Human T-cell leukemia virus type 1 Gag domains have distinct RNA-binding specificities with implications for RNA packaging and dimerization

Weixin Wu, Joshua Hatterschide, Yu Ci Syu, William A. Cantara, Ruth J. Blower, Heather M. Hanson, Louis M Mansky, Karin Musier-Forsyth

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Abstract

Human T-cell leukemia virus type 1 (HTLV-1) is the first retrovirus that has conclusively been shown to cause human diseases. In HIV-1, specific interactions between the nucleocapsid (NC) domain of the Gag protein and genomic RNA (gRNA) mediate gRNA dimerization and selective packaging; however, the mechanism for gRNA packaging in HTLV-1, a deltaretrovirus, is unclear. In other deltaretroviruses, the matrix (MA) and NC domains of Gag are both involved in gRNA packaging, but MA binds nucleic acids with higher affinity and has more robust chaperone activity, suggesting that this domain may play a primary role. Here, we show that the MA domain of HTLV-1, but not the NC domain, binds short hairpin RNAs derived from the putative gRNA packaging signal. RNA probing of the HTLV-1 5 leader and cross-linking studies revealed that the primer-binding site and a region within the putative packaging signal form stable hairpins that interact with MA. In addition to a previously identified palindromic dimerization initiation site (DIS), we identified anewDISinHTLV-1gRNA andfoundthatbothpalindromic sequences bind specificallytheNC domain. Surprisingly, a mutant partially defective in dimer formation in vitro exhibited a significant increase in RNA packaging into HTLV-1-like particles, suggesting that efficient RNA dimerization may not be strictly required for RNA packaging in HTLV-1. Moreover, the lifecycle of HTLV-1 and other deltaretroviruses may be characterized by NC and MA functions that are distinct from those of the corresponding HIV-1 proteins, but together provide the functions required for viral replication.

Original languageEnglish (US)
Pages (from-to)16261-16276
Number of pages16
JournalJournal of Biological Chemistry
Volume293
Issue number42
DOIs
StatePublished - Jan 1 2018

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Deltaretrovirus
T-cells
Dimerization
Product Packaging
Viruses
Packaging
RNA
Nucleocapsid
HIV-1
gag Gene Products
Human Immunodeficiency Virus Proteins
Retroviridae
Dimers
Nucleic Acids
Small Interfering RNA
Binding Sites

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Cite this

Wu, W., Hatterschide, J., Syu, Y. C., Cantara, W. A., Blower, R. J., Hanson, H. M., ... Musier-Forsyth, K. (2018). Human T-cell leukemia virus type 1 Gag domains have distinct RNA-binding specificities with implications for RNA packaging and dimerization. Journal of Biological Chemistry, 293(42), 16261-16276. https://doi.org/10.1074/jbc.RA118.005531

Human T-cell leukemia virus type 1 Gag domains have distinct RNA-binding specificities with implications for RNA packaging and dimerization. / Wu, Weixin; Hatterschide, Joshua; Syu, Yu Ci; Cantara, William A.; Blower, Ruth J.; Hanson, Heather M.; Mansky, Louis M; Musier-Forsyth, Karin.

In: Journal of Biological Chemistry, Vol. 293, No. 42, 01.01.2018, p. 16261-16276.

Research output: Contribution to journalArticle

Wu, Weixin ; Hatterschide, Joshua ; Syu, Yu Ci ; Cantara, William A. ; Blower, Ruth J. ; Hanson, Heather M. ; Mansky, Louis M ; Musier-Forsyth, Karin. / Human T-cell leukemia virus type 1 Gag domains have distinct RNA-binding specificities with implications for RNA packaging and dimerization. In: Journal of Biological Chemistry. 2018 ; Vol. 293, No. 42. pp. 16261-16276.
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