Identification of a nuclear transport inhibitory signal (NTIS) in the basic domain of HIV-I Vif protein

Assaf Friedler, Nehama Zakai, Orit Karni, Dorit Friedler, Chaim Gilon, Abraham Loyter*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

The HIV-1 auxiliary protein Vif contains a basic domain within its sequence. This basic region, 90RKKR93, is similar to the prototypic nuclear localization signal (NLS). However, Vif is not a nuclear protein and does not function in the nucleus. Here we have studied the karyophilic properties of this basic region. We have synthesized peptides corresponding to this positively charged NLS-like region and observed that these peptides inhibited nuclear transport via the importin pathway in vitro with IC50 values in the micromolar range. Inhibition was observed only with peptides derived from the positively charged region, but not from other regions of the Vif protein, showing sequence specificity. On the other hand, the Vif inhibitory peptide Vif88-98 did not confer karyophilic properties when conjugated to BSA. The inactive Vif conjugate and the active SV40-NLS-BSA conjugate both contained a similar number of peptides conjugated to each BSA molecule, as was determined by amino acid analysis of the peptide-BSA conjugates. Thus, the lack of nuclear import of the Vif peptide-BSA conjugate cannot be attributed to insufficient number of conjugated peptide molecules per BSA molecule. Our results suggest that the HIV-1 Vif protein carries an NLS-like sequence that inhibits, but does not mediate, nuclear import via the importin pathway. We have termed such signals as nuclear transport inhibitory signals (NTIS). The possible role of NTIS in controlling nuclear uptake, and specifically during virus infection, is discussed herein. Our results raise the possibility that NLS-like sequences of certain low molecular weight viral proteins may serve as regulators of nucleocytoplasmic trafficking and not as neccessarily as mediators of nuclear import.

Original languageAmerican English
Pages (from-to)431-437
Number of pages7
JournalJournal of Molecular Biology
Volume289
Issue number3
DOIs
StatePublished - 11 Jun 1999

Bibliographical note

Funding Information:
This work was supported by grants from the Wolfson Foundation for scientific research and from the Horowitz Investment Fund (for C.G. and A.L.) and by the DA'AT consortium (for C.G. and A.F.).

Keywords

  • HIV-1
  • NLS
  • Nuclear transport
  • Vif

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