The three-way junction structure of the HIV-1 PBS-segment binds host enzyme important for viral infectivity

Zhenwei Song, Thomas Gremminger, Gatikrushna Singh, Yi Cheng, Jun Li, Liming Qiu, Juan Ji, Margaret J. Lange, Xiaobing Zuo, Shi Jie Chen, Xiaoqin Zou, Kathleen Boris-Lawrie, Xiao Heng

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5925-5942
Number of pages18
JournalNucleic acids research
Volume49
Issue number10
DOIs
StatePublished - Jun 4 2021

Bibliographical note

Publisher Copyright:
© 2021 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research.

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