Abstract
APOBEC3s (A3s) are single-stranded DNA cytosine deaminases that provide innate immune defences against retroviruses and mobile elements. A3s are specific to eutherian mammals because no direct homologs exist at the syntenic genomic locus in metatherian (marsupial) or prototherian (monotreme) mammals. However, the A3s in these species have the likely evolutionary precursors, the antibody gene deaminase AID and the RNA/DNA editing enzyme APOBEC1 (A1). Here, we used cell culture-based assays to determine whether opossum A1 restricts the infectivity of retroviruses including human immunodeficiency virus type 1 (HIV-1) and the mobility of LTR/non-LTR retrotransposons. Opossum A1 partially inhibited HIV-1, as well as simian immunodeficiency virus (SIV), murine leukemia virus (MLV), and the retrotransposon MusD. The mechanism of inhibition required catalytic activity, except for human LINE1 (L1) restriction, which was deamination-independent. These results indicate that opossum A1 functions as an innate barrier to infection by retroviruses such as HIV-1, and controls LTR/non-LTR retrotransposition in marsupials.
Highlights
Apolipoprotein B mRNA editing enzyme catalytic subunit 1 (APOBEC1, A1) is a cytidine deaminase that physiologically edits apoB mRNA, which encodes a key protein involved in lipid transport[1,2,3]
The A1 protein encoded in marsupials can edit a synthetic apoB mRNA substrate[23], its DNA-editing activity has not been determined
The expression of these proteins enhances the mutation of the bacterial RNA polymerase beta gene, which is reported as the frequency of rifampicin resistant (RifR) colonies
Summary
Apolipoprotein B (apoB) mRNA editing enzyme catalytic subunit 1 (APOBEC1, A1) is a cytidine deaminase that physiologically edits apoB mRNA, which encodes a key protein involved in lipid transport[1,2,3]. Eutherians encode at least one A3 family protein, there is no A3-like gene in the genomes of non-eutherian mammals (Fig. S1b), which was confirmed by the opossum genomic DNA sequence[21], a pan-species Z1 PCR analysis[22] and a BLAST search in this study (Fig. S1b) These observations suggest that the contribution of A1 to the innate immunity pathways of the marsupials could be greater than their contribution in eutherian mammals. The ability of this protein to edit apoB mRNA has previously been characterised[23], whether it inhibits retroviruses including HIV-1 and LTR/non-LTR mobile elements remains to be determined We addressed these questions using cell culture-based assays and found that opossum A1 from the small intestine is capable of restricting the infectivity of several retroviruses and the mobility of LTR/non-LTR retrotransposons. Our data indicate that the ability of A1 enzymes to protect the host genome from the invasion of foreign nucleic acids is conserved in marsupial and eutherian mammals
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