IL-27 Inhibits HIV-1 Replication in Dendritic Cells

IL-27 is a heterodimer belonging to the IL-12 family of cytokines (which also includes IL-12, IL-23, and IL-35), and is normally produced by activated macrophages and dendritic cells (DCs) (Imamichi et al., 2008; Frank et al., 2010). Most widely known for its anti-inflammatory properties, IL-27 also shows broad anti-viral effects. Studies in recent years have indicated IL-27 may hold promise as a means of protecting macrophages and CD4+ T-cells during HIV infection by inhibiting replication of the virus. In their recent publication in PLoS One, Dr. Tomozumi Imamichi from the Laboratory of Human Retrovirology at the Frederick National Laboratory for Cancer Research (Maryland, USA) and his team demonstrated IL-27 can similarly inhibit HIV replication in both immature and mature DCs. The team confirmed expression of IL-27 receptors (IL-27R) and HIV-1 receptors on monocyte-derived DCs, and then demonstrated IL-27 was able to inhibit HIV-1 replication in a dose-dependent manner. IL-12, IL-23, and IL-35 were not capable of reproducing this protective effect. Looking further into this mechanism, expression of type I interferons were shown to be unaltered and inhibition was deemed to be type I interferon-independent, interfering with replication at a point between viral entry and completion of reverse transcription. These encouraging results suggest that IL-27-based therapies could have broad application in targeting and treating all major cell types affected by HIV-1 in the future.

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