Skip to main content

Advertisement

SpringerLink
Log in

Association of single nucleotide polymorphisms of APOBEC3G with susceptibility to HIV-1 infection and disease progression among men engaging in homosexual activity in northern China

  • Original Article
  • Published:
Archives of Virology Aims and scope Submit manuscript

Abstract

Men who have sex with men (MSM) are at high risk of HIV infection. The APOBEC3G (apolipoprotein B mRNA editing catalytic polypeptide 3G) protein is a component of innate antiviral immunity that inhibits HIV-1 replication. In the present study, a total of 483 HIV-1 seropositive men and 493 HIV-1 seronegative men were selected to investigate the association between single nucleotide polymorphisms (SNPs) of the APOBEC3G gene and susceptibility to HIV-1 infection and AIDS progression among MSM residing in northern China. Genotyping of four SNPs (rs5757465, rs3736685, rs8177832, and rs2899313) of the APOBEC3G was performed using the SNPscan™ Kit, while the rs2294367 polymorphism was genotyped using the SNaPshot multiplex system. Our results disclosed no association between the SNPs of APOBEC3G and susceptibility to HIV-1, or effects of these polymorphisms on the CD4+ T cell count or clinical phase of disease. A meta-analysis of 1624 men with HIV-1 infection and 1523 controls suggested that the association between rs8177832 and susceptibility was not significant. However, we observed a trend towards association with HIV-1 infection for haplotype TTACA (p = 0.082). The potential role of variants of APOBEC3G in HIV-1/AIDS warrants further investigation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Reference

  1. An P, Bleiber G, Duggal P, Nelson G, May M, Mangeat B, Alobwede I, Trono D, Vlahov D, Donfield S, Goedert JJ, Phair J, Buchbinder S, O’Brien SJ, Telenti A, Winkler CA (2004) APOBEC3G genetic variants and their influence on the progression to AIDS. J Virol 78:11070–11076

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. An P, Penugonda S, Thorball CW, Bartha I, Goedert JJ, Donfield S, Buchbinder S, Binns-Roemer E, Kirk GD, Zhang W, Fellay J, Yu XF, Winkler CA (2016) Role of APOBEC3F gene variation in HIV-1 disease progression and pneumocystis pneumonia. PLoS Genet 12:e1005921

    Article  PubMed  PubMed Central  Google Scholar 

  3. Anderson JL, Hope TJ (2008) APOBEC3G restricts early HIV-1 replication in the cytoplasm of target cells. Virology 375:1–12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Beyrer C, Baral SD, van Griensven F, Goodreau SM, Chariyalertsak S, Wirtz AL, Brookmeyer R (2012) Global epidemiology of HIV infection in men who have sex with men. Lancet 380:367–377

    Article  PubMed  PubMed Central  Google Scholar 

  5. Bishop KN, Verma M, Kim EY, Wolinsky SM, Malim MH (2008) APOBEC3G inhibits elongation of HIV-1 reverse transcripts. PLoS Pathogens 4:e1000231

    Article  PubMed  PubMed Central  Google Scholar 

  6. 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 101:3770–3774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Bunupuradah T, Imahashi M, Iampornsin T, Matsuoka K, Iwatani Y, Puthanakit T, Ananworanich J, Sophonphan J, Mahanontharit A, Naoe T, Vonthanak S, Phanuphak P, Sugiura W, Team PS (2012) Association of APOBEC3G genotypes and CD4 decline in Thai and Cambodian HIV-infected children with moderate immune deficiency. AIDS Res Ther 9:34

    Article  PubMed  PubMed Central  Google Scholar 

  8. Compaore TR, Soubeiga ST, Ouattara AK, Obiri-Yeboah D, Tchelougou D, Maiga M, Assih M, Bisseye C, Bakouan D, Compaore IP, Dembele A, Martinson J, Simpore J (2016) APOBEC3G variants and protection against HIV-1 infection in Burkina Faso. PloS One 11:e0146386

    Article  PubMed  PubMed Central  Google Scholar 

  9. Conticello SG, Harris RS, Neuberger MS (2003) The Vif protein of HIV triggers degradation of the human antiretroviral DNA deaminase APOBEC3G. Current Biol CB 13:2009–2013

    Article  CAS  Google Scholar 

  10. De Maio FA, Rocco CA, Aulicino PC, Bologna R, Mangano A, Sen L (2011) Effect of HIV-1 Vif variability on progression to pediatric AIDS and its association with APOBEC3G and CUL5 polymorphisms. Infect Genet Evol J Mol Epidemiol Evol Genet Infect Dis 11:1256–1262

