Defining APOBEC3 Expression Patterns in Human Tissues and Hematopoietic Cell Subsets

Abstract

ABSTRACTHuman APOBEC3 enzymes are cellular DNA cytidine deaminases that inhibit and/or mutate a variety of retroviruses, retrotransposons, and DNA viruses. Here, we report a detailed examination of humanAPOBEC3gene expression, focusing on APOBEC3G (A3G) and APOBEC3F (A3F), which are potent inhibitors of human immunodeficiency virus type 1 (HIV-1) infection but are suppressed by HIV-1 Vif. A3G and A3F are expressed widely in hematopoietic cell populations, including T cells, B cells, and myeloid cells, as well as in tissues where mRNA levels broadly correlate with the lymphoid cell content (gonadal tissues are exceptions). By measuring mRNA copy numbers, we find thatA3GmRNA is ∼10-fold more abundant thanA3FmRNA, implying that A3G is the more significant anti-HIV-1 factor in vivo.A3GandA3Flevels also vary between donors, and these differences are sustained over 12 months. Responses to T-cell activation or cytokines reveal thatA3GandA3FmRNA levels are induced ∼10-fold in macrophages and dendritic cells (DCs) by alpha interferon (IFN-α) and ∼4-fold in naïve CD4+T cells. However, immunoblotting revealed that A3G protein levels are induced by IFN-α in macrophages and DCs but not in T cells. In contrast, T-cell activation and IFN-γ had a minimal impact onA3GorA3Fexpression. Finally, we noted thatA3AmRNA expression and protein expression are exquisitely sensitive to IFN-α induction in CD4+T cells, macrophages, and DCs but not to T-cell activation or other cytokines. Given that A3A does not affect HIV-1 infection, these observations imply that this protein may participate in early antiviral innate immune responses.