A proposal for a new HIV-1 DLS structural model.
The dimer initiation site/dimer linkage sequence (DIS/DLS) region of the human immunodeficiency virus type 1 (HIV-1) RNA genome is suggested to play essential roles at various stages of the viral life cycle. Through a novel assay we had recently developed, we reported on the necessary and sufficient region for RNA dimerization in the HIV-1 virion. Using this system, we performed further detailed mapping of the functional base pairs necessary for HIV-1 DLS structure. Interestingly, the study revealed a previously unnoticed stem formation between two distantly positioned regions. Based on this and other findings on functional base pairing in vivo, we propose new 3D models of the HIV-1 DLS which contain a unique pseudoknot-like conformation. Since this pseudoknot-like conformation appears to be thermodynamically stable, forms a foundational skeleton for the DLS and sterically restricts the spontaneous diversification of DLS conformations, its unique shape may contribute to the viral life cycle and potentially serve as a novel target for anti-HIV-1 therapies.
Department of Viral Infections, RIMD, Osaka Univ. 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. sakuragi@biken.osaka-u.ac.jp
Jun-ichi
J
Sakuragi
Hirotaka
H
Ode
Sayuri
S
Sakuragi
Tatsuo
T
Shioda
Hironori
H
Sato
D001483:Base Sequence; D003198:Computer Simulation; D019281:Dimerization; D057809:HEK293 Cells; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012367:RNA, Viral / Q000737:chemistry*; D014779:Virus Replication
D012367:RNA, Viral