Degradation of SAMHD1 by Vpx Is Independent of Uncoating

Journal of Virology
Paula JáureguiN R Landau

Abstract

Sterile alpha motif domain and HD domain-containing protein 1 (SAMHD1) restricts human immunodeficiency virus type 1 (HIV-1) replication in myeloid and resting T cells. Lentiviruses such as HIV-2 and some simian immunodeficiency viruses (SIVs) counteract the restriction by encoding Vpx or Vpr, accessory proteins that are packaged in virions and which, upon entry of the virus into the cytoplasm, induce the proteasomal degradation of SAMHD1. As a tool to study these mechanisms, we generated HeLa cell lines that express a fusion protein termed NLS.GFP.SAM595 in which the Vpx binding domain of SAMHD1 is fused to the carboxy terminus of green fluorescent protein (GFP) and a nuclear localization signal is fused to the amino terminus of GFP. Upon incubation of Vpx-containing virions with the cells, the NLS.GFP.SAM595 fusion protein was degraded over several hours and the levels remained low over 5 days as the result of continued targeting of the CRL4 E3 ubiquitin ligase. Degradation of the fusion protein required that it contain a nuclear localization sequence. Fusion to the cytoplasmic protein muNS rendered the protein resistant to Vpx-mediated degradation, confirming that SAMHD1 is targeted in the nucleus. Virions treated with prote...Continue Reading

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Citations

Mar 9, 2018·Scientific Reports·Paula Jáuregui, Nathaniel R Landau
May 20, 2015·Nature Immunology·Viviana SimonNathaniel R Landau
Dec 18, 2019·Proceedings of the National Academy of Sciences of the United States of America·Rosa M Rubio, Ian Mohr
Nov 24, 2020·Frontiers in Immunology·Wilfried PoschDoris Wilflingseder

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