CCR5-∆32, CCR2-64I, SDF1-3'A, and IFNλ4 rs12979860 and rs8099917 gene polymorphisms in individuals with HIV-1, HIV/HTLV-1, and HIV/HTLV-2 in São Paulo, Brazil


  • Adele Caterino-de-Araujo Instituto Adolfo Lutz, São Paulo, SP, Brasil.
  • Karoline R. Campos Instituto Adolfo Lutz, São Paulo, SP, Brasil.
  • Emylenne C. Cabral-de-Oliveira Instituto Adolfo Lutz, São Paulo, SP, Brasil.
  • Ana Kelly S. Rodrigues Instituto Adolfo Lutz, São Paulo, SP, Brasil.
  • Rafael X. Silva Instituto Adolfo Lutz, São Paulo, SP, Brasil.
  • Bruna V. Azevedo Instituto Adolfo Lutz, São Paulo, SP, Brasil.
  • Rosa M. N. Marcusso Instituto de Infectologia Emilio Ribas, São Paulo, SP, Brasil.



HIV-1, HTLV-1/2, Chemokine, Chemokine receptors, IFNL4, Polymorphisms


Background. Chemokine and chemokine-receptor polymorphisms have been associated with protection against HIV infection and delayed progression to AIDS, whereas polymorphisms in IFNλ4 (formerly IL28B) have been associated with human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy (HAM) development. Evolutionary selection against ancestral genes differs among human populations, resulting in varying risks of acquiring and developing viral diseases. Methods. DNA samples from 434 patients infected with HIV-1 and/or co-infected with HTLV-1/-2, and samples from 74 HIV and HTLV non-infected individuals from São Paulo, Brazil, were divided into five groups: HIV-naïve, n=160; HIV-ART, n=180; HIV/HTLV-1, n=53; HIV/HTLV-2, n=41; and control, n=74. These samples were analyzed for CCR5-∆32 deletion, CCR2-64I, SDF1-3'A, and IFNλ4 rs12979860 and rs8099917 single nucleotide polymorphisms using PCR and PCR-RFLP techniques. These polymorphisms' genotype and allele frequencies were calculated and compared among groups using logistic regression analysis. Results. All polymorphism profiles described in the literature were detected in this study. The wild-type genotype predominated in all genes analyzed except for IFNλ4 rs12979860. Statistical differences in allele frequencies among groups were detected in the CCR5 and CCR2 genes, with a high frequency of ∆32 in HIV-naïve vs. HIV-ART (OR 2.45, P=0.037) and a minus mutant allele A (CCR2-64I) in HIV-naïve vs. HIV/HTLV-1 (OR 1.90, P=0.048), HIV-ART vs. HIV/HTLV-1 (OR 2.62, P=0.003), and HIV/ART vs. HIV/HTLV-2 (OR 2.42, P=0.016). Conclusions. The polymorphism profiles detected in the study groups corroborate the profiles described in racial admixed populations. High CCR2-64I mutant allele frequencies were detected in HIV/HTLV-1/-2 co-infected individuals, and CCR5-∆32 showed predictive value for ART initiation.


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Williamson SH, Hubisz MJ, Clark AG, Payseur BA, Bustamante CD, et al. Localizing recent adaptive evolution in the human genome. PLoS Genet. 2007;3(6): e90. doi:10.1371/journal.pgen.0030090

O’Bleness M, Searles V, Varki A, Gagneux P, Sikela JM. Evolution of genetic and genomic features unique to the human lineage. Nat Rev Genet. 2012; 13(12):853-66. doi:10.1038/nrg3336

Chatterjee A, Rathore A, Vidyant S, Kakkar K, Dhole TN. Chemokines and chemokine receptors in susceptibility to HIV-1 infection and progression to AIDS. Dis Markers. 2012;32:143-51. doi:10.3233/DMA-2011-0874

Liu R, Paxton WA, Choe S, Ceradini D, Martin SR, Horuk R, et al. Homozygous defect in HIV-1 co-receptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell. 1996;86(3):367-77. doi: 10.1016/S0092-8674(00)80110-5

Barmania F, Pepper MS. C-C chemokine receptor type five (CCR5): An emerging target for the control of HIV infection. Appl Transl Genom. 2013;2:3-16. doi: 10.1016/j.atg.2013.05.004

Winkler C, Modi W, Smith MW, Nelson GW, Wu X, Carrington M, et al. Genetic restriction on AIDS pathogenesis by an SDF-1 chemokine gene variant. Science. 1998; 279(5349):389-93. doi: 10.1126/science.279.5349.389

Thomas DL, Thio CL, Martin MP, Qi Y, Ge D, O’Uigin C, et al. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature. 2009;461:798-801. doi: 10.1038/nature08463

