CLASS I IFNs

(IFN-α and IFN-β). In peripheral blood mononuclear cells (PBMC) IFN-α is mainly produced by monocytes and plasmacytoid dendritic cells (PDC). IFN-α influences antibody (Ab) production, cell cytotoxicity by T and NK cells, activity of T suppressor/regulatory cells, and anti-tumor activity [13].

Indded, IFN-α has shown the capacity to inhibit both reverse transcription and viral expression from integrated provirus in acutely infected primary cells [15], HIV replication in primary monocyte-derived macrophages (MDM) [16] and virion release from chronically infected cell lines [17]. Indeed, in the last year another anti-HIV mechanism attributed to IFN-α has been shown in many primary cells, such as human macrophages [18], PDC [19], resting but not activated CD4+ T cells [20] and brain microvascular endothelial cells [21]. This mechanism relies on the ability of IFN-α to induce oversexpression of active form of apolipoprotein B m-RNA-editing enzyme-catalytic polypeptide-like (APOBEC) family members, such as APOBEC-3G and 3F, 3A and 3C, thus preventing the reverse transcription of incoming virus [22].

HIV infection has been reported to influence IFN-α expression dependending on the cell type. In fact, in HIV+ individuals DC are chracterized by decresed levels of IFN-αexpression [23], whereas expression by PDC is inversely correlated with viral load [24]. Indeed, HIV+ individuals on highly active anti-retroviral therapy (HAART) were characterized by decreased plasma viremia, and increased number of IFN-αproducing PDC [25]. However, other reports did not show influence of viral load and HAART on the capacity of PDC to produce IFN-α [26]. In another anatomical compartment, such as the cerebrospinal fluid, levels of IFN-α have been positively associated with viral load and the staging of AIDS dementia complex [27].