Role of SAMHD1 nuclear localization in restriction of HIV-1 and SIVmac

Alberto Brandariz-Nuñez, Jose C. Valle-Casuso, Tommy E. White, Nadine Laguette, Monsef Benkirane, Jurgen Brojatsch, Felipe Diaz-Griffero

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

Background: SAMHD1 is a nuclear protein that blocks lentiviral infection before reverse transcription in macrophages and dendritic cells. The viral accessory protein Vpx overcomes the SAMHD1-mediated lentiviral block by inducing its proteasomal degradation.Results: Here, we identified the nuclear localization signal (NLS) of SAMHD1, and studied its contribution to restriction of HIV-1 and SIVmac. By studying the cellular distribution of different SAMHD1 variants, we mapped the nuclear localization of SAMHD1 to residues 11KRPR14. Mutagenesis of these residues changed the cellular distribution of SAMHD1 from the nucleus to the cytoplasm. SAMHD1 mutants that lost nuclear localization restricted HIV-1 and SIV as potently as the wild type protein. Interestingly, SAMHD1 mutants that localized to the cytoplasm were not degraded by nuclear Vpx alleles. Therefore, nuclear Vpx alleles require nuclear localization of SAMHD1 in order to induce its degradation. In agreement, SIVmac viruses encoding Vpx did not overcome the restriction imposed by the cytoplasmic variants of SAMHD1.Conclusions: We mapped the NLS of SAMHD1 to residues 11KRPR14 and studied the contribution of SAMHD1 nuclear localization to restriction of HIV-1 and SIV. These experiments demonstrate that cytoplasmic variants of SAMHD1 potently block lentiviral infection and are resistant to Vpx-mediated degradation. The nuclear Vpx alleles studied here are only capable of degrading a nuclearly localized SAMHD1 suggesting that Vpx-mediated degradation of SAMHD1 is initiated in the nucleus.

Original languageEnglish (US)
Article number49
JournalRetrovirology
Volume9
DOIs
StatePublished - Jun 12 2012

Fingerprint

HIV-1
Nuclear Localization Signals
Alleles
Cytoplasm
Viral Regulatory and Accessory Proteins
Nuclear Proteins
Infection
Mutagenesis
Dendritic Cells
Reverse Transcription
Macrophages
Viruses
Proteins

Keywords

  • Degradation
  • HIV-1
  • Nuclear localization
  • Restriction
  • SAMHD
  • SIV
  • Vpx

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Brandariz-Nuñez, A., Valle-Casuso, J. C., White, T. E., Laguette, N., Benkirane, M., Brojatsch, J., & Diaz-Griffero, F. (2012). Role of SAMHD1 nuclear localization in restriction of HIV-1 and SIVmac. Retrovirology, 9, [49]. https://doi.org/10.1186/1742-4690-9-49

Role of SAMHD1 nuclear localization in restriction of HIV-1 and SIVmac. / Brandariz-Nuñez, Alberto; Valle-Casuso, Jose C.; White, Tommy E.; Laguette, Nadine; Benkirane, Monsef; Brojatsch, Jurgen; Diaz-Griffero, Felipe.

In: Retrovirology, Vol. 9, 49, 12.06.2012.

Research output: Contribution to journalArticle

Brandariz-Nuñez, A, Valle-Casuso, JC, White, TE, Laguette, N, Benkirane, M, Brojatsch, J & Diaz-Griffero, F 2012, 'Role of SAMHD1 nuclear localization in restriction of HIV-1 and SIVmac', Retrovirology, vol. 9, 49. https://doi.org/10.1186/1742-4690-9-49
Brandariz-Nuñez A, Valle-Casuso JC, White TE, Laguette N, Benkirane M, Brojatsch J et al. Role of SAMHD1 nuclear localization in restriction of HIV-1 and SIVmac. Retrovirology. 2012 Jun 12;9. 49. https://doi.org/10.1186/1742-4690-9-49
Brandariz-Nuñez, Alberto ; Valle-Casuso, Jose C. ; White, Tommy E. ; Laguette, Nadine ; Benkirane, Monsef ; Brojatsch, Jurgen ; Diaz-Griffero, Felipe. / Role of SAMHD1 nuclear localization in restriction of HIV-1 and SIVmac. In: Retrovirology. 2012 ; Vol. 9.
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