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J Virol. 2015 Oct 21;90(1):474-85. doi: 10.1128/JVI.02612-15. Print 2016 Jan 1.

A Naturally Occurring Domestic Cat APOBEC3 Variant Confers Resistance to Feline Immunodeficiency Virus Infection.

Author information

1
Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Japan.
2
Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Japan Department of Microbiology, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan CREST, Japan Science and Technology Agency, Saitama, Japan.
3
Department of Bioinformatics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
4
Department of Biochemistry, Molecular Biology and Biophysics, Institute for Molecular Virology, Masonic Cancer Center, and Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota, USA.
5
Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
6
Department of Biochemistry, Molecular Biology and Biophysics, Institute for Molecular Virology, Masonic Cancer Center, and Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota, USA Howard Hughes Medical Institute, University of Minnesota, Minneapolis, Minnesota, USA.
7
Laboratory of Signal Transduction, Institute for Virus Research, Kyoto University, Kyoto, Japan Laboratory of Virolution, Institute for Virus Research, Kyoto University, Kyoto, Japan.
8
Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Japan CREST, Japan Science and Technology Agency, Saitama, Japan ksato@virus.kyoto-u.ac.jp.

Abstract

Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; A3) DNA cytosine deaminases can be incorporated into progeny virions and inhibit lentiviral replication. On the other hand, viral infectivity factor (Vif) of lentiviruses antagonizes A3-mediated antiviral activities by degrading A3 proteins. It is known that domestic cat (Felis catus) APOBEC3Z3 (A3Z3), the ortholog of human APOBEC3H, potently suppresses the infectivity of vif-defective feline immunodeficiency virus (FIV). Although a recent report has shown that domestic cat encodes 7 haplotypes (hap I to hap VII) of A3Z3, the relevance of A3Z3 polymorphism in domestic cats with FIV Vif has not yet been addressed. In this study, we demonstrated that these feline A3Z3 variants suppress vif-defective FIV infectivity. We also revealed that codon 65 of feline A3Z3 is a positively selected site and that A3Z3 hap V is subject to positive selection during evolution. It is particularly noteworthy that feline A3Z3 hap V is resistant to FIV Vif-mediated degradation and still inhibits vif-proficient viral infection. Moreover, the side chain size, but not the hydrophobicity, of the amino acid at position 65 determines the resistance to FIV Vif-mediated degradation. Furthermore, phylogenetic analyses have led to the inference that feline A3Z3 hap V emerged approximately 60,000 years ago. Taken together, these findings suggest that feline A3Z3 hap V may have been selected for escape from an ancestral FIV. This is the first evidence for an evolutionary "arms race" between the domestic cat and its cognate lentivirus.

IMPORTANCE:

Gene diversity and selective pressure are intriguing topics in the field of evolutionary biology. A direct interaction between a cellular protein and a viral protein can precipitate an evolutionary arms race between host and virus. One example is primate APOBEC3G, which potently restricts the replication of primate lentiviruses (e.g., human immunodeficiency virus type 1 [HIV-1] and simian immunodeficiency virus [SIV]) if its activity is not counteracted by the viral Vif protein. Here we investigate the ability of 7 naturally occurring variants of feline APOBEC3, APOBEC3Z3 (A3Z3), to inhibit FIV replication. Interestingly, one feline A3Z3 variant is dominant, restrictive, and naturally resistant to FIV Vif-mediated degradation. Phylogenetic analyses revealed that the ancestral change that generated this variant could have been caused by positive Darwinian selection, presumably due to an ancestral FIV infection. The experimental-phylogenetic investigation sheds light on the evolutionary history of the domestic cat, which was likely influenced by lentiviral infection.

PMID:
26491161
PMCID:
PMC4702554
DOI:
10.1128/JVI.02612-15
[Indexed for MEDLINE]
Free PMC Article

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