Skip to main content

Advertisement

SpringerLink
Log in

TRIM5 gene polymorphisms in HIV-1-infected patients and healthy controls from Northeastern Brazil

  • Brief Report
  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

Humans show heterogeneity in vulnerability to HIV-1 infection, partially under control of genes involved in host immunity and virus replication. TRIM5α protein has restriction activity against replication of many retroviruses. Human TRIM5 gene single nucleotide polymorphisms have been reported as involved in susceptibility to HIV-1 infection. We recruited 213 HIV-1-positive patients and 234 healthy uninfected controls from Northeast Brazil; two non-synonymous variants at exon 2, rs3740996 (H43Y) and rs10838525 (R136Q), and one regulatory polymorphism (rs16934386) at 5′UTR region of TRIM5 were analyzed. The R136Q variation presented significant differences between HIV-1-positive patients and healthy controls. The 136Q allele and the 136QQ genotype were more frequent in healthy controls (32.7 and 10.2 %, respectively) than in HIV-1-positive patients (136Q allele: 24.4 %; OR 0.66; CI 95 % 0.49–0.90; p value = 0.008/136QQ genotype: 4.2 %; OR 0.33; CI 95 % 0.13–0.79, p = 0.008) also after adjusting for age and sex. We also stratified our findings according to the presence of CCR5Δ32 variation, but the results remained the same. We observed that rs10838525 (R136Q) and rs3740996 (H43Y) were in linkage disequilibrium (D′ = 0.71), forming four possible haplotypes. The H43–136Q haplotype was significantly more frequent in healthy controls (28.2 %) than in HIV-positive patients (21.4 %; OR 0.69; CI 95 % 0.50–0.96; p = 0.022). An increased frequency of allele (136Q) and genotype (136QQ) of the non-synonymous rs10838525 (R136Q) variant and the haplotype (43H-136Q) was observed among healthy controls individuals. Being aware of the limitation of this study (unavailability of exposed but uninfected individuals), we hypothesize a potential role for TRIM5 variations in the protection against HIV-1 infection.

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

References

  1. Wolf D, Goff SP. Host restriction factors blocking retroviral replication. Annu Rev Genet. 2008;42:143–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Stremlau M, Owens CM, Perron MJ, Kiessling M, Autissier P, Sodroski J. The cytoplasmic body component TRIM5α restricts HIV-1 infection in Old World monkeys. Nature. 2004;427:848–53.

    Article  CAS  PubMed  Google Scholar 

  3. Battivelli E, Migraine J, Lecossier D, Yeni P, Clavel F, Hance AJ. Gag cytotoxic T lymphocyte escape mutations can increase sensitivity of HIV-1 to human TRIM5alpha, linking intrinsic and acquired immunity. J Virol. 2011;85:11846–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Chatterji U, Bobardt MD, Gaskill P, Sheeter D, Fox H, Gallay PA. Trim5alpha accelerates degradation of cytosolic capsid associated with productive HIV-1 entry. J Biol Chem. 2006;281:37025–33.

    Article  CAS  PubMed  Google Scholar 

  5. Stremlau M, Perron M, Lee M, Li Y, Song B, Javanbakht H, et al. Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5alpha restriction factor. Proc Natl Acad Sci USA. 2006;103:5514–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L, et al. The tripartite motif family identifies cell compartments. EMBO J. 2001;20:2140–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Javanbakht H, Diaz-Griffero F, Stremlau M, Si Z, Sodroski J. The contribution of RING and B-box 2 domains to retroviral restriction mediated by monkey TRIM5alpha. J Biol Chem. 2005;280:26933–40.

