SAMHD1 restricts HIV-1 infection in resting CD4+ T cells
| Autor: | Sarah Schmidt, Guido H. Wabnitz, Ina Ambiel, Elina Erikson, Kristina Schenkova, Baek Kim, Renate König, Felix Lasitschka, Manja Burggraf, Waaqo Daddacha, Oliver T. Keppler, Xiaoyu Pan, Nathaniel R. Landau, Frank Rutsch, Egbert Flory, Hanna Mari Baldauf, Serkan Sertel, Sylvia Panitz, Thomas Gramberg, Oliver T. Fackler |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
CD4-Positive T-Lymphocytes
T cell Human Immunodeficiency Virus Proteins HIV Infections Biology Nervous System Malformations Virus Replication Article General Biochemistry Genetics and Molecular Biology SAM Domain and HD Domain-Containing Protein 1 Interleukin 21 Autoimmune Diseases of the Nervous System Immune system medicine Humans Cytotoxic T cell Viral Regulatory and Accessory Proteins Monomeric GTP-Binding Proteins Virion virus diseases Reverse Transcription General Medicine Virology Reverse transcriptase Lymphatic system medicine.anatomical_structure Viral replication HIV-2 HIV-1 SAMHD1 |
| Zdroj: | Nature Medicine. 18:1682-1688 |
| ISSN: | 1546-170X 1078-8956 |
| Popis: | Unlike activated CD4(+) T cells, resting CD4(+) T cells are highly resistant to productive HIV-1 infection. Early after HIV-1 entry, a major block limits reverse transcription of incoming viral genomes. Here we show that the deoxynucleoside triphosphate triphosphohydrolase SAMHD1 prevents reverse transcription of HIV-1 RNA in resting CD4(+) T cells. SAMHD1 is abundantly expressed in resting CD4(+) T cells circulating in peripheral blood and residing in lymphoid organs. The early restriction to infection in unstimulated CD4(+) T cells is overcome by HIV-1 or HIV-2 virions into which viral Vpx is artificially or naturally packaged, respectively, or by addition of exogenous deoxynucleosides. Vpx-mediated proteasomal degradation of SAMHD1 and elevation of intracellular deoxynucleotide pools precede successful infection by Vpx-carrying HIV. Resting CD4(+) T cells from healthy donors following SAMHD1 silencing or from a patient with Aicardi-Goutières syndrome homozygous for a nonsense mutation in SAMHD1 were permissive for HIV-1 infection. Thus, SAMHD1 imposes an effective restriction to HIV-1 infection in the large pool of noncycling CD4(+) T cells in vivo. Bypassing SAMHD1 was insufficient for the release of viral progeny, implicating other barriers at later stages of HIV replication. Together, these findings may unveil new ways to interfere with the immune evasion and T cell immunopathology of pandemic HIV-1. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|