Retroelements versus APOBEC3 family members: No great escape from the magnificent seven

Abstract

Retroelements comprise a large and successful family of transposable genetic elements that, through intensive infiltration, have shaped the genomes of humans and other mammals over millions of years. In fact, retrotransposons now account for approximately 45% of the human genome. Because of their genomic mobility called retrotransposition, some retroelements can cause genetic diseases; such retrotransposition events occur not only in germ cells but also in somatic cells, posing a threat to genomic stability throughout all cellular populations. In response, mammals have developed intrinsic immunity mechanisms that provide resistance against the deleterious effects of retrotransposition. Among these, seven members of the APOBEC3 (A3) family of cytidine deaminases serve as highly active, intrinsic, antiretroviral host factors. Certain A3 proteins effectively counteract infections of retroviruses such as HIV-1, as well as those of other virus families, while also blocking the transposition of retroelements. Based on their preferential expression in the germ cells, in which retrotransposons may be active, it is likely that A3 proteins were acquired through mammalian evolution primarily to inhibit retrotransposition and thereby maintain genomic stability in these cells. This review summarizes the recent advances in our understanding of the interplay between the retroelements currently active in the human genome and the anti-retroelement A3 proteins.

Retrotransposons as regulators of gene expression

“…Indeed, mice lacking the critical autophagy gene, Atg6/Beclin1, are characterized by higher levels of retrotransposon RNAs and increased rates of genomic insertions (98). Additionally, retrotransposition is restricted in both somatic and germ cells by members of the apolipoprotein B mRNA-editing enzyme 3 (APOBEC3) family (89, 99). …”

Human APOBEC3 Induced Mutation of Human Immunodeficiency Virus Type-1 Contributes to Adaptation and Evolution in Natural Infection

“…APOBEC3D, APOBEC3F, APOBEC3G and APOBEC3H are the cellular targets for the HIV-1 accessory protein Vif [14], [15], which can counteract the protective role of this innate immune defense mechanism. The HIV-1 protein Vif induces polyubiquitylation through simultaneously binding to APOBEC3 proteins and the cullin5-elongin B/C-Rbx2 ubiquitin ligase complex.…”

Mammalian Endogenous Retroviruses

“…Given their potential for harm, genomes have evolved multiple lines of defense against ERVs involving both epigenetic modifications that curtail ERV transcription as well as host protein restriction factors that target other phases of the ERV replication cycle (54,66,67,68,69,70).…”