    Article  CAS  PubMed  Google Scholar 

  8. Diaz-Griffero F, Qin X, Hayashi F, Kigawa T, Finzi A, Sarnak Z, et al. A B-box 2 surface patch important for TRIM5alpha self-association, capsid binding avidity, and retrovirus restriction. J Virol. 2009;83:10737–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Maillard PV, Ecco G, Ortiz M, Trono D. The specificity of TRIM5 alpha-mediated restriction is influenced by its coiled-coil domain. J Virol. 2010;84:5790–801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Mische CC, Javanbakht H, Song B, Diaz-Griffero F, Stremlau M, Strack B, et al. Retroviral restriction factor TRIM5alpha is a trimer. J Virol. 2005;79:14446–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Javanbakht H, Yuan W, Yeung DF, Song B, Diaz-Griffero F, Li Y, et al. Characterization of TRIM5alpha trimerization and its contribution to human immunodeficiency virus capsid binding. Virology. 2006;353:234–46.

    Article  CAS  PubMed  Google Scholar 

  12. Li X, Gold B, O’hUigin C, Diaz-Griffero F, Song B, Si Z, et al. Unique features of TRIM5alpha among closely related human TRIM family members. Virology. 2007;360:419–33.

    Article  CAS  PubMed  Google Scholar 

  13. Ohkura S, Yap MW, Sheldon T, Stoye JP. All three variable regions of the TRIM5alpha B30.2 domain can contribute to the specificity of retrovirus restriction. J Virol. 2006;80:8554–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Stremlau M, Perron M, Welikala S, Sodroski J. Species-specific variation in the B30.2(SPRY) domain of TRIM5alpha determines the potency of human immunodeficiency virus restriction. Society. 2005;79:3139–45.

    CAS  Google Scholar 

  15. Javanbakht H, An P, Gold B, Petersen DC, O’Huigin C, Nelson GW, et al. Effects of human TRIM5alpha polymorphisms on antiretroviral function and susceptibility to human immunodeficiency virus infection. Virology. 2006;354:15–27.

    Article  CAS  PubMed  Google Scholar 

  16. Nakayama EE, Carpentier W, Costagliola D, Shioda T, Iwamoto A, Debre P, et al. Wild type and H43Y variant of human TRIM5alpha show similar anti-human immunodeficiency virus type 1 activity both in vivo and in vitro. Immunogenetics. 2007;59:511–5.

    Article  CAS  PubMed  Google Scholar 

  17. Price H, Lacap P, Tuff J, Wachihi C, Kimani J, Terry B, et al. A TRIM5alpha exon 2 polymorphism is associated with protection from HIV-1 infection in the Pumwani sex worker cohort. AIDS. 2010;24:1813–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. van Manen D, Rits MAN, Beugeling C, van Dort K, Schuitemaker H, Kootstra NA. The effect of Trim5 polymorphisms on the clinical course of HIV-1 infection. PLoS Pathog. 2008;4:e18.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Speelmon EC, Livingston-rosanoff D, Li S, Vu Q, Bui J, Geraghty DE, et al. Genetic association of the antiviral restriction factor TRIM5 α with human immunodeficiency virus type 1 infection. J Virol. 2006;80:24.

    Article  Google Scholar 

  20. Sawyer SL, Wu LI, Akey JM, Emerman M, Malik HS. High-frequency persistence of an impaired allele of the retroviral defense gene TRIM5alpha in humans. Curr Biol. 2006;16:95–100.

    Article  CAS  PubMed  Google Scholar 

  21. Goldschmidt V, Bleiber G, May M, Martinez R, Ortiz M, Telenti A. Role of common human TRIM5alpha variants in HIV-1 disease progression. Retrovirology. 2006;3:54.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Nakajima T, Nakayama EE, Kaur G, Terunuma H, Mimaya J, Ohtani H, et al. Impact of novel TRIM5alpha variants, Gly110Arg and G176del, on the anti-HIV-1 activity and the susceptibility to HIV-1 infection. AIDS. 2009;23:2091–100.

    Article  CAS  PubMed  Google Scholar 

  23. Liu F-L, Qiu Y-Q, Li H, Kuang Y-Q, Tang X, Cao G, et al. An HIV-1 resistance polymorphism in TRIM5α gene among Chinese intravenous drug users. J Acquir Immune Defic Syndr. 2011;56:306–11.

