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

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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.

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References

  1. Bogerd HP, Doehle BP, Wiegand HL, Cullen BR (2004) A single amino acid difference in the host apobec3g protein controls the primate species specificity of hiv type 1 virion infectivity factor. Proc Natl Acad Sci USA 101(11):3770–3774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Compton AA, Hirsch VM, Emerman M (2012) The host restriction factor APOBEC3G and retroviral Vif protein coevolve due to ongoing genetic conflict. Cell Host Microbe 11:91–98

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Compton AA, Emerman M (2013) Convergence and divergence in the evolution of the APOBEC3G-Vif interaction reveal ancient origins of simian immunodeficiency viruses. PLoS Pathog 9:e1003135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Gandhi SK, Siliciano JD, Bailey JR, Siliciano RF, Blankson JN (2008) Role of APOBEC3G/F-mediated hypermutation in the control of human immunodeficiency virus type 1 in elite suppressors. J Virol 82:3125–3130

    Article  CAS  PubMed  Google Scholar 

  5. Goujon C, Moncorgé O, Bauby H, Doyle T, Ward CC, Schaller T, Hué S, Barclay WS, Schulz R, Malim MH (2013) Human MX2 is an interferon-induced post-entry inhibitor of HIV-1 infection. Nature 502:559–562

    Article  CAS  PubMed  Google Scholar 

  6. Harris RS, Liddament MT (2004) Retroviral restriction by APOBEC proteins. Nat Rev Immunol 4:868–877

    Article  CAS  PubMed  Google Scholar 

  7. Hrecka K, Hao C, Gierszewska M, Swanson SK, Kesik-Brodacka M, Srivastava S, Florens L, Washburn MP, Skowronski J (2011) Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein. Nature 474:658–661

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hu SL (2005) Non-human primate models for AIDS vaccine research. Curr Drug Targets Infect Disord 5:193–201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Krupp A, McCarthy KR, Ooms M, Letko M, Morgan JS, Simon V, Johnson WE (2013) APOBEC3G polymorphism as a selective barrier to cross-species transmission and emergence of pathogenic SIV and AIDS in a primate host. PLoS Pathog 9:e1003641

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Laguette N, Sobhian B, Casartelli N, Ringeard M, Chable-Bessia C, Ségéral E, Yatim A, Emiliani S, Schwartz O, Benkirane M (2011) SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. Nature 474:654–657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Letko M, Silvestri G, Hahn BH, Bibollet-Ruche F, Gokcumen O, Simon V, Ooms M (2013) Vif Proteins from diverse primate lentiviral lineages use the same binding site in APOBEC3G. J Virol 87:11861–11871

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Navarro F, Bollman B, Chen H, Malim MH, Bieniasz PD (2012) HIV restriction factors and mechanisms of eva-sion. Cold Spring Harb Perspect Med 2(a0):06940

    Google Scholar 

  13. Marin M, Rose KM, Kozak SL, Kabat D (2003) HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation. Nat Med 9:1398–1403

    Article  PubMed  Google Scholar 

  14. Neil SJ, Zang T, Bieniasz PD (2008) Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 451:425–430

    Article  CAS  PubMed  Google Scholar 

  15. Saifuddin M, Spear GT, Chang C, Roebuck KA (2000) Expression of mhc class ii in t cells is associated with increased hiv-1 expression. Clin Exp Immunol 121(2):324–331

    Article  Google Scholar 

  16. Schröfelbauer B, Senger T, Manning G, Landau NR (2006) Mutational alteration of human immunodeficiency virus type 1 vif allows for functional interaction with nonhuman primate apobec3g. J Virol 80(12):5984–5991

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Sheehy AM, Gaddis NC, Choi JD, Malim MH (2002) Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 418:646–650

    Article  CAS  PubMed  Google Scholar 

  18. Sheehy AM, Gaddis NC, Malim MH (2003) The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif. Nat Med 9:1404–1407

    Article  CAS  PubMed  Google Scholar 

  19. Stremlau M, Owens CM, Perron MJ, Kiessling M, Autissier P, Sodroski J (2004) The cytoplasmic body component TRIM5alpha restricts HIV-1 infection in old world monkeys. Nature 427:848–853

