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Prevalence a role CCR5Δ32 v progresi onemocnění u HIV pozitivních pacientů v České republice


Autoři: L. Sácká 1;  J. Hodek 1;  L. Machala 2;  M. Malý 3 ;  J. Weber 1
Působiště autorů: Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic 1;  Department of Infectious Diseases, Third Faculty of Medicine, Charles University and Hospital Na Bulovce, Prague, Czech Republic 2;  National Institute of Public Health, Prague, Czech Republic 3
Vyšlo v časopise: Epidemiol. Mikrobiol. Imunol. 68, 2019, č. 3, s. 138-143
Kategorie: Původní práce

Souhrn

Úvod: Vstup viru lidské imunitní nedostatečnosti typu 1 (HIV-1) do cílových buněk je umožněn CD4 receptorem a jedním ze dvou koreceptorů CXCR4 nebo CCR5. Delece úseku 32 nukleotidů v genu pro CCR5 (CCR5Δ32) v obou alelách poskytuje silnou, avšak ne absolutní odolnost proti infekci HIV-1 a delece v jedné alele zpomaluje postup nemoci směřující k rozvinutí AIDS. Zde jsme analyzovali prevalenci a roli heterozygotního výskytu CCR5Δ32 na postup onemocnění u HIV pozitivních jedinců v České republice.

Metody: Celkem 92 HIV-1 séropozitivních osob včetně 80 Čechů z AIDS centra v Nemocnici Na Bulovce v Praze bylo zařazeno do genotypizace CCR5, která byla součástí studie role HIV fitness na průběh onemocnění. Z periferních mononukleárních buněk pacienta byla získána DNA, která byla použita k amplifikaci pomocí PCR v reálném čase použitím specifických sond, které detekovaly divokou variantu CCR5 a variantu s 32 nt delecí. Podmnožina 74 pacientů bez antiretrovirové léčby, kteří byli sledováni déle než jeden rok, byla použita k určení role heterozygotního fenotypu CCR5 na průběh nemoci.

Výsledky: Heterozygotní CCR5Δ32 varianta byla nalezena u 23,8 % z 80 českých HIV-1 séropozitivních osob, což je velmi podobné jako publikovaná 21 % a 24 % prevalence u HIV negativní české populace. Homozygotní mutovaná varianta nebyla nalezena. U skupiny osob s heterozygotním CCR5 fenotypem jsme pozorovali slabě zvýšený průměrný počet CD4-pozitivních T-lymfocytů a nižší průměrné hodnoty virémie v plazmě.

Závěr: Celkově, naše studie neukázala žádný zřejmý užitek přítomnosti heterozygotní CCR5Δ32 varianty na přenos HIV a pouze malý užitek na průběh nemoci u české HIV-1 pozitivní kohorty.

Klíčová slova:

HIV-1 – koreceptor CCR5 – CCR5Δ32 – heterozygotní polymorfismus – progrese nemoci


Zdroje

1. Agrawal L, Alkhatib G, Agrawal L. Chemokine receptors: emerging opportunities for new anti-HIV therapies. Expert Opin Ther Targets, 2001;5(3):303–326.

2. Berger EA, Murphy PM, Farber JM. Chemokine receptors as HIV-1coreceptors: roles in viral entry, tropism, and disease. Annu Rev Immunol,1999;17 : 657–700.

3. Deng H, Liu R, Ellmeier W, et al. Identification of a major co-receptor for primary isolates of HIV-1. Nature, 1996;381(6584):661–666.

4. Dragic T, Litwin V, Allaway GP, et al. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature, 1996;381(6584):667–673.

5. Feng Y, Broder CC, Kennedy PE, et al. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science, 1996;272(5263):872–877.

6. Barroga CF, Raskino C, Fangon MC, et al. The CCR5Delta32 allele slows disease progression of human immunodeficiency virus-1-infected children receiving antiretroviral treatment. J Infect Dis, 2000;182(2):413–419.