    Article  CAS  PubMed  Google Scholar 

  24. Coelho A, Moura R, Cavalcanti C, Guimaraes R, Sandrin-Garcia P, Crovella S, et al. A rapid screening of ancestry for genetic association studies in an admixed population from Pernambuco. Braz Genet Mol Res. 2015;14:2876–84.

    Article  CAS  Google Scholar 

  25. An P, Winkler CA. Host genes associated with HIV/AIDS: advances in gene discovery. Trends Genet. 2010;26:119–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Picchio GR, Gulizia RJ, Mosier DE. Chemokine receptor CCR5 genotype influences the kinetics of human immunodeficiency virus type 1 infection in human PBL-SCID mice. J Virol. 1997;71:7124–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005;21:263–5.

    Article  CAS  PubMed  Google Scholar 

  28. R Development Core Team. R: a language and environment for statistical computing. R foundation for statistical computing, Vienna, Austria. http://www.R-project.org/. R Found. Stat. Comput. Vienna, Austria. 2013.

  29. Geretti AM. HIV-1 subtypes: epidemiology and significance for HIV management. Curr Opin Infect Dis. 2006;19:1–7.

    Article  PubMed  Google Scholar 

  30. Cavalcanti AMS, de Brito AM, Salustiano DM, de Lima KO, da Silva SP, Diaz RS, et al. Primary resistance of HIV to antiretrovirals among individuals recently diagnosed at voluntary counselling and testing centres in the metropolitan region of Recife, Pernambuco. Mem Inst Oswaldo Cruz. 2012;107:450–7.

    Article  PubMed  Google Scholar 

  31. Cavalcanti AMS, Lacerda HR, De Brito AM, Pereira S, Medeiros D, Oliveira S. Antiretroviral resistance in individuals presenting therapeutic failure and subtypes of the human immunodeficiency virus type 1 in the Northeast Region of Brazil. Mem Inst Oswaldo Cruz. 2007;102:785–92.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors wish to thank the Post-graduation Program in Genetics of Federal University of Pernambuco, the Laboratory of Immunopathology Keizo Asami, the Institute of Integral Medicine of Pernambuco (IMIP), the Hemope and the Department of Genetics of Federal University of Pernambuco for technical and scientific support. We also thank to “Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco” (FACEPE) (APQ-0599-2.02/14), “Programa de Pós-Doutorado Júnior from Conselho Nacional de Desenvolvimento Científico e Tecnológico” (PDJ/CNPq nº402374/2014-2) and “Coordenação de Aperfeiçoamento de Pessoal de Nível Superior” (CAPES) for financial support.

Author information

Authors and Affiliations

  1. Department of Genetics, Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego, s/no, Recife, Pernambuco, CEP 50.670-420, Brazil

    Ronaldo Celerino da Silva, Antonio Victor Campos Coelho, Sergio Crovella & Rafael Lima Guimarães

  2. Laboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco (UFPE), Recife, Brazil

    Ronaldo Celerino da Silva, Antonio Victor Campos Coelho, Lucas André Cavalcanti Brandão, Sergio Crovella & Rafael Lima Guimarães

  3. Institute of Integral Medicine Professor Fernando Figueira (IMIP), Recife, Brazil

    Luiz Cláudio Arraes

  4. Department of Pathology, Federal University of Pernambuco (UFPE), Recife, Brazil

    Lucas André Cavalcanti Brandão

Authors
  1. Ronaldo Celerino da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antonio Victor Campos Coelho
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luiz Cláudio Arraes
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lucas André Cavalcanti Brandão
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sergio Crovella
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rafael Lima Guimarães
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ronaldo Celerino da Silva.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 45 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Celerino da Silva, R., Coelho, A.V.C., Arraes, L.C. et al. TRIM5 gene polymorphisms in HIV-1-infected patients and healthy controls from Northeastern Brazil. Immunol Res 64, 1237–1242 (2016). https://doi.org/10.1007/s12026-016-8810-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12026-016-8810-1

Keywords

Search

Navigation