Characterization of molecular attributes that influence LINE-1 restriction by all seven human APOBEC3 proteins

Abstract

LINE-1 (L1) is a non-long terminal repeat (LTR) retrotransposon inserted throughout the human genome. APOBEC3 (A3) proteins are part of a network of host intrinsic defenses capable of restricting retroviruses and the replication of L1 retroelements. These enzymes inactivate retroviruses primarily through deamination of single-stranded viral DNA. In contrast, only A3A deaminates L1 DNA, while the other six A3 proteins restrict L1 to varying degrees through yet poorly defined mechanisms. Here we provide further insight into the molecular attributes of L1 restriction by A3 proteins. We specifically investigated the roles of A3 protein oligomerization, interactions with RNA and their binding to the various L1 proteins. Our results show that compromising the ability of A3 proteins to oligomerize or interact with a nucleic acid substrate diminished L1 restriction to varying degrees. However the efficiency of their binding to L1 proteins did not predict restriction or the potency of the restriction.

Keywords: APOBEC3; Intrinsic immunity; LINE-1; ORF0p; ORF1p; ORF2p; Retroelements; Retroviral restriction factors.