Introduction: Macrophages (Macs) are key target cells for HIV that supports the persistent by low level of replication compared to T cells. Consequently they act as a reservoir prior to antiviral therapy, particularly in brain, also in primary and secondary lymphoid tissue and in bone marrow. They also transfer infectious virus to T cells. HIV infection of Macs completely inhibits types III interferon production and I. However, it stimulates them to produce specific subsets of interferon-stimulated genes (ISGs) some of which have direct antiviral activity. This study investigates the mechanism of ISGs Induction in the absence of IFN.
Methods: The interferon regulatory factors IRF1 and IRF7, the transcriptional elongation factor Tat, the adaptor for RIGI (MAVS) and the adaptor for TLR7/8 (Myd88) were knockdown by specific siRNA 2 days prior to HIV infection to assess their effect on ISG induction at 6h and days 1-6 post infection by RT-PCR.
Results: Previously we have shown that ISG expression is governed by two phases: an initial induction through the detection of incoming HIV-1 genomic RNA at 6-48 h and then a second phase predominantly by posttranscriptional RNA as observed after 72 h. Now, we show that knockdown of either MAVS, Myd88, Tat, IRF1 or IRF7 have ablated the second phase of ISG subset.
Future directions: Currently we are examining the first phase of ISG induction.