title: Restriction of diverse retroviruses by SAMHD1.
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.
  
  
  CONCLUSIONS
  The results suggest that SAMHD1 has broad anti-retroviral activity against which most viruses have not found an escape.
authors.affiliation: Microbiology Department, New York University School of Medicine, New York, USA. thomas.gramberg@viro.med.uni-erlangen.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Gramberg
authors.forename: Tanja
authors.initials: T
authors.lastname: Kahle
authors.forename: Nicolin
authors.initials: N
authors.lastname: Bloch
authors.forename: Sabine
authors.initials: S
authors.lastname: Wittmann
authors.forename: Erik
authors.initials: E
authors.lastname: Müllers
authors.forename: Waaqo
authors.initials: W
authors.lastname: Daddacha
authors.forename: Henning
authors.initials: H
authors.lastname: Hofmann
authors.forename: Baek
authors.initials: B
authors.lastname: Kim
authors.forename: Dirk
authors.initials: D
authors.lastname: Lindemann
authors.forename: Nathaniel R
authors.initials: NR
authors.lastname: Landau
mesh_terms: D002460:Cell Line; D003713:Dendritic Cells / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D008264:Macrophages / Q000276:immunology / Q000821:virology*; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism / Q000494:pharmacology*; D022423:Myeloid Cells / Q000378:metabolism / Q000821:virology*; D012190:Retroviridae / Q000145:classification / Q000187:drug effects* / Q000472:pathogenicity* / Q000502:physiology; D000076106:SAM Domain and HD Domain-Containing Protein 1; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins