Restriction by APOBEC3 proteins of endogenous retroviruses with an extracellular life cycle: ex vivo effects and in vivo"traces" on the murine IAPE and human HERV-K elements

Abstract

Background: APOBEC3 cytosine deaminases have been demonstrated to restrict infectivity of a series of retroviruses, with different efficiencies depending on the retrovirus. In addition, APOBEC3 proteins can severely restrict the intracellular transposition of a series of retroelements with a strictly intracellular life cycle, including the murine IAP and MusD LTR-retrotransposons.

Large-scale DNA editing of retrotransposons accelerates mammalian genome evolution

“…Investigation of the sequences surrounding the edited nucleotides revealed dominance of adenosines at position + 2 relative to the editing site (GxA→AxA motif; the underlined G is the editing site; Methods and Supplementary Table S1). This is in agreement with previous experimental studies [14][15][16][17][18][19][20]23,24 and supports the identification of these mismatches as an outcome of mouse APOBEC3 activity.…”

“…This process is thus called DNA editing. In recent years, it was shown that active LTR (long terminal repeat) retrotransposons, which are endogenous retroviruses, can also be edited [14][15][16][17][18][19][20][21] . However, the impact of DNA editing on genome variability has not been explored to date 22 .…”

Transposable elements in the mammalian germline: a comfortable niche or a deadly trap?

“…APO-BEC3G notably reduces the replication of human immunodeficiency virus, by inducing the accumulation of uracil mutations on the nascent retroviral complementary DNA strand and subsequently inactivating the newly integrated copy (Bishop et al, 2004). Retrotransposition assays have shown that APOBEC3A, 3B, 3C and 3F enzymes are potent restrictors of different classes of LTR-and non-LTR retrotransposons, such as L1, IAP, Alu, human ERV-K and MusD elements in human and mouse cells (Bogerd et al, 2006;Esnault et al, 2006Esnault et al, , 2008. AID, another cytosine deaminase with a wider phylogenetic distribution, also represses L1 and MusD retrotransposition in mouse cells (MacDuff et al, 2009).…”

The MOV10 Helicase Inhibits LINE-1 Mobility

“…The same amounts of RNA samples were subject to electrophoresis in 1% denaturing agarose gels. After being transferred onto nylon membranes, RNA was hybridized to 32 P-labeled DNA probes that were amplified using primers 5Ј-CGGATCAAGCGTAT-GCAGCC-3Ј/5Ј-GCAGGTTCTCCGGCCGCTTG-3Ј and recognized the neomycin resistance gene sequence. The same probes bind to the RNA of CMV-L1-neo RT , IAP-neo TNF , and MusD-neo TNF .…”

“…To control massively activated LINE-1, germ line cells express a special type of small RNA named piRNA (piwi-interacting RNA) that arms Piwi (P-element induced wimpy testis) proteins to suppress LINE-1 (25,26). Furthermore, it has been reported that APOBEC3 (apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3) proteins, which inhibit the infection of a broad range of viruses particularly retroviruses (27)(28)(29)(30)(31), also provide another mechanism to control LINE-1 (32)(33)(34). It appears that cells manage to use the same mechanism to protect themselves from either extracellular or intracellular insults that share common biochemical features.…”