7. de Roda Husman AM, Koot M, Cornelissen M, et al. Association between CCR5 genotype and the clinical course of HIV-1 infection. Ann Intern Med, 1997;127(10):882–890.

8. Dean M, Carrington M, Winkler C, et al. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study. Science, 1996;273(5283):1856–1862.

9. Eugen-Olsen J, Iversen AK, Garred P, et al. Heterozygosity for a deletion in the CKR-5 gene leads to prolonged AIDS-free survival and slower CD4 T-cell decline in a cohort of HIV-seropositive individuals. AIDS, 1997;11(3):305–310.

10. Huang Y, Paxton WA, Wolinsky SM, et al. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat Med, 1996;2(11):1240–1243.

11. Ruiz-Mateos E, Tar ancon-Diez L, Alvarez-Rios AI, et al. Association of heterozygous CCR5Delta32 deletion with survival in HIV-infection: A cohort study. Antiviral Res, 2018;150 : 15–19.

12. Henrich TJ, Hanhauser E, Hu Z, et al. Viremic control and viral coreceptor usage in two HIV-1-infected persons homozygous for CCR5 Delta32. AIDS, 2015;29(8):867–876.

13. Limborska SA, Balanovsky OP, Balanovskaya EV, et al. Analysis of CCR5Delta32 geographic distribution and its correlation with some climatic and geographic factors. Hum Hered, 2002;53(1):49–54.

14. Liu R, Paxton WA, Choe S, et al. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell, 1996;86(3):367–377.

15. Martinson JJ, Chapman NH, Rees DC, et al. Global distribution of the CCR5 gene 32-basepair deletion. Nat Genet, 1997;16(1):100–103.

16. Novembre J, Galvani AP, Slatkin M. The geographic spread of the CCR5 Delta32 HIV-resistance allele. PLoS Biol, 2005;3(11):e339.

17. Su B, Sun G, Lu D, et al. Distribution of three HIV-1 resistance-conferring polymorphisms (SDF1-3’A, CCR2-641, and CCR5-delta32) in global populations. Eur J Hum Genet, 2000;8(12):975–979.

18. Drabek J, Petrek M. 32 bp deletion in CCR-5 gene and human immunodeficiency virus epidemic in the Czech Republic. Acta Virol, 1998;42(2):121–122.

19. Šerý O, Hladilová R, Šimek V, et al. Frequency of CCR5 deletion polymorphisms in the Czech Republic population and its relationship to HIV [in czech]. 11th International workshop on AIDS, drugs and us; 2002; Prague, Czech Republic. p. 18.

20. Sedlacek D. The occurrence of CCR5 del32 and CCR2B alleles in HIV-1 positive persons in the Czech Republic. 14th European Congress of Clinical Microbiology and Infectious Diseases; May 1-4, 2004; Prague, Czech Republic.

21. Wu L, Paxton WA, Kassam N, et al. CCR5 levels and expression pat-tern correlate with infectability by macrophage-tropic HIV-1, in vitro. J Exp Med, 1997;185(9):1681–1691.

22. Kim A, Pettoello-Mantovani M, Goldstein H. Decreased susceptibility of peripheral blood mononuclear cells from individuals heterozygous for a mutant CCR5 allele to HIV infection. J Acquir Immune Defic Syndr Hum Retrovirol, 1998;19(2):145–149.

23. Venkatesan S, Petrovic A, Van Ryk DI, et al. Reduced cell surface expression of CCR5 in CCR5Delta 32 heterozygotes is mediated by gene dosage, rather than by receptor sequestration. J Biol Chem, 2002;277(3):2287–301.

24. Benkirane M, Jin DY, Chun RF, et al. Mechanism of transdominant inhibition of CCR5-mediated HIV-1 infection by ccr5delta32. J Biol Chem, 1997;272(49):30603–30606.