Assone T, Paiva A, Fonseca LAM, Casseb J. Genetic markers of the host in persons living with HTLV-1, HIV and HCV infections. Viruses. 2016;8:38. Available from:

Fang MZ, Jackson SS, Thomas R. O'Brien TR. IFNL4: Notable variants and associated phenotypes. Gene. 2020;730:144289. Available from:

Martinson JJ, Chapman NH, Rees DC, Liu Y-T, Clegg JB. Global distribution of the CCR5 gene 32-basepair deletion. Nat Genet. 1997;16:100-3. doi: 10.1038/ng0597-100

Martinson JJ, Lily H, Karanicolas R, Moore JP, Kostrikis LG. Global distribution of the CCR2-64I/CCR5-59653T HIV-1 disease-protective haplotype. AIDS. 2000;14(5):483-9. doi: 10.1097/00002030-200003310-00003

Su B, Sun G , Lu D, Xiao J, Hu F, Chakraborty R, et al. Distribution of three HIV-1 resistance-conferring polymorphism (SDF1-3’A, CCR2-64I, and CCR5-delta32) in global populations. Eur J Hum Gen. 2000;8:975-9. doi: 10.1038/sj.ejhg.5200568

Mellado M, Rodríguez-Frade JM, Vila-Coro AJ, de Ana AM, C Martínez-A C. Chemokine control of HIV-1 infection. Nature. 1999;400(6746):723-4. doi: 10.1038/23382

Wachira D, Lihana R, Okoth V, Maiyo A, Khamadi SA. Chemokine coreceptor-2 gene polymorphisms among HIV-1 infected individuals in Kenya. Dis Markers. 2015;2015:952067. Available from:

Rafrafi A, Kaabachi S, Kaabachi W, Chahed B, Amor AB, Mbarik M, et al. CCR2-64I polymorphism is associated with non-small cell lung cancer in Tunisian patients. Hum Immunol. 2015; 76(5): 348-4. doi: 10.1016/j.humimm.2015.03.003

Grimaldi R, Acosta AX, Machado TMB, Bomfim TF, Galvão-Castro. Distribution of SDF1-3’A polymorphisms in three different ethnic groups from Brazil. Braz J Infect Dis. 2010;14(2):197-200. doi: 10.1016/S1413-8670(10)70039-8

Cavalcante LN, Abe-Sandes K, Angelo ALD, Machado TMB, Lemaire DC, Mendes CMC, et al. IL28B polymorphisms are markers of therapy response and are influenced by genetic ancestry in chronic hepatitis C patients from an admixed population. Liver Int. 2011; 476-86. doi: 10.1111/j.1478-3231.2011.02653.x

Ramos JA, Ramos ALA, Hoffmann L, Perez RM, Coelho HSM, Ürményi TP, et al. A single nucleotide polymorphism, rs129679860, in the IL28B locus is associated with the viral kinetics and a sustained virological response in a chronic, monoinfected hepatitis C virus genotype-1 Brazilian population treated with pegylated interferon-ribavirin. Mem Inst Oswaldo Cruz, Rio de Janeiro. 2012;107(7):888-92. Available from:

Treviño A, Lopez M, Vispo E, Aguilera A, Ramos JM, Benito R, et al. Development of tropical spastic paraparesis in human T-lymphotropic virus type 1 carriers is influenced by interleukin 28B gene polymorphisms. Clin Infect Dis. 2012;55(1):e1-4. Available from:

Assone T, de Souza FV, Gaester KO, Fonseca LA, Luiz OC, Malta FM, et al. IL28B gene polymorphism SNP rs8099917 genotype GG is associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in HTLV-1 carriers. PLoS Negl Trop Dis. 2014;8(9):e3199. Available from:

Assone T, Malta FM, Bakkour S, Montalvo L, Paiva AM, Smid J, et al. Polymorphisms in HLA-C and KIR alleles are not associated with HAM/TSP risk in HTLV-1-infected subjects. Virus Res. 2018;244:71-4. doi: 10.1016/j.virusres.2017.11.010

de Araújo ESA, Harel Dahari H, Cotler SJ, Layden TJ, Neumann AU, Melo CE, Barone AA. Pharmacodynamics of PEG-IFN alpha-2a and HCV response as a function of IL28B polymorphism in HIV/HCV co-infected patients. J Acquir Immune Defic Syndr. 2011;56(2):95-9. doi: 10.1097/QAI.0b013e3182020596

