Blocking Type I Interferon Production: A New Therapeutic Option to Reduce the HIV-1-Induced Immune Activation

Figure 1

Proposed model of the type I interferon induction by HIV-1 and HIV-1-infected cells. Attachment to the CD4 receptor of plasmacytoid dendritic cells (PDC) triggers the HIV-1 uptake into an endosomal compartment. Subsequent acidification releases nucleic acids from lysed virions, preferentially recruits Toll-like receptor (TLR) 7, and activates the MyD88-dependent pathway. Translocation of the interferon response factor (IRF) 7 into the nucleus activates production of type I interferons (IFN). HIV-1 can also infect PDC via interaction with CD4 and the coreceptors. So far, it is unclear whether virions can escape from the endosomal compartment and initiate productive infection. Another pathway of type I interferon production was recently described in the absence of endosomal TLRs, namely, the recognition of HIV-1 RNA via cytosolic pattern recognition receptors (PRR) and IRF3 [39]. The role of this pathway for the IFN-alpha induction in PDC needs to be further elucidated.