HIV infection in humanized mice: role of type I interferon on disease progression (VIR9P.1139)

Abstract

Abstract HIV and SIV disease progression is associated with chronic expression of type I IFN and IFN-stimulated genes. A recent study showed that a high-dose injection of IFN-1 early during primary SIV infection in the rhesus macaque model was protective, while neutralization of endogenous IFN-1 was deleterious. In contrast, in the same animal model, prolonged IFN-1 administration accelerated disease development in the chronic stage of the infection. To better understand the role of IFN-1 during HIV infection, we used humanized-PBL mouse model for this study. The advantage of this model is that there is no endogenous interferon production upon HIV infection, allowing analysis of IFN-1 therapy. Since continuous presence of IFN-1 is detrimental in the SIV model, we hypothesized that intermittent treatment with IFN-1 may be protective against HIV infection. To test this hypothesis, we carried out intermittent pegasys (peg-interferon alpha) treatment after HIV infection in human PBL infused NOD-scid IL2rγcnull (hu-PBL) mice. This treatment with pegasys diminished HIV replication and delayed CD4 depletion compared to control mice. To further test the role of IFN, we are currently using humanized BLT mouse model of HIV infection. HIV infection in BLT mice leads to continuous production of high levels of type-I IFNs; and thus, we are studying the effects of continuous or intermittent IFN blockade using type I IFN antagonist. The results will be discussed.