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Open Access Highly Accessed Research

Restriction of diverse retroviruses by SAMHD1

Thomas Gramberg12*, Tanja Kahle2, Nicolin Bloch1, Sabine Wittmann2, Erik Müllers3, Waaqo Daddacha4, Henning Hofmann1, Baek Kim4, Dirk Lindemann3 and Nathaniel R Landau1*

Author Affiliations

1 Microbiology Department, New York University School of Medicine, New York, USA

2 Virologisches Institut, Klinische und Molekulare Virologie, Universität Erlangen-Nürnberg, Erlangen, Germany

3 Institut für Virologie, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

4 Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA

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Retrovirology 2013, 10:26  doi:10.1186/1742-4690-10-26

Published: 5 March 2013

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.

Keywords:
HIV; SAMHD1; Macrophages; Vpx; Dendritic cells; Accessory proteins