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Intermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC: novel insights into the regulation of Rev nuclear import.
Gu, Lili; Tsuji, Takahiro; Jarboui, Mohamed Ali; Yeo, Geok P; Sheehy, Noreen; Hall, William W; Gautier, Virginie W.
Affiliation
  • Gu L; UCD-Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin (UCD), Belfield, Dublin 4, Ireland.
Retrovirology ; 8: 17, 2011 Mar 14.
Article in En | MEDLINE | ID: mdl-21401918
ABSTRACT

BACKGROUND:

The HIV-1 regulatory protein Rev, which is essential for viral replication, mediates the nuclear export of unspliced viral transcripts. Rev nuclear function requires active nucleocytoplasmic shuttling, and Rev nuclear import is mediated by the recognition of its Nuclear Localisation Signal (NLS) by multiple import factors, which include transportin and importin ß. However, it remains unclear which nuclear import pathway(s) predominate in vivo, and the cellular environment that modulates Rev nucleocytoplasmic shuttling remains to be characterised.

RESULTS:

In our study, we have identified the cellular protein HIC (Human I-mfa domain-Containing protein) as a novel interactor of HIV-1 Rev. We demonstrate that HIC selectively interferes with Rev NLS interaction with importin ß and impedes its nuclear import and function, but does not affect Rev nuclear import mediated by transportin. Hence, the molecular determinants mediating Rev-NLS recognition by importin ß and transportin appear to be distinct. Furthermore, we have employed HIC and M9 M, a peptide specifically designed to inhibit the transportin-mediated nuclear import pathway, to characterise Rev nuclear import pathways within different cellular environments. Remarkably, we could show that in 293T, HeLa, COS7, Jurkat, U937, THP-1 and CEM cells, Rev nuclear import is cell type specific and alternatively mediated by transportin or importin ß, in a mutually exclusive fashion.

CONCLUSIONS:

Rev cytoplasmic sequestration by HIC may represent a novel mechanism for the control of Rev function. These studies highlight that the multivalent nature of the Rev NLS for different import receptors enables Rev to adapt its nuclear trafficking strategy.
Subject(s)

Full text: 1 Database: MEDLINE Main subject: Gene Expression Regulation, Viral / Cell Nucleus / HIV-1 / Myogenic Regulatory Factors / Nuclear Localization Signals / Rev Gene Products, Human Immunodeficiency Virus Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Retrovirology Journal subject: VIROLOGIA Year: 2011 Type: Article Affiliation country: Ireland

Full text: 1 Database: MEDLINE Main subject: Gene Expression Regulation, Viral / Cell Nucleus / HIV-1 / Myogenic Regulatory Factors / Nuclear Localization Signals / Rev Gene Products, Human Immunodeficiency Virus Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Retrovirology Journal subject: VIROLOGIA Year: 2011 Type: Article Affiliation country: Ireland