Autor: |
Qian Chen, Sanjay Swaminathan, De Yang, Lue Dai, Hongyan Sui, Jun Yang, Ronald L Hornung, Yanmei Wang, Da Wei Huang, Xiaojun Hu, Richard A Lempicki, Tomozumi Imamichi |
Jazyk: |
angličtina |
Rok vydání: |
2013 |
Předmět: |
|
Zdroj: |
PLoS ONE, Vol 8, Iss 3, p e59194 (2013) |
Druh dokumentu: |
article |
ISSN: |
1932-6203 |
DOI: |
10.1371/journal.pone.0059194 |
Popis: |
IL-27, a member of the IL-12 family of cytokines, plays an important and diverse role in the function of the immune system. Whilst generally recognized as an anti-inflammatory cytokine, in addition IL-27 has been found to have broad anti-viral effects. Recently, IL-27 has been shown to be a potent inhibitor of HIV-1 infection in CD4+ T cells and macrophages. The main objective of this study was to see whether IL-27 has a similar inhibitory effect on HIV-1 replication in dendritic cells (DCs). Monocytes were differentiated into immature DCs (iDCs) and mature DCs (mDCs) with standard techniques using a combination of GM-CSF, IL-4 and LPS. Following differentiation, iDCs were infected with HIV-1 and co-cultured in the presence or absence of IL-27. IL-27 treated DCs were shown to be highly potent inhibitors of cis HIV-1, particularly of CCR5 tropic strains. Of note, other IL-12 family members (IL-12, IL-23 and IL-35) had no effect on HIV-1 replication. Microarray studies of IL-27 treated DCs showed no up-regulation of Type I (IFN) gene expression. Neutralization of the Type-I IFN receptor had no impact on the HIV inhibition. Lastly, IL-27 mediated inhibition was shown to act post-viral entry and prior to completion of reverse transcription. These results show for the first time that IL-27 is a potent inhibitor of cis HIV-1 infection in DCs by a Type I IFN independent mechanism. IL-27 has previously been reported to inhibit HIV-1 replication in CD4+ T cells and macrophages, thus taken together, this cytokine is a potent anti-HIV agent against all major cell types targeted by the HIV-1 virus and may have a therapeutic role in the future. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
|