Opossum APOBEC1 is a DNA mutator with retrovirus and retroelement restriction activity

Terumasa Ikeda, Mayuko Shimoda, Diako Ebrahimi, John L. VandeBerg, Reuben S. Harris, Atsushi Koito, Kazuhiko Maeda

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish (US)
Article number46719
JournalScientific reports
Volume7
DOIs
StatePublished - 2017

Bibliographical note

Funding Information:
We thank Drs N. Gilbert, T. Heidmann, N.R. Landau, and E.T. Luning Prak for providing reagents. We also thank Ms. E. Kamada for secretarial assistance, Ms. K. Fukuda for technical assistance, and M. Araki, T. Ohsugi, and A. Sarai for valuable comments. This study was supported, in part, by JSPS KAKENHI (grant number 23590546 to A.K.; 26460580 to K.M), Global Centers of Excellence (COE) Program Global Education Research Center Aiming to Control AIDS, JSPS Research Fellowship for Young Scientists and Postdoctoral Fellowship (to T.I.), Okukubo Memorial Fund for Medical Research at Kumamoto University School of Medicine (to T.I.), SENSHIN Medical Research Foundation (to K.M.), NIH NIAID R37 AI064046 (to R.S.H.), and NIH NCI CA206309 (to R.S.H.). R.S.H. in an Investigator of the Howard Hughes Medical Institute.

Publisher Copyright:
© The Author(s) 2017.

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