    Article  Google Scholar 

  11. De Maio FA, Rocco CA, Aulicino PC, Bologna R, Mangano A, Sen L (2012) APOBEC3-mediated editing in HIV type 1 from pediatric patients and its association with APOBEC3G/CUL5 polymorphisms and Vif variability. AIDS Res Hum Retrovir 28:619–627

    Article  PubMed  Google Scholar 

  12. Do H, Vasilescu A, Diop G, Hirtzig T, Heath SC, Coulonges C, Rappaport J, Therwath A, Lathrop M, Matsuda F, Zagury JF (2005) Exhaustive genotyping of the CEM15 (APOBEC3G) gene and absence of association with AIDS progression in a French cohort. J Infect Dis 191:159–163

    Article  CAS  PubMed  Google Scholar 

  13. Hallman DM, Boerwinkle E, Saha N, Sandholzer C, Menzel HJ, Csazar A, Utermann G (1991) The apolipoprotein E polymorphism: a comparison of allele frequencies and effects in nine populations. Am J Hum Genet 49:338–349

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Harris RS, Bishop KN, Sheehy AM, Craig HM, Petersen-Mahrt SK, Watt IN, Neuberger MS, Malim MH (2003) DNA deamination mediates innate immunity to retroviral infection. Cell 113:803–809

    Article  CAS  PubMed  Google Scholar 

  15. Iwabu Y, Kinomoto M, Tatsumi M, Fujita H, Shimura M, Tanaka Y, Ishizaka Y, Nolan D, Mallal S, Sata T, Tokunaga K (2010) Differential anti-APOBEC3G activity of HIV-1 Vif proteins derived from different subtypes. J Biol Chem 285:35350–35358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Jia Y, Aliyu MH, Jennifer Huang Z (2014) Dynamics of the HIV epidemic in MSM. BioMed Res Int 2014:497543

    PubMed  PubMed Central  Google Scholar 

  17. Lecossier D, Bouchonnet F, Clavel F, Hance AJ (2003) Hypermutation of HIV-1 DNA in the absence of the Vif protein. Science 300:1112

    Article  CAS  PubMed  Google Scholar 

  18. Li X, Lu H, Cox C, Zhao Y, Xia D, Sun Y, He X, Xiao Y, Ruan Y, Jia Y, Shao Y (2014) Changing the landscape of the HIV epidemic among MSM in China: results from three consecutive respondent-driven sampling surveys from 2009 to 2011. BioMed Res Int 2014:563517

    PubMed  PubMed Central  Google Scholar 

  19. Luo K, Wang T, Liu B, Tian C, Xiao Z, Kappes J, Yu XF (2007) Cytidine deaminases APOBEC3G and APOBEC3F interact with human immunodeficiency virus type 1 integrase and inhibit proviral DNA formation. J Virol 81:7238–7248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Mangeat B, Turelli P, Caron G, Friedli M, Perrin L, Trono D (2003) Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. Nature 424:99–103

    Article  CAS  PubMed  Google Scholar 

  21. 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  CAS  PubMed  Google Scholar 

  22. Naruse TK, Sakurai D, Ohtani H, Sharma G, Sharma SK, Vajpayee M, Mehra NK, Kaur G, Kimura A (2016) APOBEC3H polymorphisms and susceptibility to HIV-1 infection in an Indian population. J Hum Genet 61:263–265

    Article  CAS  PubMed  Google Scholar 

  23. Punyacharoensin N, Edmunds WJ, De Angelis D, Delpech V, Hart G, Elford J, Brown A, Gill N, White RG (2015) Modelling the HIV epidemic among MSM in the United Kingdom: quantifying the contributions to HIV transmission to better inform prevention initiatives. Aids 29:339–349

    PubMed  Google Scholar 

  24. Rathore A, Chatterjee A, Yamamoto N, Dhole TN (2008) Absence of H186R polymorphism in exon 4 of the APOBEC3G gene among North Indian individuals. Genet Test 12:453–456

    Article  CAS  PubMed  Google Scholar 

  25. Reddy K, Winkler CA, Werner L, Mlisana K, Abdool Karim SS, Ndung’u T, Team CAIS (2010) APOBEC3G expression is dysregulated in primary HIV-1 infection and polymorphic variants influence CD4+ T-cell counts and plasma viral load. Aids 24:195–204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Schrofelbauer B, Chen D, Landau NR (2004) A single amino acid of APOBEC3G controls its species-specific interaction with virion infectivity factor (Vif). Proc Natl Acad Sci USA 101:3927–3932

