Virus Genes. 2010 Jun;40(3):341-6. Epub 2010 Feb 12.

Over-expression of the HIV-1 Rev promotes death of nondividing eukaryotic cells.

Levin A, Hayouka Z, Friedler A, Loyter A.

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Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.

Abstract

Expression of the human immunodeficiency virus type 1 (HIV-1) Rev protein is essential for completion of the viral life cycle. Rev mediates nuclear export of partially spliced and unspliced viral transcripts and therefore bears a nuclear localization signal (NLS) as well as a nuclear export signal (NES), which allow its nucleocytoplasmic shuttling. Attempts to express the wild-type Rev protein in eukaryotic human cultured cells have encountered difficulties and so far have failed. Here we show that accumulation of Rev, which occurs in nondividing Rev-expressing cells or when such cells reach confluency, results in death of these cells. Cell death was also promoted by addition of a cell permeable peptide bearing the Rev-NES sequence, but not by the Rev-NLS peptide. Our results probably indicate that binding of excess amounts of the Rev protein or the NES peptide to the exportin receptor CRM1 results in cells' death.

PMID:: 20151187; [PubMed - indexed for MEDLINE]

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Inhibition of human immunodeficiency virus Rev and human T-cell leukemia virus Rex function, but not Mason-Pfizer monkey virus constitutive transport element activity, by a mutant human nucleoporin targeted to Crm1. [J Virol. 1998]
Inhibition of human immunodeficiency virus Rev and human T-cell leukemia virus Rex function, but not Mason-Pfizer monkey virus constitutive transport element activity, by a mutant human nucleoporin targeted to Crm1.
Bogerd HP, Echarri A, Ross TM, Cullen BR. J Virol. 1998 Nov; 72(11):8627-35.
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Daelemans D, Afonina E, Nilsson J, Werner G, Kjems J, De Clercq E, Pavlakis GN, Vandamme AM. Proc Natl Acad Sci U S A. 2002 Oct 29; 99(22):14440-5. Epub 2002 Oct 9.
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Review [HIV-1 Rev and related inhibitors].
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Cited by 3 PubMed Central articles

Transportin 3 and importin α are required for effective nuclear import of HIV-1 integrase in virus-infected cells. [Nucleus. 2010]
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Levin A, Hayouka Z, Friedler A, Loyter A. Nucleus. 2010 Sep-Oct; 1(5):422-31.
Specific eradication of HIV-1 from infected cultured cells. [AIDS Res Ther. 2010]
Specific eradication of HIV-1 from infected cultured cells.
Levin A, Hayouka Z, Friedler A, Loyter A. AIDS Res Ther. 2010 Aug 19; 7:31. Epub 2010 Aug 19.
Peptides derived from the HIV-1 integrase promote HIV-1 infection and multi-integration of viral cDNA in LEDGF/p75-knockdown cells. [Virol J. 2010]
Peptides derived from the HIV-1 integrase promote HIV-1 infection and multi-integration of viral cDNA in LEDGF/p75-knockdown cells.
Levin A, Hayouka Z, Friedler A, Loyter A. Virol J. 2010 Aug 2; 7:177. Epub 2010 Aug 2.

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