Sulforaphane Reduces SAMHD1 Phosphorylation To Protect Macrophages from HIV-1 Infection
Hamayun J. Sharifi, Dakota N. Paine, Vincent A. Fazzari, Alexandria F. Tipple, Emilee Patterson, Carlos M. C. de Noronha
Abstract
Here, we show, for the first time, that the treatment of macrophages with Nrf2 mobilizers, known activators of antioxidant responses, increases the fraction of SAMHD1 without a regulatory phosphate at position 592. We demonstrate that this decreases infection of macrophages by HIV-1. Phosphorylated SAMHD1 is important for DNA repair, the suppression of LINE elements, the maintenance of HIV-1 in a latent state, and the prevention of excessive type I interferon responses, while unphosphorylated SAMHD1 blocks HIV infection. SAMHD1 impacts many viruses and is involved in various cancers, so knowledge of how it works and how it is regulated has broad implications for the development of therapeutics. Redox-modulating therapeutics are already in clinical use or under investigation for the treatment of many conditions. Thus, understanding the impact of redox modifiers on controlling SAMHD1 phosphorylation is important for many areas of research in microbiology and beyond.