Type I interferon: understanding its role in HIV pathogenesis and therapy

Despite 30 years of intense research, the basis by which HIV causes immunodeficiency is still poorly understood. The interferon system (IFN) has been implicated in disease pathogenesis since the 1980’s. In early work, we observed widespread induction of antiviral genes in cynomolgus macaques undergoing pathogenic SIV infection, specifically Interferon Stimulated Genes (ISGs). However, despite the impressive breadth of this response, there was no apparent effect on viral load. We next made the observation that African monkey species that do not develop AIDS after SIV infection are able to rapidly down-regulate their IFN system, whereas humans and AIDS-susceptible monkey species maintain high activation of the IFN system indefinitely. The decreased IFN state observed in non-human primates was also observed in HIV-infected  “Viremic Non-Progressors” – patients that remain asymptomatic despite long-term high viral load.  Collectively, these studies demonstrate that uncontrolled, persistent IFN production in chronic HIV infection is harmful. A central focus of Dr. Bosinger's research is to develop therapies targeting the IFN response and test them in the SIV/NHP model.

Type I interferon- understanding its role in HIV pathogenesis and therapy framed.png

Plasmacytoid dendritic cells (pDCs) are immune cells that secrete large amounts of type 1 IFN in response to viral infection. In acute HIV infections, type I IFNs are critical in activating NK cells and upregulating restriction factors to target the virus. However, in chronic infections, the product of pDCs can lead to CD4 T cell loss and immune exhaustion. Future studies in our lab will investigate the effect of pDC depletion on disease progression in rhesus macaques in the hope of avoiding immune exhaustion.