Contribution of SAM and HD domains to retroviral restriction mediated by human SAMHD1

Tommy E. White, Alberto Brandariz-Nuñez, Jose Carlos Valle-Casuso, Sarah Amie, Laura Nguyen, Baek Kim, Jurgen Brojatsch, Felipe Diaz-Griffero

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

The human SAMHD1 protein is a novel retroviral restriction factor expressed in myeloid cells. Previous work has correlated the deoxynucleotide triphosphohydrolase activity of SAMHD1 with its ability to block HIV-1 and SIVmac infection. SAMHD1 is comprised of the sterile alpha motif (SAM) and histidine-aspartic (HD) domains; however the contribution of these domains to retroviral restriction is not understood. Mutagenesis and deletion studies revealed that expression of the sole HD domain of SAMHD1 is sufficient to achieve potent restriction of HIV-1 and SIVmac. We demonstrated that the HD domain of SAMHD1 is essential for the ability of SAMHD1 to oligomerize by using a biochemical assay. In agreement with previous observations, we mapped the RNA-binding ability of SAMHD1 to the HD domain. We also demonstrated a direct interaction of SAMHD1 with RNA by using enzymatically-active purified SAMHD1 protein from insect cells. Interestingly, we showed that double-stranded RNA inhibits the enzymatic activity of SAMHD1 in vitro suggesting the possibility that RNA from a pathogen might modulate the enzymatic activity of SAMHD1 in cells. By contrast, we found that the SAM domain is dispensable for retroviral restriction, oligomerization and RNA binding. Finally we tested the ability of SAMHD1 to block the infection of retroviruses other than HIV-1 and SIVmac. These results showed that SAMHD1 blocks infection of HIV-2, feline immunodeficiency virus (FIV), bovine immunodeficiency virus (BIV), Equine infectious anemia virus (EIAV), N-tropic murine leukemia virus (N-MLV), and B-tropic murine leukemia virus (B-MLV).

Original languageEnglish (US)
Pages (from-to)81-90
Number of pages10
JournalVirology
Volume436
Issue number1
DOIs
StatePublished - Feb 5 2013

Fingerprint

Histidine
RNA
HIV-1
Murine Leukemia Viruses
Bovine Immunodeficiency Virus
Equine infectious anemia virus
Insect Proteins
Retroviridae Infections
Feline Immunodeficiency Virus
HIV-2
Double-Stranded RNA
Myeloid Cells
Infection
Mutagenesis
Sterile Alpha Motif

Keywords

  • DNTPase
  • HD domain
  • HIV-1
  • Restriction
  • RNA binding
  • SAMHD1

ASJC Scopus subject areas

  • Virology

Cite this

White, T. E., Brandariz-Nuñez, A., Carlos Valle-Casuso, J., Amie, S., Nguyen, L., Kim, B., ... Diaz-Griffero, F. (2013). Contribution of SAM and HD domains to retroviral restriction mediated by human SAMHD1. Virology, 436(1), 81-90. https://doi.org/10.1016/j.virol.2012.10.029

Contribution of SAM and HD domains to retroviral restriction mediated by human SAMHD1. / White, Tommy E.; Brandariz-Nuñez, Alberto; Carlos Valle-Casuso, Jose; Amie, Sarah; Nguyen, Laura; Kim, Baek; Brojatsch, Jurgen; Diaz-Griffero, Felipe.

In: Virology, Vol. 436, No. 1, 05.02.2013, p. 81-90.

Research output: Contribution to journalArticle

White, TE, Brandariz-Nuñez, A, Carlos Valle-Casuso, J, Amie, S, Nguyen, L, Kim, B, Brojatsch, J & Diaz-Griffero, F 2013, 'Contribution of SAM and HD domains to retroviral restriction mediated by human SAMHD1', Virology, vol. 436, no. 1, pp. 81-90. https://doi.org/10.1016/j.virol.2012.10.029
White TE, Brandariz-Nuñez A, Carlos Valle-Casuso J, Amie S, Nguyen L, Kim B et al. Contribution of SAM and HD domains to retroviral restriction mediated by human SAMHD1. Virology. 2013 Feb 5;436(1):81-90. https://doi.org/10.1016/j.virol.2012.10.029
White, Tommy E. ; Brandariz-Nuñez, Alberto ; Carlos Valle-Casuso, Jose ; Amie, Sarah ; Nguyen, Laura ; Kim, Baek ; Brojatsch, Jurgen ; Diaz-Griffero, Felipe. / Contribution of SAM and HD domains to retroviral restriction mediated by human SAMHD1. In: Virology. 2013 ; Vol. 436, No. 1. pp. 81-90.
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