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| Content Provider | PubMed Central |
|---|---|
| Author | Diana, Ayinde Bruel, Timothée Sylvain, Cardinaud Porrot, Françoise Prado, Julia G. Moris, Arnaud Schwartz, Olivier |
| Editor | Silvestri, G. |
| Copyright Year | 2015 |
| Abstract | Monocyte-derived dendritic cells (MDDC) stimulate CD8+ cytotoxic T lymphocytes (CTL) by presenting endogenous and exogenous viral peptides via major histocompatibility complex class I (MHC-I) molecules. MDDC are poorly susceptible to HIV-1, in part due to the presence of SAMHD1, a cellular enzyme that depletes intracellular deoxynucleoside triphosphates (dNTPs) and degrades viral RNA. Vpx, an HIV-2/SIVsm protein absent from HIV-1, antagonizes SAMHD1 by inducing its degradation. The impact of SAMHD1 on the adaptive cellular immune response remains poorly characterized. Here, we asked whether SAMHD1 modulates MHC-I-restricted HIV-1 antigen presentation. Untreated MDDC or MDDC pretreated with Vpx were exposed to HIV-1, and antigen presentation was examined by monitoring the activation of an HIV-1 Gag-specific CTL clone. SAMHD1 depletion strongly enhanced productive infection of MDDC as well as endogenous HIV-1 antigen presentation. Time-lapse microscopy analysis demonstrated that in the absence of SAMHD1, the CTL rapidly killed infected MDDC. We also report that various transmitted/founder (T/F) HIV-1 strains poorly infected MDDC and, as a consequence, did not stimulate CTL. Vesicular stomatitis virus glycoprotein (VSV-G) pseudotyping of T/F alleviated a block in viral entry and induced antigen presentation only in the absence of SAMHD1. Furthermore, by using another CTL clone that mostly recognizes incoming HIV-1 antigens, we demonstrate that SAMHD1 does not influence exogenous viral antigen presentation. Altogether, our results demonstrate that the antiviral activity of SAMHD1 impacts antigen presentation by DC, highlighting the link that exists between restriction factors and adaptive immune responses. |
| Related Links | http://dx.doi.org/10.1128/jvi.00069-15 |
| Ending Page | 7006 |
| Page Count | 13 |
| Starting Page | 6994 |
| File Format | |
| ISSN | 0022538X |
| e-ISSN | 10985514 |
| Journal | Journal of Virology |
| Issue Number | 14 |
| Volume Number | 89 |
| Language | English |
| Publisher | American Society for Microbiology |
| Publisher Date | 2015-07-15 |
| Access Restriction | Open |
| Rights Holder | American Society for Microbiology |
| Subject Keyword | Immunology Virology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Virology Immunology Microbiology Insect Science |
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