Functional equivalence of retroviral MA domains in facilitating Psi RNA binding specificity by Gag

Tiffiny Rye-McCurdy, Erik D. Olson, Shuohui Liu, Christiana Binkley, Joshua Paolo Reyes, Brian R. Thompson, John M. Flanagan, Leslie J. Parent, Karin Musier-Forsyth

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7 Scopus citations

Abstract

Retroviruses specifically package full-length, dimeric genomic RNA (gRNA) even in the presence of a vast excess of cellular RNA. The “psi” (ψ) element within the 5ʹ-untranslated region (5ʹUTR) of gRNA is critical for packaging through interaction with the nucleocapsid (NC) domain of Gag. However, in vitro Gag binding affinity for ψ versus non-ψ RNAs is not significantly different. Previous salt-titration binding assays revealed that human immunodeficiency virus type 1 (HIV-1) Gag bound to ψ RNA with high specificity and relatively few charge interactions, whereas binding to non-ψ RNA was less specific and involved more electrostatic interactions. The NC domain was critical for specific ψ binding, but surprisingly, a Gag mutant lacking the matrix (MA) domain was less effective at discriminating ψ from non-ψ RNA. We now find that Rous sarcoma virus (RSV) Gag also effectively discriminates RSV ψ from non-ψ RNA in a MA-dependent manner. Interestingly, Gag chimeras, wherein the HIV-1 and RSV MA domains were swapped, maintained high binding specificity to cognate ψ RNAs. Using ψ RNA mutant constructs, determinants responsible for promoting high Gag binding specificity were identified in both systems. Taken together, these studies reveal the functional equivalence of HIV-1 and RSV MA domains in facilitating ψ RNA selectivity by Gag, as well as ψ elements that promote this selectivity.

Original languageEnglish (US)
Article number256
JournalViruses
Volume8
Issue number9
DOIs
StatePublished - Sep 20 2016

All Science Journal Classification (ASJC) codes

  • Infectious Diseases
  • Virology

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    Rye-McCurdy, T., Olson, E. D., Liu, S., Binkley, C., Reyes, J. P., Thompson, B. R., Flanagan, J. M., Parent, L. J., & Musier-Forsyth, K. (2016). Functional equivalence of retroviral MA domains in facilitating Psi RNA binding specificity by Gag. Viruses, 8(9), [256]. https://doi.org/10.3390/v8090256