Ferreira PRA, Santos C, Cortes R, Reis A, Tenore SB, Silva MH, Vilhena C, Diaz RS. Association between IL28B gene polymorphisms and sustained virological response in patients co-infected with HCV and HIV in Brazil. J Antimicrob Chemother. 2012;509-10. doi: 10.1093/jac/dkr488

Caterino-de-Araujo A, Sacchi CT, Gonçalves MG, Campos KR, Magri MC, Alencar WK, et al. Current prevalence and risk factors associated with human T lymphotropic virus type 1 and human T lymphotropic virus type 2 infections among HIV/AIDS patients in São Paulo, Brazil. AIDS Res Hum Retroviruses. 2015;31(5):543-9. doi: 10.1089/AID.2014.0287

Campos KR, Gonçalves MG, Costa NA, Caterino-de-Araujo A. Comparative performances of serologic and molecular assays for detecting human T lymphotropic virus type 1 and type 2 (HTLV-1 and HTLV-2) in patients infected with human immunodeficiency virus type (HIV-1). Braz J Infect Dis. 2017;21(3):297-305. doi: 10.1016/j.bjid.2017.02.005

Campos KR, Caterino-de-Araujo A. Provirus mutations of human T-lymphotropic virus type 1 and type 2 (HTLV-1 and HTLV-2) in HIV-1 co-infected individuals. mSphere. 2020;5(5):e00923-20. Available from:

Gonçalves MG, Fukasawa LO, Campos KR, Higa FT, Caterino-de-Araujo A. Development and validation of multiplex quantitative real-time PCR assays for simultaneous detection and differentiation of HTLV-1 and HTLV-2, using different PCR platforms and reagent brands. Front Microbiol. 2022;13:831594. Available from: 10.3389/fmicb.2022.831594

de Angelis DAS, Freire WS, Cláudio Sergio Pannuti CS, Succi RCM, Machado DM. CCR5 genotypes and progression to HIV disease in perinatally infected children. Braz J Infect Dis. 2007;11(2):196-8. doi: 10.1590/S1413-86702007000200004

Voevodin A, Samilchuk E, Dashti S. Frequencies of SDF-1 chemokine, CCR-5, and CCR-2 chemokine receptor gene alleles conferring resistance to Human Immunodeficiency Virus Type 1 and AIDS in Kuwaitis. J Med Virol. 1999;58:54-8. Available from:;2-N

Moreira S, Garcia RFL, Gutberlet A, Bertol BC, Ferreira LE, Pinho MSL, et al. A straightforward genotyping of the relevant IL28B SNPs for the prediction of hepatitis C treatment outcome. J Virol Methods. 2012;184:93-7. doi: 10.1016/j.jviromet.2012.05.024

Campos KR, Gonçalves MG, Caterino-de-Araujo A. (2017a). Failures in detecting HTLV-1 and HTLV-2 in patients infected with HIV-1. AIDS Res Hum Retroviruses. 2017;33:382-5. doi: 10.1089/AID.2016.0191

Paiva A, Casseb J. Origin and prevalence of human T-lymphotropic virus type 1 (HTLV-1) and type 2 (HTLV-2) among indigenous populations in the Americas. Rev Inst Med Trop Sao Paulo. 2015;57(1):1-13. doi: 10.1590/S0036-46652015000100001

Ministério da Saúde (BR). Secretaria de Vigilância em Saúde, Departamento de Doenças de Condições Crônicas e Infecções Sexualmente Transmissíveis. Guia de manejo clínico da infecção pelo HTLV [Internet]. Brasilia: Ministério da Saúde; 2021 [cited 2022 jun 24]. Available from:

Galvão-Castro B, Grassi MFR, Galvão-Castro AV, Nunes A, Galvão–Barroso AK, Araújo THA, et al. (2022) Integrative and Multidisciplinary Care for People Living With Human T-Cell Lymphotropic Virus in Bahia, Brazil: 20 Years of Experience. Front Med. 2022;9:884127. Available from:

Carvalhaes FAPL, Cardoso GL, Hamoy IG, Liu YT, Guerreiro JF. Distribution of CCR5-[delta]32, CCR2-64I, and SDF1-3’A mutations in populations from the Brazilian Amazon region. Hum Biol. 2004;76(4):643-6. doi: 10.1353/hub.2004.0052.

