期刊
JOURNAL OF IMMUNOLOGY
卷 190, 期 7, 页码 3346-3353出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1201184
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资金
- European Commission [EC-FP7-242135 CHAARM, EC-FP6-037611 EUROPRISE]
- Hedlunds Foundation
- Swedish Foundation for Strategic Research
- SLL-ALF
Cytokines and IFNs, such as TNF-alpha and IFN-alpha, upregulate costimulatory molecules in monocyte-derived dendritic cells ( MDDCs), enabling effective Ag presentation to T cells. This activation of MDDCs is often accompanied by upregulation of apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3 ( APOBEC3) ( A3) family proteins that are able to restrict HIV-1 replication in MDDCs by inducing hypermutations in the viral genome. In this study, we show that TNF-alpha upregulates costimulatory molecules and are able to restrict HIV-1(BaL) replication in MDDCs without significant induction of A3G, A3A, or A3F. Conversely, low quantities of IFN-alpha failed to upregulate costimulatory molecules, did not induce IL-12p40 or migration, but significantly induced A3G, A3A, and A3F mRNA expression and restricted viral replication in MDDCs. We also showed that transmission of HIV-1 from MDDCs to autologous T cells was significantly reduced in the presence of IFN-alpha. Sequence analyses detected the induction of high frequency of G-to-A hypermutations in the env genes from HIV-1(BaL)-infected MDDCs treated with low quantities of IFN-alpha 2b. These findings show that low quantities of IFN-alpha can induce functional A3 family proteins and restrict HIV-1 replication in MDDCs while keeping an immature nonmigratory phenotype, supporting further investigations of modalities that enhance retroviral restriction factors. In addition, the findings highlight the role of IFN-alpha as a double-edged sword in HIV-1 infection, and we show that IFN-alpha can be powerful in reducing HIV-1 infection both in MDDCs and T cells. The Journal of Immunology, 2013, 190: 3346-3353.
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