25. Chelli M, Alizon M. Determinants of the trans-dominant negative effect of truncated forms of the CCR5 chemokine receptor. J Biol Chem, 2001;276(50):46975–46982.

26. Agrawal L, Lu X, Qingwen J, et al. Role for CCR5Delta32 protein in resistance to R5, R5X4, and X4 human immunodeficiency virus type 1 in primary CD4+ cells. J Virol, 2004;78(5):2277–2287.

27. Reynes J, Portales P, Segondy M, et al. CD4 T cell surface CCR5 density as a host factor in HIV-1 disease progression. AIDS, 2001;15(13):1627–1634.

28. Reynes J, Portales P, Segondy M, et al. CD4+ T cell surface CCR5 density as a determining factor of virus load in persons infected with human immunodeficiency virus type 1. J Infect Dis, 2000;181(3):927–932.

29. Marmor M, Sheppard HW, Donnell D, et al. Homozygous and heterozygous CCR5-Delta32 genotypes are associated with resistance to HIV infection. J Acquir Immune Defic Syndr, 2001;27(5):472–481.

30. Hoffman TL, MacGregor RR, Burger H, et al. CCR5 genotypes in sexually active couples discordant for human immunodeficiency virus type 1 infection status. J Infect Dis, 1997;176(4):1093–1096.

31. Samson M, Libert F, Doranz BJ, et al. Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature, 1996;382(6593):722–725.

32. Papa A, Papadimitriou E, Adwan G, et al. HIV-1 co-receptor CCR5 and CCR2 mutations among Greeks. FEMS Immunol Med Microbiol, 2000;28(1):87–89.

33. Trecarichi EM, Tumbarello M, de Gaetano Donati K, et al. Partial protective effect of CCR5-Delta 32 heterozygosity in a cohort of heterosexual Italian HIV-1 exposed uninfected individuals. AIDS Res Ther, 2006;3 : 22.

34. Grimaldi R, Shindo N, Acosta AX, et al. Prevalence of the CCR5Delta32 mutation in Brazilian populations and cell susceptibility to HIV-1 infection. Hum Genet, 2002;111(1):102–104.

35. Lockett SF, Alonso A, Wyld R, et al. Effect of chemokine receptor mutations on heterosexual human immunodeficiency virus transmission. J Infect Dis, 1999;180(3):614–621.

36. Zamarchi R, Indraccolo S, Minuzzo S, et al. Frequency of a mutated CCR-5 allele (delta32) among Italian healthy donors and individuals at risk of parenteral HIV infection. AIDS Res Hum Retroviruses, 1999;15(4):337–344.

37. Wang FS, Hong WG, Cao Y, et al. Population survey of CCR5 delta32, CCR5 m303, CCR2b 64I, and SDF1 3’A allele frequencies in indigenous Chinese healthy individuals, and in HIV-1-infected and HIV-1-uninfected individuals in HIV-1 risk groups. J Acquir Immune Defic Syndr, 2003;32(2):124–130.

38. Diaz FJ, Vega JA, Patino PJ, et al. Frequency of CCR5 delta-32 mutation in human immunodeficiency virus (HIV)-seropositive and HIV-exposed seronegative individuals and in general population of Medellin, Colombia. Mem Inst Oswaldo Cruz, 2000;95(2):237–242.

39. Liu S, Kong C, Wu J, et al. Effect of CCR5-Delta32 heterozygosity on HIV-1 susceptibility: a meta-analysis. PLoS One, 2012;7(4):e35020.

40. Magierowska M, Theodorou I, Debre P, et al. Combined genotypes of CCR5, CCR2, SDF1, and HLA genes can predict the long-term nonprogressor status in human immunodeficiency virus-1-infected individuals. Blood, 1999;93(3):936–941.

41. Michael NL, Louie LG, Rohrbaugh AL, et al. The role of CCR5 and CCR2 polymorphisms in HIV-1 transmission and disease progression. Nat Med, 1997;3(10):1160–1162.

