Functional analysis of the human immunodeficiency virus type 1 Rev protein oligomerization interface

Area of Science:

• Molecular Biology
• Virology
• Structural Biology

Background:

• Human Immunodeficiency Virus type 1 (HIV-1) structural protein expression depends on the viral trans-regulatory protein Rev.
• Rev functions as a nuclear shuttle protein, binding the Rev response element (RRE) RNA and facilitating cytoplasmic accumulation of viral mRNAs.
• Rev multimerization on the RRE is critical for HIV-1 replication, but the exact number of monomers required is unknown.

Purpose of the Study:

• To systematically analyze the multimerization domains within the Rev trans-activator protein.
• To identify specific amino acid residues involved in Rev intermolecular interactions.
• To investigate the role of Rev multimerization in HIV-1 replication.

Main Methods:

• Systematic analysis of Rev trans-activator protein domains.
• Identification of amino acid residues mediating intermolecular interactions within Rev.
• Expression of a multimerization-deficient Rev mutant to assess its effect on HIV-1 replication.

Main Results:

• Identified specific amino acid residues forming a hydrophobic surface patch in the Rev amino terminus responsible for intermolecular interactions.
• Demonstrated that these residues are critical for Rev multimerization.
• Showed that a multimerization-deficient Rev mutant inhibits HIV-1 replication in a dominant-negative manner.

Conclusions:

• The identified hydrophobic surface patch and its constituent residues are essential for Rev multimerization.
• Rev multimerization is indispensable for its trans-activation function and HIV-1 replication.
• Targeting Rev multimerization offers a potential strategy for inhibiting HIV-1 replication.