Restriction of diverse retroviruses by SAMHD1

Thomas Gramberg, Tanja Kahle, Nicolin Bloch, Sabine Wittmann, Erik Müllers, Waaqo Daddacha, Henning Hofmann, Baek Kim, Dirk Lindemann, Nathaniel R. Landau

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

Background: SAMHD1 is a triphosphohydrolase that restricts the replication of HIV-1 and SIV in myeloid cells. In macrophages and dendritic cells, SAMHD1 restricts virus replication by diminishing the deoxynucleotide triphosphate pool to a level below that which supports lentiviral reverse transcription. HIV-2 and related SIVs encode the accessory protein Vpx to induce the proteasomal degradation of SAMHD1 following virus entry. While SAMHD1 has been shown to restrict HIV-1 and SIV, the breadth of its restriction is not known and whether other viruses have a means to counteract the restriction has not been determined.Results: We show that SAMHD1 restricts a wide array of divergent retroviruses, including the alpha, beta and gamma classes. Murine leukemia virus was restricted by SAMHD1 in macrophages yet removal of SAMHD1 did not alleviate the block to infection because of an additional block to viral nuclear import. Prototype foamy virus (PFV) and Human T cell leukemia virus type I (HTLV-1) were the only retroviruses tested that were not restricted by SAMHD1. PFV reverse transcribes predominantly prior to entry and thus is unaffected by the dNTP level in the target cell. It is possible that HTLV-1 has a mechanism to render the virus resistant to SAMHD1-mediated restriction.Conclusion: The results suggest that SAMHD1 has broad anti-retroviral activity against which most viruses have not found an escape.

Original languageEnglish (US)
Article number26
JournalRetrovirology
Volume10
Issue number1
DOIs
StatePublished - Mar 5 2013

Keywords

  • Accessory proteins
  • Dendritic cells
  • HIV
  • Macrophages
  • SAMHD1
  • Vpx

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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    Gramberg, T., Kahle, T., Bloch, N., Wittmann, S., Müllers, E., Daddacha, W., Hofmann, H., Kim, B., Lindemann, D., & Landau, N. R. (2013). Restriction of diverse retroviruses by SAMHD1. Retrovirology, 10(1), [26]. https://doi.org/10.1186/1742-4690-10-26