Paper Citing NAMD - Abstract
Vazquez, Nancy; Schmeisser, Hana; Dolan, Michael A.; Bekisz, Joseph; Zoon, Kathryn C.; Wahl, Sharon M.
Structural variants of IFN alpha preferentially promote antiviral functions
BLOOD, 118:2567-2577, SEP 1 2011
IFN alpha, a cytokine with multiple functions in innate and adaptive immunity and a potent inhibitor of HIV, exerts antiviral activity, in part, by enhancing apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3 (APOBEC3) family members. Although IFN alpha therapy is associated with reduced viral burden, this cytokine also mediates immune dysfunction and toxicities. Through detailed map-ping of IFN alpha receptor binding sites, we generated IFN alpha hybrids and mutants and determined that structural changes in the C-helix alter the ability of IFN to limit retroviral activity. Selective IFN alpha constructs differentially block HIV replication and their directional magnitude of inhibition correlates with APOBEC3 levels. Importantly, certain mutants exhibited reduced toxicity as reflected by induced indoleamine 2,3-dioxygenase (IDO), suggesting discreet and shared intracellular signaling pathways. Defining IFN structure and function relative to APOBEC and other antiviral genes may enable design of novel IFN-related molecules preserving beneficial antiviral roles while minimizing negative effects. (Blood. 2011;118(9):2567-2577)
