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cis-acting sequences involved in human immunodeficiency virus type 1 RNA packaging
J F Kaye1, J H Richardson, A M Lever
1Department of Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom.
Journal of Virology
|October 1, 1995
Summary
Human immunodeficiency virus type 1 (HIV-1) vector RNA packaging is not essential for the Rev-responsive element (RRE) or env sequences. However, their removal significantly reduces vector transduction efficiency.
Area of Science:
- Molecular Biology
- Virology
- Gene Therapy
Background:
- Human immunodeficiency virus type 1 (HIV-1)-based vectors are utilized for gene delivery.
- Efficient RNA encapsidation in these vectors was previously linked to an env gene fragment containing the Rev-responsive element (RRE).
Purpose of the Study:
- To investigate the specific roles of the RRE and adjacent env sequences in HIV-1 vector expression and RNA encapsidation.
- To determine if these elements are essential for vector packaging and transduction.
Main Methods:
- Construction and analysis of a series of HIV-1-based vectors with deletions within the env gene fragment.
- Assessment of RNA encapsidation efficiency and vector transduction titers.
Main Results:
- Deletion analysis did not identify a discrete packaging signal within the env fragment, though some deletions reduced packaging efficiency.
- Complete removal of the env fragment drastically decreased transduction titers (100-fold) but did not eliminate RNA encapsidation.
- The RRE and 3' env sequences are not essential for HIV-1 vector encapsidation.
Conclusions:
- The RRE and 3' env sequences are not critical for HIV-1 vector RNA encapsidation.
- These sequences may play a role in maintaining the structure of the 5' packaging signal when heterologous genes are present, thereby influencing vector performance.