Expresión diferencial en placenta de beta-defensinas humanas y detección de variantes alélicas en el gen DEFB1 de madres positivas para VIH-1
Palabras clave:
beta-defensinas, placenta, VIH-1, inmunidad innata, transmisión vertical de enfermedad infecciosa
Resumen
Introducción. Las bajas tasas de infección en neonatos nacidos de madres seropositivas para el VIH-1 resaltan la existencia de mecanismos de defensa natural en la interfase materno-fetal. Las beta-defensinas humanas inhiben la replicación del VIH-1 in vitro y sus polimorfismos están asociados con la resistencia o susceptibilidad al VIH-1.Objetivo. Comparar los niveles de expresión de ARNm de beta-defensinas humanas en placentas de madres seropositivas y en seronegativas para determinar si la infección por VIH-1 induce factores antivirales que pudieran proteger a los bebés de la transmisión del VIH-1.
Materiales y métodos. Los transcritos de HBD-1, 2 y 3 se cuantificaron por PCR en tiempo real y las variantes A692G/G1654A/A1836G del gen DEFB1 se evaluaron por secuenciación.
Resultados. Los niveles de transcritos de HBD-1 fueron significativamente mayores, y los de HBD-3 fueron menores en placentas de madres seropositivas en comparación con los controles. Además, la presencia simultánea de los genotipos A692G A/G y A1836G G/G se asoció con alta expresión de HBD-1 en toda la población estudiada y la variante A692G estuvo en desequilibrio de Hardy-Weinberg en los bebés nacidos de madres seropositivas.
Conclusión. Los resultados contrastantes de los niveles de HBD se deben, probablemente, a estímulos virales y sugieren que el VIH-1 induce una expresión diferencial de beta-defensinas humanas en placenta y que estas proteínas podrían estar involucradas en la protección contra el VIH-1, al menos, en las etapas tempranas del embarazo. Sin embargo, no fue posible asociar estos hallazgos con la protección contra la transmisión vertical del VIH-1, puesto que ninguno de los bebés adquirió la infección.
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2. Ahumada C, González A, Ribadeneira N, Russo M, Villa L. Making the linkages: HIV/AIDS and sexual and reproductive rights. Ottawa: The Youth Coalition; 2006.
3. UNAIDS. WHO. AIDS epidemeic update. Geneva: UNAIDS; 2007.
4. Chouquet C, Burgard M, Richardson S, Rouzioux C, Costagliola D. Timing of mother-to-child HIV-1 transmission and diagnosis of infection based on polymerase chain reaction in the neonatal period by a non-parametric method. AIDS. 1997;11:1183-4.
5. Rouzioux C, Costagliola D, Burgard M, Blanche S, Mayaux M, Griscelli C, et al. Estimated timing of mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission by use of a Markov model. The HIV Infection in Newborns French Collaborative Study Group. Am J Epidemiol. 1995;142:1330-7.
6. The International Perinatal HIV Group. The mode of delivery and the risk of vertical transmission of human immunodeficiency virus type 1, a meta-analysis of 15 prospective cohort studies. N Engl J Med. 1999;340:977-87.
7. Kind C, Rudin C, Siegrist C, Wyler C, Biedermann K, Lauper U, et al. Prevention of vertical HIV transmission: Additive protective effect of elective cesarean section and zidovudine prophylaxis. AIDS. 1998;12:205-10.
8. Lansky A, Jones J, Wan P, Lindegren M, Wortley P. Trends in zidovudine prescription for pregnant women infected with HIV. J Acquir Immune Defic Syndr Hum Retrovirol. 1998;18:289-92.
9. Sperling R, Shapiro D, Coombs R, Todd J, Herman S, McSherry G, et al. Maternal viral load, zidovudine treatment, and the risk of transmission of human immunodeficiency virus type 1 from mother to infant. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med. 1996;335:1621-9.
10. Jovaisas E, Koch MA, Schafer A, Stauber M, Lowenthal D. LAV/HTLV-III in 20-week fetus. Lancet. 1985;2:1129.
11. Lapointe N, Michaud J, Pekovic D, Chausseau JP, Dupuy JM. Transplacental transmission of HTLV-III virus. N Engl J Med. 1985;312:1325-6.