42. Mulherin SA, O’Brien TR, Ioannidis JP, et al. Effects of CCR5-Delta32 and CCR2-64I alleles on HIV-1 disease progression: the protection varies with duration of infection. AIDS, 2003;17(3):377–387.

43. Rappaport J, Cho YY, Hendel H, et al. 32 bp CCR-5 gene dele-tion and resistance to fast progression in HIV-1 infected heterozygotes. Lancet, 1997;349(9056):922–923.

44. Ioannidis JP, Rosenberg PS, Goedert JJ, et al. Effects of CCR5-Delta32, CCR2-64I, and SDF-1 3’A alleles on HIV-1 disease progression: An international meta-analysis of individual-patient data. Ann Intern Med, 2001;135(9):782–795.

45. Wasik TJ, Smolen J, Kruszynski P, et al. Effects of CCR5-delta32, CCR2-64I and SDF-1-3’A polymorphic alleles on human immunodeficiency virus 1 (HIV-1) infection in the Polish population. Wiad Lek, 2005;58(9–10):500–507.

46. Jagodzinski PP, Lecybyl R, Ignacak M, et al. Distribution of 32 alelle of the CCR5 gene in the population of Poland. J Hum Genet, 2000;45(5):271–274.

47. Zwolinska K, Knysz B, Rybka K, et al. Protective effect of CCR5-Delta32 against HIV infection by the heterosexual mode of transmis-sion in a Polish population. AIDS Res Hum Retroviruses, 2013;29(1):54–60.

48. Takacova M, Nogova P, Habekova M, et al. Prevalence of a 32 bp deletion in the gene for human immunodeficiency virus 1 co-receptor CCR5 in Slovak population. Acta Virol, 2008;52(4):261–264.

49. Apriatin SA, Rakhmanaliev ER, Nikolaeva IA, et al. Comparison CCR5de132 mutation in the CCR5 gene frequencies in Russians, Tuvinians, and in different groups of HIV-infected individuals. Genetika, 2005;41(11):1559–1562.

50. Kazennova EV, Aarons E, Selimova LM, et al. Comparative analysis of distribution of mutant alleles of the gene coding for the CCR-5 chemokine receptor, among people in Russia, infected and not infected with HIV-1. Vopr Virusol, 1998;43(1):30–32.

51. Poljak M, Tomazic J, Seme K, et al. Prevalence of mutant CCR5 allele in Slovenian HIV-1-infected and non-infected individuals. Acta Virol, 1998;42(1):23–26.

52. Mellors JW, Rinaldo CR, Jr., Gupta P, et al. Prognosis in HIV-1 infection predicted by the quantity of virus in plasma [published erratum appears in Science 1997 Jan 3;275(5296):14]. Science, 1996;272(5265):1167–1170.

53. O’Brien TR, Blattner WA, Waters D, et al. Serum HIV-1 RNA levels and time to development of AIDS in the Multicenter Hemophilia Cohort Study. JAMA, 1996;276(2):105–110.

54. Meyer L, Magierowska M, Hubert JB, et al. Early protective effect of CCR-5 delta 32 heterozygosity on HIV-1 disease progression: relationship with viral load. The SEROCO Study Group. AIDS, 1997;11(11):F73–78.

55. Ryabov GS, Kazennova EV, Bobkova MR, et al. Prevalence of alleles associated with HIV resistance in Russia. Genet Test, 2004;8(1):73–76.

56. Brumme ZL, Henrick BM, Brumme CJ, et al. Short communication. Association of the CCR5delta32 mutation with clinical response and >5-year survival following initiation of first triple antiretroviral regimen. Antivir Ther, 2005;10(7):849–853.

57. Parczewski M, Bander D, Leszczyszyn-Pynka M, et al. Risk of all-cause mortality in HIV infected patients is associated with clinical, immunologic predictors and the CCR5 Delta32 deletion. PLoS One, 2011;6(7):e22215.

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