کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2044695 1073431 2008 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Transportin-SR2 Imports HIV into the Nucleus
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم کشاورزی و بیولوژیک (عمومی)
پیش نمایش صفحه اول مقاله
Transportin-SR2 Imports HIV into the Nucleus
چکیده انگلیسی

SummaryBackgroundThe human immunodeficiency virus type 1 (HIV-1) and other lentiviruses have the capacity to infect nondividing cells like macrophages. This requires import of the preintegration complex (PIC) through the nuclear pore. Although many cellular and viral determinants have been proposed, the mechanism leading to nuclear import is not yet understood.ResultsUsing yeast two-hybrid and pull-down, we identified and validated transportin-SR2 (TRN-SR2) as a bona fide binding partner of HIV-1 integrase. We confirmed the biological relevance of this interaction by RNAi. Depletion of TRN-SR2 interfered with the replication of HIV-1 and HIV-2 but not MoMLV in HeLaP4 cells. Knockdown of TRN-SR2 in primary macrophages likewise interfered with HIV-1 replication. Using Q-PCR, we pinpoint this block in replication to the early steps of the viral lifecycle. A reduction in 2-LTR formation suggests a block in PIC nuclear import upon siRNA-mediated knockdown. Different lines of evidence clearly proved that the late steps of viral replication are not affected. In an in vivo nuclear-import assay using labeled HIV-1 particles, the defect in nuclear import after depletion of TRN-SR2 was directly visualized. In comparison with control cell lines, the great majority of siRNA-treated cells did not contain any PIC in the nucleus.ConclusionOur data clearly demonstrate that TRN-SR2 is the nuclear-import factor of HIV.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 18, Issue 16, 26 August 2008, Pages 1192–1202
نویسندگان
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