HIV blocks Type I Interferon signaling through disruption of STAT1 phosphorylation.

Abstract

Abstract Although a considerable amount of research has been undertaken to find new strategies to treat acquired immunodeficiency syndrome (AIDS), which is caused by human immunodeficiency virus (HIV), it still remains a global health complication. Type 1 Interferon (IFN) is well-known to activate the antiviral state via the JAK/STAT pathway. However, HIV is able to bypasses multiple antiviral responses due to encoded proteins that disrupt various steps in the stimulation of the IFN-induced antiviral state. We hypothesize that HIV proteins block the antiviral state by disrupting the JAK/STAT signaling pathway even in the presence of exogenous IFN-α. We found that HIV proteins inhibit the phosphorylation of STAT1 in CD4+T cells. Furthermore, we found a reduction of phosphorylated STAT1 after IFN-α stimulation in cells expressing Vpu and Nef. On the other hand, the expression levels of Tyk2 and total STAT1 are not affected by Vpu or Nef. We also observed a reduction in the antiviral effect induced by IFN-α using infection of VSV-GFP in a Vpu stable cell line. In conclusion, HIV IFN-α signaling via expression of Vpu and Nef allowing for reduction in antiviral state establishment by IFN-α. In the future, we plan to assess Vpu and Nef inhibition of the IFN-α mediated antiviral state in macrophages to see if it is similar to the effect in T cells.