    Article  CAS  PubMed  Google Scholar 

  20. Smith JL, Izumi T, Borbet TC, Hagedorn AN, Pathak VK (2014) HIV-1 and HIV-2 vif interact with human APOBEC3 proteins using completely different determinants. J Virol 88:9893–9908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Suspène R, Sommer P, Henry M, Ferris S, Guétard D, Pochet S, Chester A, Navaratnam N, Wain-Hobson S, Vartanian JP (2004) APOBEC3G is a single-stranded DNA cytidine deaminase and functions independently of HIV reverse transcriptase. Nucleic Acids Res 32:2421–2429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ulenga NK, Sarr AD, Thakore-Meloni S, Sankalé JL, Eisen G, Kanki PJ (2008) Relationship between human immunodeficiency type 1 infection and expression of human APOBEC3G and APOBEC3F. J Infect Dis 198:486–492

    Article  PubMed  Google Scholar 

  23. Weiler A, May GE, Qi Y, Wilson N, Watkins DI (2006) Polymorphisms in eight host genes associated with control of HIV replication do not mediate elite control of viral replication in SIV-infected Indian rhesus macaques. Immunogenetics 58:1003–1009

    Article  CAS  PubMed  Google Scholar 

  24. Wonderlich ER, Leonard JA, Kulpa DA, Leopold KE, Norman JM, Collins KL (2011) Adp ribosylation factor 1 activity is required to recruit ap-1 to the major histocompatibility complex class I (MHC-I) cytoplasmic tail and disrupt MHC-I trafficking in HIV-1-infected primary t cells. J Virol 85(23):12216–12226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Xie W, Agniel D, Shevchenko A, Malov SV, Svitin A, Cherkasov N et al (2017) Genome-wide analyses reveal gene influence on HIV disease progression and HIV-1C acquisition in southern africa. AIDS Res Hum Retroviruses 33(6):597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Yu Q, König R, Pillai S, Chiles K, Kearney M, Palmer S, Richman D, Coffin JM, Landau NR (2004) Single-strand specificity of APOBEC3G accounts for minus-strand deamination of the HIV genome. Nat Struct Mol Biol 11:435–442

    Article  CAS  PubMed  Google Scholar 

  27. Yu X, Yu Y, Liu B, Luo K, Kong W, Mao P, Yu XF (2003) Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex. Science 302:1056–1060

    Article  CAS  PubMed  Google Scholar 

  28. Zhang H, Yang B, Pomerantz RJ, Zhang C, Arunachalam SC, Gao L (2003) The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA. Nature 424:94–98

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Zhang HL, Liu FL, Jin YB, Deng Q, Liu BL, Zhuo M, Liu XH, Zheng YT, Ling F (2015) The effects of TRIM5α polymorphism on HIV-2ROD and SIVmac239replication in PBMCs from Chinese rhesus macaques andVietnamese-origin cynomolgus macaques. Virology 487:222–229

    Article  CAS  PubMed  Google Scholar 

  30. Zhang ZL, Gu QY, Vasudevan AAJ, Hain A, Kloke BB, Hashemina S, Mulnaes D, Sato K, Cichutek K, Häussinger DG, Bravo LHJ, Smits S, Gohlke H, Münk C (2016) Determinants of FIV and HIV Vif sensitivity of feline APOBEC3 restriction factors. Retrovirology 13:46

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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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.

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Authors and Affiliations

  1. School of Biology and Biological Engineering, South China University of Technology, Guangzhou, 510006, People’s Republic of China

    Zhi-Qiang Jiang, Xu-Rong Yao, Hang Yu, Yue-Er Lu, Bei-Lei Liu, Min Zhuo & Fei Ling

  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 Sciences, Kunming, Yunnan, People’s Republic of China

    Feng-Liang Liu & Yong-Tang Zheng

  3. Institute of Clinical Medicine, First People’s Hospital of Foshan, Foshan, 528000, Guangdong, People’s Republic of China

    Ya-Bin Jin

Authors
  1. Zhi-Qiang Jiang
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  2. Xu-Rong Yao
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  3. Hang Yu
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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.

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Correspondence to Feng-Liang Liu or Fei Ling.

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Jiang, ZQ., Yao, XR., Yu, H. et al. Polymorphisms in the APOBEC3G gene of Chinese rhesus macaques affect resistance to ubiquitination and degradation mediated by HIV-2 Vif. Arch Virol 164, 1353–1360 (2019). https://doi.org/10.1007/s00705-019-04194-0

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  • DOI: https://doi.org/10.1007/s00705-019-04194-0