Quantification of Deaminase Activity-Dependent and -Independent Restriction of HIV-1 Replication Mediated by APOBEC3F and APOBEC3G through Experimental-Mathematical Investigation
- Tomoko Kobayashia,
- Yoshiki Koizumib,
- Junko S. Takeuchia,
- Naoko Misawaa,
- Yuichi Kimuraa,
- Satoru Moritac,
- Kazuyuki Aiharad,e,
- Yoshio Koyanagia,
- Shingo Iwamif and
- Kei Satoa
- aLaboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Japan
- bSchool of Medicine, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa, Japan
- cDepartment of Mathematical and Systems Engineering, Shizuoka University, Shizuoka, Japan
- dInstitute of Industrial Science, The University of Tokyo, Tokyo, Japan
- eGraduate School of Information Science and Technology, The University of Tokyo, Tokyo, Japan
- fDepartment of Biology, Faculty of Sciences, Kyushu University, Fukuoka, Japan
- S. R. Ross, Editor
ABSTRACT
APOBEC3F and APOBEC3G cytidine deaminases potently inhibit human immunodeficiency virus type 1 (HIV-1) replication by enzymatically inserting G-to-A mutations in viral DNA and/or impairing viral reverse transcription independently of their deaminase activity. Through experimental and mathematical investigation, here we quantitatively demonstrate that 99.3% of the antiviral effect of APOBEC3G is dependent on its deaminase activity, whereas 30.2% of the antiviral effect of APOBEC3F is attributed to deaminase-independent ability. This is the first report quantitatively elucidating how APOBEC3F and APOBEC3G differ in their anti-HIV-1 modes.
FOOTNOTES
- Received 8 January 2014.
- Accepted 3 March 2014.
- Address correspondence to Kei Sato, ksato{at}virus.kyoto-u.ac.jp, or Shingo Iwami, siwami{at}kyushu-u.org.
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Tomoko Kobayashi and Yoshiki Koizumi contributed equally to this study.
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Published ahead of print 12 March 2014
- Copyright © 2014, American Society for Microbiology. All Rights Reserved.