12. Lewis SH, Reynolds-Kohler C, Fox HE, Nelson JA. HIV-1 in trophoblastic and villous Hofbauer cells, and haematological precursors in eight-week fetuses. Lancet. 1990;335:565-8.
13. Mognetti B, Moussa M, Croitoru J, Menu E, Dormont D, Roques P, et al. HIV-1 co-receptor expression on trophoblastic cells from early placentas and permittivity to infection by several HIV-1 primary isolates. Clin Exp Immunol. 2000;119:486-92.
14. Fazeley F, Hu J, Thirkill TL, Douglas GC. Infection of primary human placental fibroblasts with HIV-1, HIV-2, and SIV. Arch Virol. 1997;142:2237-48.
15. Lagaye S, Derrien M, Menu E, Coito C, Tresoldi E, Mauclere P, et al. Cell-to-cell contact results in a selective translocation of maternal human immunodeficiency virus type 1 quasispecies across a trophoblastic barrier by both transcytosis and infection. J Virol. 2001;75:4780-91.
16. Shearer GM, Clerici M. Protective immunity against HIV infection: Has nature done the experiment for us? Immunol Today. 1996;17:21-4.
17. Shacklett BL. Understanding the "lucky few": The conundrum of HIV-exposed, seronegative individuals. Curr HIV/AIDS Rep. 2006;3:26-31.
18. Liu R, Paxton WA, Choe S, Ceradini D, Martin SR, Horuk R, et al. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell. 1996;86:367-77.
19. Samson M, Libert F, Doranz BJ, Rucker J, Liesnard C, Farber CM, et al. Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature. 1996;382:722-5.
20. Buseyne F, Janvier G, Teglas JP, Ivanoff S, Burgard M, Bui E, et al. Impact of heterozygosity for the chemokine receptor CCR5 32-bp-deleted allele on plasma virus load and CD4 T lymphocytes in perinatally human immunodeficiency virus-infected children at 8 years of age. J Infect Dis. 1998;178:1019-23.
21. Marmor M, Sheppard HW, Donnell D, Bozeman S, Celum C, Buchbinder S, et al. Homozygous and heterozygous CCR5-Delta32 genotypes are associated with resistance to HIV infection. J Acquir Immune Defic Syndr. 2001; 27:472-81.
22. Villalba N, Pérez-Olmeda M, de José M, Hernández M, Sirera R, Espanol T, et al. CCR5 genotype and human immunodeficiency virus type 1 infection in perinatally exposed infants. Eur J Clin Microbiol Infect Dis. 1999;18:389-91.
23. Díaz FJ, Vega JA, Patiño PJ, Bedoya G, Nagles J, Villegas C, 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;95:237-42.
24. Rugeles MT, Solano F, Díaz FJ, Bedoya VI, Patiño PJ. Molecular characterization of the CCR 5 gene in seronegative individuals exposed to human immunodeficiency virus (HIV). J Clin Virol. 2002;23:161-9.
25. Huang Y, Paxton W, Wolinsky S, Neumann A, Zhang L, He T, et al. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat Med. 1996;2:1240-3.
26. Edelstein RE, Arcuino LA, Hughes JP, Melvin AJ, Mohan KM, King PD, et al. Risk of mother-to-infant transmission of HIV-1 is not reduced in CCR5/delta32ccr5 heterozygotes. J Acquir Immune Defic Syndr Hum Retrovirol. 1997;16:243-6.
27. Rousseau CM, Just JJ, Abrams EJ, Casabona J, Stein Z, King MC. CCR5del32 in perinatal HIV-1 infection. J Acquir Immune Defic Syndr Hum Retrovirol. 1997;16:239-42.
28. Coulomb-L'Hermine A, Emilie D, Durand-Gasselin I, Galanaud P, Chaouat G. SDF-1 production by placental cells: A potential mechanism of inhibition of mother-to-fetus HIV transmission. AIDS Res Hum Retroviruses. 2000;16:1097-8.
29. Patterson BK, Behbahani H, Kabat WJ, Sullivan Y, O'Gorman MR, Landay A, et al. Leukemia inhibitory factor inhibits HIV-1 replication and is upregulated in placentae from nontransmitting women. J Clin Invest. 2001;107:287-94.
