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Publication Abstract from PubMed

HIV-1 reverse transcription initiates at the primer binding site (PBS) in the viral genomic RNA (gRNA). Although the structure of the PBS-segment undergoes substantial rearrangement upon tRNALys3 annealing, the proper folding of the PBS-segment during gRNA packaging is important as it ensures loading of beneficial host factors. DHX9/RNA helicase A (RHA) is recruited to gRNA to enhance the processivity of reverse transcriptase. Because the molecular details of the interactions have yet to be defined, we solved the solution structure of the PBS-segment preferentially bound by RHA. Evidence is provided that PBS-segment adopts a previously undefined adenosine-rich three-way junction structure encompassing the primer activation stem (PAS), tRNA-like element (TLE) and tRNA annealing arm. Disruption of the PBS-segment three-way junction structure diminished reverse transcription products and led to reduced viral infectivity. Because of the existence of the tRNA annealing arm, the TLE and PAS form a bent helical structure that undergoes shape-dependent recognition by RHA double-stranded RNA binding domain 1 (dsRBD1). Mutagenesis and phylogenetic analyses provide evidence for conservation of the PBS-segment three-way junction structure that is preferentially bound by RHA in support of efficient reverse transcription, the hallmark step of HIV-1 replication.

The three-way junction structure of the HIV-1 PBS-segment binds host enzyme important for viral infectivity.,Song Z, Gremminger T, Singh G, Cheng Y, Li J, Qiu L, Ji J, Lange MJ, Zuo X, Chen SJ, Zou X, Boris-Lawrie K, Heng X Nucleic Acids Res. 2021 May 12. pii: 6274540. doi: 10.1093/nar/gkab342. PMID:33978756^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.