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Archives of Virology

, Volume 164, Issue 5, pp 1353–1360 | Cite as

Polymorphisms in the APOBEC3G gene of Chinese rhesus macaques affect resistance to ubiquitination and degradation mediated by HIV-2 Vif

  • Zhi-Qiang Jiang
  • Xu-Rong Yao
  • Hang Yu
  • Yue-Er Lu
  • Bei-Lei Liu
  • Feng-Liang LiuEmail author
  • Ya-Bin Jin
  • Min Zhuo
  • Yong-Tang Zheng
  • Fei LingEmail author
Original Article
  • 151 Downloads

Abstract

Animal cells have multiple innate effector mechanisms that inhibit viral replication. For the pathogenic retrovirus human immunodeficiency virus 1 (HIV-1), there are widely expressed restriction factors, such as APOBEC3 proteins, tetherin/BST2, SAMHD1 and MX2, as well as TRIM5α. We previously found that the TRIM5α gene clearly affects SIVmac or HIV-2 replication, but the major determinant of the combinatorial effect caused by multiple host restriction factors is still not fully clear. APOBEC3G (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G), a host restriction factor that restricts HIV replication by causing cytosine deamination, can be targeted and degraded by the SIV/HIV-1/HIV-2 accessory protein Vif. Although rhesus macaques are widely used in HIV/AIDS research, little is known regarding the impact of APOBEC3G gene polymorphisms on viral Vif-mediated ubiquitin degradation in Chinese-origin rhesus macaques. In this study, we therefore genotyped APOBEC3G in 35 Chinese rhesus macaques. We identified a novel transcript and 27 APOBEC3G polymorphisms, including 20 non-synonymous variants and 7 synonymous mutation sites, of which 10 were novel. According to the predicted structure of the A3G protein, we predicted that the E88K and G212D mutations, both on the surface of the A3G protein, would have a significant effect on Vif-induced A3G degradation. However, an in vitro overexpression assay showed that these mutations did not influence HIV-2-Vif-mediated degradation of APOBEC3G. Unexpectedly, another polymorphism L71R, conferred resistance to Vif-mediated ubiquitin degradation, strongly suggesting that L71R might play an important role in antiviral defense mechanisms.

Notes

Acknowledgments

This project was granted by the National Natural Science Foundation of China (31271322; 31401088; 81202366; 81172876) and the Natural Science Foundation of Guangdong Province (2015A030302010; 2014KZDXM009). We would like to thank ZeLi Zhang (Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich-Heine-University Düsseldorf) for gracious donation of the HIV-2 Vif expression plasmids.

Author contributions

FL and YTZ conceived and designed the experiments. XRY, HLZ, HY, JTO, and ZMW performed the experiments. YBJ, XRY, and HY analyzed the data. BLL and MZ contributed reagents/materials/analysis tools. XRY and FLL wrote the paper. YEL, YTZ, and FL edited the paper.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

705_2019_4194_MOESM1_ESM.pdf (98 kb)
Supplementary material 1 (PDF 98 kb)
705_2019_4194_MOESM2_ESM.docx (30 kb)
Supplementary material 2 (DOCX 29 kb)

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.School of Biology and Biological EngineeringSouth China University of TechnologyGuangzhouPeople’s Republic of China
  2. 2.Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of SciencesKunmingPeople’s Republic of China
  3. 3.Institute of Clinical Medicine, First People’s Hospital of FoshanFoshanPeople’s Republic of China

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