TY - JOUR
T1 - A naturally occurring domestic cat APOBEC3 variant confers resistance to feline immunodeficiency virus infection
AU - Yoshikawa, Rokusuke
AU - Izumi, Taisuke
AU - Yamada, Eri
AU - Nakano, Yusuke
AU - Misawa, Naoko
AU - Ren, Fengrong
AU - Carpenter, Michael A.
AU - Ikeda, Terumasa
AU - Münk, Carsten
AU - Harris, Reuben S.
AU - Miyazawa, Takayuki
AU - Koyanagi, Yoshio
AU - Sato, Kei
N1 - Publisher Copyright:
© 2015, American Society for Microbiology.
PY - 2016
Y1 - 2016
N2 - 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 hapVemerged approximately 60,000 years ago. Taken together, these findings suggest that feline A3Z3 hapVmay 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.
AB - 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 hapVemerged approximately 60,000 years ago. Taken together, these findings suggest that feline A3Z3 hapVmay 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.
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U2 - 10.1128/JVI.02612-15
DO - 10.1128/JVI.02612-15
M3 - Article
C2 - 26491161
AN - SCOPUS:84953889018
SN - 0022-538X
VL - 90
SP - 474
EP - 485
JO - Journal of virology
JF - Journal of virology
IS - 1
ER -