Conditional regulatory elements of human immunodeficiency virus type 2 long terminal repeat

Area of Science:

• Virology
• Molecular Biology
• Genetics

Background:

• The human immunodeficiency virus type 2 (HIV-2) long terminal repeat (LTR) is crucial for viral gene expression and replication.
• Understanding the regulatory mechanisms of HIV-2 LTR is essential for developing antiviral strategies.

Purpose of the Study:

• To identify and characterize novel cis-acting regulatory elements within the HIV-2 LTR.
• To investigate the cell type-specific activity of these elements and their interaction with viral proteins like Tat.

Main Methods:

• Mutational analysis of the HIV-2 LTR U3 region.
• Reporter gene assays in various human cell lines (CEM, Jurkat, U937, HeLa).
• Assessment of Tat-mediated trans-activation and T cell activation responses.

Main Results:

• A novel positive and a negative regulatory element were identified in the upstream U3 region of the HIV-2 LTR.
• These elements exhibited cell type-specific activity, with varying effects in lymphocytic, monocytic, and epithelioid cells.
• The negative regulatory element's effect was abrogated by HIV-2 Tat, indicating its role in Tat-mediated trans-activation.
• T cell activation signals were also mapped to the upstream U3 region.
• The impact of these regulatory elements was dependent on the basal LTR activity, which itself was cell type-specific.

Conclusions:

• The HIV-2 LTR contains cell type-specific regulatory elements in the U3 region that influence viral gene expression.
• These findings highlight the importance of cell-specific transcriptional factors in regulating HIV-2 replication.
• The identified elements and their interactions with Tat may contribute to the cell type-specific restriction of HIV-2 replication in vivo.