%0 Journal Article
%T SAMHD1-Deficient CD14+ Cells from Individuals with Aicardi-Gouti¨¨res Syndrome Are Highly Susceptible to HIV-1 Infection
%A Andr¨¦ Berger
%A Andreas F. R. Sommer equal contributor
%A Jenny Zwarg equal contributor
%A Matthias Hamdorf
%A Karin Welzel
%A Nicole Esly
%A Sylvia Panitz
%A Andreas Reuter
%A Irene Ramos
%A Asavari Jatiani
%A Lubbertus C. F. Mulder
%A Ana Fernandez-Sesma
%A Frank Rutsch
%A Viviana Simon
%A Renate K£¿nig
%A Egbert Flory
%J PLOS Pathogens
%D 2011
%I Public Library of Science (PLoS)
%R 10.1371/journal.ppat.1002425
%X Myeloid blood cells are largely resistant to infection with human immunodeficiency virus type 1 (HIV-1). Recently, it was reported that Vpx from HIV-2/SIVsm facilitates infection of these cells by counteracting the host restriction factor SAMHD1. Here, we independently confirmed that Vpx interacts with SAMHD1 and targets it for ubiquitin-mediated degradation. We found that Vpx-mediated SAMHD1 degradation rendered primary monocytes highly susceptible to HIV-1 infection; Vpx with a T17A mutation, defective for SAMHD1 binding and degradation, did not show this activity. Several single nucleotide polymorphisms in the SAMHD1 gene have been associated with Aicardi-Gouti¨¨res syndrome (AGS), a very rare and severe autoimmune disease. Primary peripheral blood mononuclear cells (PBMC) from AGS patients homozygous for a nonsense mutation in SAMHD1 (R164X) lacked endogenous SAMHD1 expression and support HIV-1 replication in the absence of exogenous activation. Our results indicate that within PBMC from AGS patients, CD14+ cells were the subpopulation susceptible to HIV-1 infection, whereas cells from healthy donors did not support infection. The monocytic lineage of the infected SAMHD1 -/- cells, in conjunction with mostly undetectable levels of cytokines, chemokines and type I interferon measured prior to infection, indicate that aberrant cellular activation is not the cause for the observed phenotype. Taken together, we propose that SAMHD1 protects primary CD14+ monocytes from HIV-1 infection confirming SAMHD1 as a potent lentiviral restriction factor.
%U http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1002425