A cis-acting element in retroviral genomic RNA links Gag-Pol ribosomal frameshifting to selective viral RNA encapsidation.

Mastooreh Chamanian, Katarzyna J Purzycka, Paul T Wille, Janice S Ha, David McDonald, Yong Gao, Stuart F J Le Grice, Eric J Arts

Cell host & microbe 2013 Feb 13

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During retroviral RNA encapsidation, two full-length genomic (g) RNAs are selectively incorporated into assembling virions. Packaging involves a cis-acting packaging element (Ψ) within the 5' untranslated region of unspliced HIV-1 RNA genome. However, the mechanism(s) that selects and limits gRNAs for packaging remains uncertain. Using a dual complementation system involving bipartite HIV-1 gRNA, we observed that gRNA packaging is additionally dependent on a cis-acting RNA element, the genomic RNA packaging enhancer (GRPE), found within the gag p1-p6 domain and overlapping the Gag-Pol ribosomal frameshift signal. Deleting or disrupting the two conserved GRPE stem loops diminished gRNA packaging and infectivity >50-fold, while deleting gag sequences between Ψ and GRPE had no effect. Downregulating the translation termination factor eRF1 produces defective virus particles containing 20 times more gRNA. Thus, only the HIV-1 RNAs employed for Gag-Pol translation may be specifically selected for encapsidation, possibly explaining the limitation of two gRNAs per virion. Copyright © 2013 Elsevier Inc. All rights reserved.

Citation

Mastooreh Chamanian, Katarzyna J Purzycka, Paul T Wille, Janice S Ha, David McDonald, Yong Gao, Stuart F J Le Grice, Eric J Arts. A cis-acting element in retroviral genomic RNA links Gag-Pol ribosomal frameshifting to selective viral RNA encapsidation. Cell host & microbe. 2013 Feb 13;13(2):181-92