30. Bedoya VI, Jaimes FA, Delgado JC, Rugeles C, Usuga X, Zapata W, et al. Fetal-maternal HLA-A and -B discordance is associated with placental RNase expression and anti-HIV-1 activity. Curr HIV Res. 2008;6:380-7.
31. Lee-Huang S, Huang PL, Sun Y, Kung HF, Blithe DL, Chen HC. Lysozyme and RNases as anti-HIV components in beta-core preparations of human chorionic gonadotropin. Proc Natl Acad Sci USA. 1999;96:2678-81.
32. Bourinbaiar AS, Nagorny R. Inhibitory effect of human chorionic gonadotropin (hCG) on HIV-1 transmission from lymphocytes to trophoblasts. FEBS Lett. 1992;309:82-4.
33. Polliotti BM, Gnall-Sazenski S, Laughlin TS, Miller RK. Inhibitory effects of human chorionic gonadotropin (hCG) preparations on HIV infection of human placenta in vitro. Placenta. 2002;23(Suppl.A):S102-6.
34. King AE, Paltoo A, Kelly RW, Sallenave JM, Bocking AD, Challis JR. Expression of natural antimicrobials by human placenta and fetal membranes. Placenta. 2007;28:161-9.
35. Svinarich DM, Gómez R, Romero R. Detection of human defensins in the placenta. Am J Reprod Immunol. 1997;38:252-5.
36. Zhao C, Wang I, Lehrer RI. Widespread expression of beta-defensin hBD-1 in human secretory glands and epithelial cells. FEBS Lett. 1996;396:319-22.
37. Yang D, Biragyn A, Kwak LW, Oppenheim JJ. Mammalian defensins in immunity: More than just microbicidal. Trends Immunol. 2002;23:291-6.
38. Yang D, Biragyn A, Hoover DM, Lubkowski J, Oppenheim JJ. Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense. Annu Rev Immunol. 2004;22:181-215.
39. Klotman ME, Chang TL. Defensins in innate antiviral immunity. Nat Rev Immunol. 2006;6:447-56.
40. Quinones-Mateu ME, Lederman MM, Feng Z, Chakraborty B, Weber J, Rangel HR, et al. Human epithelial beta-defensins 2 and 3 inhibit HIV-1 replication. AIDS. 2003;17:F39-48.
41. Sun L, Finnegan CM, Kish-Catalone T, Blumenthal R, Garzino-Demo P, La Terra GM, et al. Human beta-defensins suppress human immunodeficiency virus infection: Potential role in mucosal protection. J Virol. 2005;79:14318-29.
42. Zapata W, Rodríguez B, Weber J, Estrada H, Quiñones-Mateu M, Zimermman P, et al. Increased levels of human beta-defensins mRNA in sexually HIV-1 exposed but uninfected individuals. Curr HIV Res. 2008;6:531-8.
43. Jurevic RJ, Chrisman P, Mancl L, Livingston R, Dale BA. Single-nucleotide polymorphisms and haplotype analysis in beta-defensin genes in different ethnic populations. Genet Test. 2002;6:261-9.
44. Braida L, Boniotto M, Pontillo A, Tovo PA, Amoroso A, Crovella S. A single-nucleotide polymorphism in the human beta-defensin 1 gene is associated with HIV-1 infection in Italian children. AIDS. 2004;18:1598-600.
45. Milanese M, Segat L, Pontillo A, Arraes LC, de Lima Filho JL, Crovella S. DEFB1 gene polymorphisms and increased risk of HIV-1 infection in Brazilian children. AIDS. 2006;20:1673-5.
46. Segat L, Milanese M, Boniotto M, Crovella S, Bernardon M, Costantini M, et al. DEFB-1 genetic polymorphism screening in HIV-1 positive pregnant women and their children. J Matern Fetal Neonatal Med. 2006;19:13-6.
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Cómo citar
1.
Aguilar-Jiménez W, Zapata W, Rugeles MT. Expresión diferencial en placenta de beta-defensinas humanas y detección de variantes alélicas en el gen DEFB1 de madres positivas para VIH-1. Biomed. [Internet]. 16 de abril de 2011 [citado 2 de febrero de 2025];31(1):44-5. Disponible en: https://revistabiomedica.org/index.php/biomedica/article/view/335
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