Abstract
SAMHD1 restricts human immunodeficiency virus type 1 (HIV-1) infection in a cell-type specific manner. Other than primary
monocyte derived cells and resting CD4+ T cells, the SAMHD1-mediated HIV-1 block was reported only in phorbol
12-myristate 13-acetate (PMA)-differentiated THP-1 and U937 monocyte cell lines. We previously reported that SAMHD1
restricted HIV-1 infection in TE671 rhabdomyosarcoma cells in addition to these cell lines. In this study, we compared the
amounts of the full-length SAMHD1 and its deletion mutants, SAM domain containing N-terminal fragment (residues 1-119,
SAMHD1n) and HD domain containing C-terminal fragment (120-626, SAMHD1c) in U937, TE671, and HeLa cells. The results
showed that the full-length SAMHD1 and SAMHD1n proteins were significantly more abundant than the SAMHD1c protein
in TE671 and differentiated U937 cells. The proteasome inhibitor MG132 increased the amount of the SAMHD1c and the
SAMHD1c-fused GFP proteins. In contrast, the fusion of the SAMHD1n to the APOBEC3G protein inhibited Vif-induced proteasomal
degradation in TE671 and in differentiated U937 cells. These results indicated that the SAMHD1 C-terminal HD
domain-containing region leads the SAMHD1 to proteasomal degradation, and the SAMHD1 N-terminal SAM domain-containing
region stabilizes the protein. Our study showed that the SAMHD1 protein expression is post-translationally regulated
and the significance of SAM and HD domains for the full-length SAMHD1 protein stability. Further, we suggest that the SAM
domain-containing N-terminal region participate in the cell-type specific restrictive function of SAMHD1 against HIV-1 infection,
by protein stabilization.
