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 w...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-12-01
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| Series: | PLoS Pathogens |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22174685/?tool=EBI |
| _version_ | 1818735404410470400 |
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| author | André Berger Andreas F R Sommer Jenny Zwarg Matthias Hamdorf Karin Welzel Nicole Esly Sylvia Panitz Andreas Reuter Irene Ramos Asavari Jatiani Lubbertus C F Mulder Ana Fernandez-Sesma Frank Rutsch Viviana Simon Renate König Egbert Flory |
| author_facet | André Berger Andreas F R Sommer Jenny Zwarg Matthias Hamdorf Karin Welzel Nicole Esly Sylvia Panitz Andreas Reuter Irene Ramos Asavari Jatiani Lubbertus C F Mulder Ana Fernandez-Sesma Frank Rutsch Viviana Simon Renate König Egbert Flory |
| author_sort | André Berger |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-18T00:20:43Z |
| format | Article |
| id | doaj.art-a25138a23dde4fd5b01d7754d13c5a24 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-18T00:20:43Z |
| publishDate | 2011-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-a25138a23dde4fd5b01d7754d13c5a242022-12-21T21:27:21ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742011-12-01712e100242510.1371/journal.ppat.1002425SAMHD1-deficient CD14+ cells from individuals with Aicardi-Goutières syndrome are highly susceptible to HIV-1 infection.André BergerAndreas F R SommerJenny ZwargMatthias HamdorfKarin WelzelNicole EslySylvia PanitzAndreas ReuterIrene RamosAsavari JatianiLubbertus C F MulderAna Fernandez-SesmaFrank RutschViviana SimonRenate KönigEgbert FloryMyeloid 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22174685/?tool=EBI |
| spellingShingle | André Berger Andreas F R Sommer Jenny Zwarg Matthias Hamdorf Karin Welzel Nicole Esly Sylvia Panitz Andreas Reuter Irene Ramos Asavari Jatiani Lubbertus C F Mulder Ana Fernandez-Sesma Frank Rutsch Viviana Simon Renate König Egbert Flory SAMHD1-deficient CD14+ cells from individuals with Aicardi-Goutières syndrome are highly susceptible to HIV-1 infection. PLoS Pathogens |
| title | SAMHD1-deficient CD14+ cells from individuals with Aicardi-Goutières syndrome are highly susceptible to HIV-1 infection. |
| title_full | SAMHD1-deficient CD14+ cells from individuals with Aicardi-Goutières syndrome are highly susceptible to HIV-1 infection. |
| title_fullStr | SAMHD1-deficient CD14+ cells from individuals with Aicardi-Goutières syndrome are highly susceptible to HIV-1 infection. |
| title_full_unstemmed | SAMHD1-deficient CD14+ cells from individuals with Aicardi-Goutières syndrome are highly susceptible to HIV-1 infection. |
| title_short | SAMHD1-deficient CD14+ cells from individuals with Aicardi-Goutières syndrome are highly susceptible to HIV-1 infection. |
| title_sort | samhd1 deficient cd14 cells from individuals with aicardi goutieres syndrome are highly susceptible to hiv 1 infection |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22174685/?tool=EBI |
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