    Article  PubMed  PubMed Central  Google Scholar 

  27. Shao B, Li WJ, Liu T, Li QH, Li H, Chang ML, Huang CQ, Wang FX, Wang BY (2013) Subtype B was the dominant strain among HIV type 1 infections except for the population of men who have sex with men in Harbin City, China. AIDS Res Hum Retrovir 29:1260–1264

    Article  PubMed  PubMed Central  Google Scholar 

  28. 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 

  29. 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 

  30. Singh KK, Wang Y, Gray KP, Farhad M, Brummel S, Fenton T, Trout R, Spector SA (2013) Genetic variants in the host restriction factor APOBEC3G are associated with HIV-1-related disease progression and central nervous system impairment in children. J Acquir Immune Defic Syndr 62:197–203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Slatkin M (1987) Gene flow and the geographic structure of natural populations. Science 236:787–792

    Article  CAS  PubMed  Google Scholar 

  32. Stopak K, de Noronha C, Yonemoto W, Greene WC (2003) HIV-1 Vif blocks the antiviral activity of APOBEC3G by impairing both its translation and intracellular stability. Mol Cell 12:591–601

    Article  CAS  PubMed  Google Scholar 

  33. Su Y, Liu H, Wu J, Zhu L, Wang N (2014) Distribution of HIV-1 genotypes in China: a systematic review. Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi 35:1164–1168

    CAS  PubMed  Google Scholar 

  34. Valcke HS, Bernard NF, Bruneau J, Alary M, Tsoukas CM, Roger M (2006) APOBEC3G genetic variants and their association with risk of HIV infection in highly exposed Caucasians. Aids 20:1984–1986

    Article  CAS  PubMed  Google Scholar 

  35. Xu H, Svarovskaia ES, Barr R, Zhang Y, Khan MA, Strebel K, Pathak VK (2004) A single amino acid substitution in human APOBEC3G antiretroviral enzyme confers resistance to HIV-1 virion infectivity factor-induced depletion. Proc Natl Acad Sci USA 101:5652–5657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Yang B, Chen K, Zhang C, Huang S, Zhang H (2007) Virion-associated uracil DNA glycosylase-2 and apurinic/apyrimidinic endonuclease are involved in the degradation of APOBEC3G-edited nascent HIV-1 DNA. J Biol Chem 282:11667–11675

    Article  CAS  PubMed  Google Scholar 

  37. 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 

  38. 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 

Download references

Author information

Author notes

    Authors and Affiliations

    1. Laboratory of Medical Genetics, Harbin Medical University, Baojian Road 157, Nangang District, Harbin, 150081, People’s Republic of China

      Qiuyan Li, Yuandong Qiao, Guangfa Zhang, Xuelong Zhang, Xueyuan Jia, Haiming Sun, Chuntao Wang & Lidan Xu

    2. Department of Clinical Laboratory, Qiqihar Traditional Chinese Medicine Hospital, Qiqihar, 161000, People’s Republic of China

      Ning He

    Authors
    1. Qiuyan Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Yuandong Qiao
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Guangfa Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Ning He
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Xuelong Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Xueyuan Jia
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Haiming Sun
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Chuntao Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Lidan Xu
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Lidan Xu.

    Ethics declarations

    Funding

    This work was supported by Grants from the National Natural Science Foundation of China (81102278), the China Postdoctoral Science Foundation (20100481019), the Postdoctoral Science Special Foundation of Heilongjiang Province, China (LBH-TZ1208), the Postdoctoral Science Research Foundation of Heilongjiang Province, China (LBH-Q13128), and Wu lien-teh Youth Science Foundation of Harbin Medical University (WLD-QN1405). In addition, we thank Professor Ping Wang for her edition of the manuscript.

    Conflict of interest

    The authors declare that there is no conflict of interest associated with this manuscript.

    Ethical approval

    All procedures performed in study involving human participants were approved by the review board of Harbin Medical University. Written informed consent was obtained from participants.

    Additional information

    Q. Li and Y. Qiao contributed equally to this work.

    Electronic supplementary material

    Below is the link to the electronic supplementary material.

    Supplementary material 1 (DOC 20 kb)

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Li, Q., Qiao, Y., Zhang, G. et al. Association of single nucleotide polymorphisms of APOBEC3G with susceptibility to HIV-1 infection and disease progression among men engaging in homosexual activity in northern China. Arch Virol 162, 259–268 (2017). https://doi.org/10.1007/s00705-016-3080-8

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s00705-016-3080-8

    Keywords

    Search

    Navigation