Figure from O'Connell and Siliciano (2).
This study has provided an interesting new insight into the immune mechanisms contributing to the progression of AIDS. Specifically, it appears that IRF7 polymorphisms resulting in the attenuation of the type I IFN response in sooty mangabeys protects against the development of AIDS. These mutations have been preserved in sooty mangabeys as they offer an evolutionary advantage, namely a reduced susceptibility to immunodeficiency disease. This implies that the pathogenesis of AIDS in susceptible species may be a combination of both viral replication and prolonged immune activation. Based on this research, a potential therapeutic strategy to combat AIDS would involve inhibiting virus binding to CD4 on pDCs, thus attenuating cell proliferation. In addition, the inhibition of excessive type I IFN release by pDCs may prove to be beneficial, either through the use neutralising IFNa antibodies or by specifically targeting IRF7. However, these potential strategies are not without limitations, as an inhibition of type I IFN production would leave a patient dangerously immunocompromised. Instead, more research into the contribution of innate immune mechanisms to AIDS progression may result in the use of specific inhibitors as part of a combinatorial therapeutic approach.
(1) Mandl et al. Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections. Nat Med. 2008 Oct;14(10):1077-87.
(2) O'Connell and Siliciano. Immune alteration fends off AIDS. Nat Med. 2008 Oct;14(10):1016-8.