| Mar 22, 2017 Feline immunodeficiency virus evolutionarily acquires two proteins, Vif and protease, capable of antagonizing feline APOBEC3 |
Rokusuke Yoshikawa1,a, Junko S. Takeuchi1,b, Eri Yamada1, Yusuke Nakano1, Naoko Misawa1, Yuichi Kimura1, Fengrong Ren2, Takayuki Miyazawa3, Yoshio Koyanagi1, and Kei Sato4
1) Laboratory of Systems Virology, Institute for Frontiers Life and Medical Sciences, Kyoto University, Kyoto 6068507, Japan
2) Department of Bioinformatics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 1138510, Japan
3) Laboratory of Virus-Host Coevolution, Institute for Frontiers Life and Medical Sciences, Kyoto University,
4) CREST, JST, Saitama 3220012, Japan.
Present affiliations:
a) Institute of Tropical Medicine, Nagasaki University, Nagasaki 8528523, Japan
b) Department of Virology II, National Institute of Infectious Diseases, Tokyo 1628640, Japan.
J Virol. 2017 Mar 22. pii: JVI.00250-17. doi: 10.1128/JVI.00250-17.
Abstract
The interplay between viral and host proteins has been well studied to elucidate virus-host interactions and their relevance to virulence. Mammalian genes encode apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) proteins, which act as intrinsic restriction factors against lentiviruses. To overcome APOBEC3-mediated anti-viral actions, lentiviruses have evolutionarily acquired an accessory protein, viral infectivity factor (Vif), and Vif degrades host APOBEC3 proteins via a ubiquitin/proteasome-dependent pathway. Although Vif-APOBEC3 interaction and its evolutionary significance, particularly those of primate lentiviruses (including HIV) and primates (including humans), have been well investigated, those of non-primate lentiviruses and non-primates are poorly understood. Moreover, the factors that determine lentiviral pathogenicity remain unclear. Here, we focus on feline immunodeficiency virus (FIV), a pathogenic lentivirus in domestic cats, and the interaction between FIV Vif and feline APOBEC3 in terms of viral virulence and evolution. We reveal the significantly reduced diversity of FIV subtype B compared to that of other subtypes, which may associate with the low pathogenicity of this subtype. We also demonstrate that FIV subtype B Vif is less active with regards to feline APOBEC3 degradation. More intriguingly, we further reveal that FIV protease cleaves feline APOBEC3 in released virions. Taken together, our findings provide evidence that a lentivirus encodes two types of anti-APOBEC3 factors, Vif and viral protease, and further suggest that Vif potently modulates lentiviral pathogenicity.
Figure: Schematic of putative scenario for FIV Vif evolution.
Our findings suggest that the anti-feline APOBEC3 activity of FIV Vif subtype B was attenuated after divergence from subtype D and is evolutionarily conserved. This is the first study to propose the potential of lentiviruses to control their pathogenicity by attenuating the ability of Vif to antagonize the actions of host anti-viral APOBEC3 proteins.