HIV-1 RNA dimerization: It takes two to tango

Abstract

Each viral particle of HIV-1, the infectious agent of AIDS, contains two copies of the full-length viral genomic RNA. Encapsidating two copies of genomic RNA is one of the characteristics of the retrovirus family. The two RNA molecules are both positive-sense and often identical; furthermore, each RNA encodes the full complement of genetic information required for viral replication. The two strands of RNA are intricately entwined within the core of the mature infectious virus as a ribonuclear complex with the viral proteins, including nucleocapsid. Multiple steps in the biogenesis of the genomic full-length RNA are involved in achieving this location and dimeric state. The viral sequences and proteins involved in the process of RNA dimerization, both for the initial interstrand contact and subsequent steps that result in the condensed, stable conformation of the genomic RNA, are outlined in this review. In addition, the impact of the dimeric state of HIV-1 viral RNA is discussed with respect to its importance in efficient viral replication and, consequently, the potential development of antiviral strategies designed to disrupt the formation of dimeric RNA.

Figure 1

RNA sequences and conformation at the 5′ end of the HIV-1 genome. Nucleotide sequences are based on the HIV-1_HXB2 RNA transcript and the first base is marked +1; nt 100, 200, and 300 are marked. The palindromic sequences proposed to pair with the counterpart palindrome of the RNA partner are marked by solid lines, whereas sequences in the originally proposed SL4 are marked by dashes. The refined dimer linkage structure sequence by Suguraki, et al. is shown in boldface. TAR: transactivation response element; PBS: primer binding site; SL: stem loop.

Figure 2

Proposed interactions between stem loop 1 (SL1) of two RNA molecules for dimerization. The palindromic sequences in two dimerization initiation site (DIS) regions form base-pairing to generate a kissing loop complex. Base-pairing could proceed down the SL1 stem to form the extended dimer.