SAMHD1-deficient CD14+ cells from individuals with Aicardi-Goutières syndrome are highly susceptible to HIV-1 infection

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-goutières 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. © 2011 berger et al.