vitro Replication Capacity of HIV-1 Subtype C Gag-MJ4 Chimeric Viruses
Published on: August 31, 2014
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Mutagenic Analysis of the HIV Restriction Factor Shiftless.
Niklas Jäger1,2, Shreya Ahana Ayyub3, Natalia Korniy3
1Infection Biology Unit, German Primate Center, 37077 Göttingen, Germany.
Viruses
|July 27, 2022
Summary
The shiftless (SFL) protein inhibits human immunodeficiency virus (HIV) by blocking ribosomal frameshifting. This action requires a specific RAA region, crucial for SFL binding to HIV RNA and blocking viral replication.
Area of Science:
- Virology
- Molecular Biology
- Host-Pathogen Interactions
Background:
- The interferon-induced host cell protein shiftless (SFL) inhibits human immunodeficiency virus (HIV) by blocking -1 programmed ribosomal frameshifting (-1PRF).
- The precise mechanism by which SFL inhibits -1PRF remains unclear.
- A 36-amino acid region, termed required for antiviral activity (RAA), is essential for SFL's function but absent in the SFL short (SFLS) splice variant.
Purpose of the Study:
- To elucidate the mechanism by which SFL inhibits HIV -1PRF.
- To investigate the role of the RAA region in SFL's antiviral activity.
- To characterize the function of the SFLS splice variant.
Main Methods:
- Comparative analysis of SFL and SFLS activity against HIV -1PRF.
- Mutagenic analysis of the RAA region in SFL.
- Biochemical assays to assess SFL self-interactions, ribosome association, and binding to HIV RNA.
Main Results:
- SFL, but not SFLS, inhibits HIV -1PRF in a cell-type-independent manner.
- The RAA region is essential for SFL self-interactions, ribosome association, and binding to HIV RNA.
- Deletions within the RAA region impair SFL's ability to bind HIV RNA, inhibit -1PRF, suppress Gag-Pol expression, and confer antiviral activity.
Conclusions:
- SFL inhibits HIV -1PRF and infection by directly binding to the ribosome and HIV RNA.
- The RAA region is critical for SFL's mechanism of action.
- SFL multimerization may play a functional role in its antiviral activity.
