Host SAMHD1 protein promotes HIV-1 recombination in macrophages.

The Journal of Biological Chemistry
Laura A NguyenBaek Kim

Abstract

Template switching can occur during the reverse transcription of HIV-1. Deoxynucleotide triphosphate (dNTP) concentrations have been biochemically shown to impact HIV-1 reverse transcriptase (RT)-mediated strand transfer. Lowering the dNTP concentrations promotes RT pausing and RNA template degradation by RNase H activity of the RT, subsequently leading to strand transfer. Terminally differentiated/nondividing macrophages, which serve as a key HIV-1 reservoir, contain extremely low dNTP concentrations (20-50 nm), which results from the cellular dNTP hydrolyzing sterile α motif and histidine aspartic domain containing protein 1 (SAMHD1) protein, when compared with activated CD4(+) T cells (2-5 μm). In this study, we first observed that HIV-1 template switching efficiency was nearly doubled in human primary macrophages when compared with activated CD4(+) T cells. Second, SAMHD1 degradation by viral protein X (Vpx), which elevates cellular dNTP concentrations, decreased HIV-1 template switching efficiency in macrophages to the levels comparable with CD4(+) T cells. Third, differentiated SAMHD1 shRNA THP-1 cells have a 2-fold increase in HIV-1 template switching efficiency. Fourth, SAMHD1 degradation by Vpx did not alter HIV-1 temp...Continue Reading

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Citations

Aug 12, 2014·The Journal of General Virology·Lauren B BeachLouis M Mansky
Oct 25, 2017·Viral Immunology·Mahmoud Mohammad YaseenMohammad Mahmoud Yaseen
Jan 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Elisa FranzolinChiara Rampazzo
Dec 23, 2015·AIDS·Deborah CromerMiles P Davenport

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