A naturally occurring feline APOBEC3 variant that loses anti-lentiviral activity by lacking two amino acid residues

Yoriyuki Konno; Shumpei Nagaoka; Izumi Kimura; Mahoko Takahashi Ueda; Ryuichi Kumata; Jumpei Ito; So Nakagawa; Tomoko Kobayashi; Yoshio Koyanagi; Kei Sato

doi:10.1099/jgv.0.001046

A naturally occurring feline APOBEC3 variant that loses anti-lentiviral activity by lacking two amino acid residues

J Gen Virol. 2018 May;99(5):704-709. doi: 10.1099/jgv.0.001046.

Authors

Yoriyuki Konno^{1

2}, Shumpei Nagaoka^{1

2}, Izumi Kimura^{1

3}, Mahoko Takahashi Ueda⁴, Ryuichi Kumata^{1

5}, Jumpei Ito⁶, So Nakagawa^{4

7}, Tomoko Kobayashi⁸, Yoshio Koyanagi¹, Kei Sato^{9

1

10}

Affiliations

¹ Laboratory of Systems Virology, Department of Biosystems Science, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
² Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
³ Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
⁴ Micro/Nano Technology Center, Tokai University, Kanagawa, Japan.
⁵ Faculty of Science, Kyoto University, Kyoto, Japan.
⁶ Division of Human Genetics, Department of Integrated Genetics, National Institute of Genetics, Shizuoka, Japan.
⁷ Department of Molecular Life Science, Tokai University School of Medicine, Tokai University, Kanagawa, Japan.
⁸ Department of Animal Science, Faculty of Agriculture, Tokyo University of Agriculture, Kanagawa, Japan.
⁹ CREST, Japan Science and Technology Agency, Saitama, Japan.
¹⁰ Present address: Division of Systems Virology, Department of Infectious Disease Control, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, 1088639 Tokyo, Japan.

PMID: 29611801
DOI: 10.1099/jgv.0.001046

Abstract

Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) is a mammalian protein that restricts lentiviral replication. Various polymorphisms of mammalian APOBEC3 genes have been observed in humans, Old World monkeys and domestic cats; however, the genetic diversity of APOBEC3 genes in other mammals remains unaddressed. Here we identify a novel haplotype of the feline APOBEC3Z3 gene, an APOBEC3 gene that restricts feline immunodeficiency virus (FIV) replication, in a Eurasian lynx (Lynx lynx). Compared to the previously identified lynx APOBEC3Z3 (haplotype I), the new sequence (haplotype II) harbours two amino acid deletions (Q16 and H17) and a nonsynonymous substitution (R68Q). Interestingly, lynx APOBEC3Z3 haplotype II does not suppress FIV infectivity, whereas haplotype I does. Mutagenesis experiments further revealed that deleting two amino acids (Q16 and H17) causes anti-FIV activity loss. This report demonstrates that a naturally occurring APOBEC3 variant loses anti-lentiviral activity through the deletion of two amino acid residues.

Keywords: APOBEC3; FIV; evolutionary arms race; felids; lentivirus; lynx.