Carvalhaes FAPL, Cardoso GL, Vallinoto ACR, Machado LF, Ishak MOG, Ishak R et al. Frequencies of CCR5-32, CCR2-64I and SDF1-3’A mutations in human immunodeficiency virus (HIV) seropositive subjects and seronegative individuals from the state of Pará in Brazilian Amazonia. Gen Mol Biol. 2005;28(4):665-9. Available from:

Grimaldi R, Shindo N, Acosta A, Dourado I, Brites C, de Melo Carvalho O, et al. Prevalence of the CCR5Δ32 mutation in Brazilian populations and cell susceptibility to HIV-1 infection. Hum Genet. 2002;111(1):102-4. doi: 10.1007/s00439-002-0747-x

Pereira RW, Pires ER, Duarte APM, de Moura RP, Monteiro E, Torloni H, et al. Frequency of the CCR5∆32 allele in Brazilians: a study in colorectal cancer and in HTLV-I infection. Genet Mol Biol. 2000;23(3):523-6. doi: 10.1590/S1415-47572000000300003

Silva-Carvalho WHV, de Moura RR, Coelho AVC, Crovella S, Guimarães RL. Frequency of the CCR5-delta32 allele in Brazilian populations: A systematic literature review and meta-analysis. Infect Genet Evol. 2016;43:101-7. doi: 10.1016/j.meegid.2016.05.024

Vieira VC, Barral MFM, Mendoza-Sassi RA, Silveira JM, Soares MA, de Martínez AMB. The effect of combined polymorphisms in chemokines and chemokine receptors on the clinical course of HIV-1 infection in a Brazilian population. Mem Inst Oswaldo Cruz, Rio de Janeiro. 2011;106(4):408-14. doi: 10.1590/S0074-02762011000400005

Rigato PO, Hong MA, Casseb J, Ueda M, Castro I, Benard G, et al. Better CD4+ T cell recovery in Brazilian HIV-infected individuals under HAART due to cumulative carriage of SDF-1-3’A, CCR2-V64I, CCR5-D32 and CCR5-promoter 59029A/G polymorphisms. Curr HIV Res. 2008;6(5):466-73. doi: 10.2174/157016208785861131

Beilke MA. Retroviral coinfections: HIV and HTLV: Taking stock of more than a quarter century of research. AIDS Res Hum Retroviruses. 2012;28:139-47. doi: 10.1089/aid.2011.0342

Caterino-de-Araujo A, Campos KR, Oliveira LMS, Rigato PO. Biomarkers in a cohort of HIV-infected patients single- or co-Infected with HTLV-1, HTLV-2, and/or HCV: A cross-sectional, observational study. Viruses. 2022;14:1955. Available from:

Acosta AX, Grimaldi R, Spínola JL, Galvão-Castro B. Distribution of the CCR2-64I allele in three Brazilian ethnic groups. Genet Mol Biol. 2003;26(3):241-43. Available from:

Lima ÉRG, Queiroz MAF, Lima SS, Machado LFA, Cayres-Vallinoto IMV, Vallinoto ACR, et al. CCR5∆32 and SDF13’A: gene variants, expression and influence on biological markers for the clinical progression to AIDS among HIV-1 virus controllers in a mixed population of the Amazon region of Brazil. Int J Mol Sci. 2023;24:4958. Available from:

Treviño A, Lopez M, Vispo E, Aguilera A, Ramos JM, Benito R, et al. Development of tropical spastic paraparesis in human T-lymphotropic virus type 1 carriers is influenced by interleukin 28B gene polymorphisms. Clin Infect Dis. 2012;55(1):e1-4. Available from:

Sanabani SS, Nukui Y, Pereira J, da Costa AC, de Oliveira CS, Pessôa R, et al. Lack of evidence to support the association of a single IL28B genotype SNP rs12979860 with the HTLV-1 clinical outcomes and proviral load. BMC Infect Dis. 2012;12:374 Available from:

Vallinoto ACR, Santana BB, Sá KSG, Ferreira TCS, Sousa CM, Azevedo VN, et al. HTLV-1-associated myelopathy/tropical spastic paraparesis is not associated with SNP rs12979860 of the IL-28B gene. Mediators Inflamm. 2015;2015:804167. Available from:

da Silva Prates G, Malta FM, Toledo F, Monteiro MA, Fonseca LAM, Veiga APR, et al. AIDS incidence and survival in a hospital‐based cohort of HIV‐positive patients from São Paulo, Brazil: The role of IFN‐λ4 polymorphisms. J Med Virol. 2021;93:3601-6. doi: 10.1002/jmv.26054



How to Cite

Caterino-de-Araujo A, Campos KR, Cabral-de-Oliveira EC, Rodrigues AKS, Silva RX, Azevedo BV, Marcusso RMN. CCR5-∆32, CCR2-64I, SDF1-3’A, and IFNλ4 rs12979860 and rs8099917 gene polymorphisms in individuals with HIV-1, HIV/HTLV-1, and HIV/HTLV-2 in São Paulo, Brazil. Microbes Infect. Chemother. [Internet]. 2023 Jun. 5 [cited 2024 Jul. 21];3:e1855. Available from: