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- Title
SAMHD1-Deficient CD14+ Cells from Individuals with Aicardi-Goutières Syndrome Are Highly Susceptible to HIV-1 Infection.
- Authors
Berger, André; Sommer, Andreas F. R.; Zwarg, Jenny; Hamdorf, Matthias; Welzel, Karin; Esly, Nicole; Panitz, Sylvia; Reuter, Andreas; Ramos, Irene; Jatiani, Asavari; Mulder, Lubbertus C. F.; Sesma, Ana Fernandez-; Rutsch, Frank; Simon, Viviana; König, Renate; Flory, Egbert
- Abstract
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.
- Subjects
HIV; UBIQUITIN; HIV infections; CYTOKINES; SINGLE nucleotide polymorphisms
- Publication
PLoS Pathogens, 2011, Vol 7, Issue 12, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1002425