Mecanismos de resistencia natural al VIH en seres humanos: un resumen de 10 años de investigación en población colombiana
Palabras clave:
VIH, síndrome de inmunodeficiencia adquirida, control de infecciones, antígenos HLA, receptores CCR5, células asesinas naturales, apoptosis, defensinas
Resumen
La historia natural de la infección por el virus de la inmunodeficiencia humana de tipo 1 (VIH-1) es un proceso variable y complejo que, en forma similar a otras infecciones, ha hecho evidente la existencia de mecanismos de resistencia natural que pueden inhibir el establecimiento de la infección o su progresión hacia estadios avanzados. Cuando hay una exposición continua a partículas virales infecciosas, varios mecanismos genéticos e inmunitarios son esenciales para que se establezca la resistencia.
El objetivo de este manuscrito fue revisar todos los mecanismos de resistencia al VIH-1, hasta el momento propuestos en seres humanos, y presentar los resultados más importantes que se han obtenido en diferentes estudios realizados en los últimos 10 años de investigación en esta área, en individuos colombianos, particularmente enfocados en determinar los mecanismos involucrados en la protección de un grupo de personas que se han expuesto repetidamente al virus, pero que han permanecido sin evidencia clínica ni serológica de infección por el VIH-1.
Aunque los estudios llevados a cabo por nuestro grupo de investigación han corroborado el papel protector de algunos de los mecanismos de protección previamente propuestos, la investigación actual en esta área, a nivel mundial, ha hecho evidente que el fenómeno de resistencia natural depende de múltiples factores con una gran influencia genética, y que sólo mediante estudios multicéntricos que involucren individuos con diferente componente genético, podrán establecerse los mecanismos universales de protección. Profundizar en el conocimiento en esta área permitirá el desarrollo de nuevas medidas preventivas y terapéuticas para la infección por el VIH-1.
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2. Summers T. Public policy for health care workers infected with the human immunodeficiency virus. JAMA. 2001;285:882.
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4. Mann JM, Tarantola DJ. HIV 1998: The global picture. Sci Am. 1998;279:82-3.
5. Kedzierska K, Crowe SM. The role of monocytes and macrophages in the pathogenesis of HIV-1 infection. Curr Med Chem. 2002;9:1893-903.
6. MacDougall TH, Shattock RJ, Madsen C, Chain BM, Katz DR. Regulation of primary HIV-1 isolate replication in dendritic cells. Clin Exp Immunol. 2002;127:66-71.
7. Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, et al. Identification of a major co-receptor for primary isolates of HIV-1. Nature. 1996;381:661-6.
8. Dragic T, Litwin V, Allaway GP, Martin SR, Huang Y, Nagashima KA, et al. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature. 1996;381:667-73.
9. Kwon DS, Gregorio G, Bitton N, Hendrickson WA, Littman DR. DC-SIGN-mediated internalization of HIV is required for trans-enhancement of T cell infection. Immunity. 2002;16:135-44.
10. Lambert AA, Gilbert C, Richard M, Beaulieu AD, Tremblay MJ. The C-type lectin surface receptor DCIR acts as a new attachment factor for HIV-1 in dendritic cells and contributes to trans- and cis-infection pathways. Blood. 2008;112:1299-307.
11. Trujillo JR, Rogers R, Molina RM, Dangond F, McLane MF, Essex M, et al. Noninfectious entry of HIV-1 into peripheral and brain macrophages mediated by the mannose receptor. Proc Natl Acad Sci USA. 2007;104:5097-102.
12. Li Q, Estes JD, Schlievert PM, Duan L, Brosnahan AJ, Southern PJ, et al. Glycerol monolaurate prevents mucosal SIV transmission. Nature. 2009;458:1034-8.
13. Buchbinder SP, Katz MH, Hessol NA, O'Malley PM, Holmberg SD. Long-term HIV-1 infection without immunologic progression. AIDS. 1994;8:1123-8.
14. Cao Y, Qin L, Zhang L, Safrit J, Ho DD. Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. N Engl J Med. 1995;332:201-8.
15. Paxton WA, Martin SR, Tse D, O'Brien TR, Skurnick J, VanDevanter NL, et al. Relative resistance to HIV-1 infection of CD4 lymphocytes from persons who remain uninfected despite multiple high-risk sexual exposure. Nat Med. 1996;2:412-7.
16. Goh WC, Markee J, Akridge RE, Meldorf M, Musey L, Karchmer T, et al. Protection against human immunodeficiency virus type 1 infection in persons with repeated exposure: evidence for T cell immunity in the absence of inherited CCR5 coreceptor defects. J Infect Dis. 1999;179:548-57.
17. Stranford SA, Skurnick J, Louria D, Osmond D, Chang SY, Sninsky J, et al. Lack of infection in HIV-exposed individuals is associated with a strong CD8(+) cell noncytotoxic anti-HIV response. Proc Natl Acad Sci USA. 1999;96:1030-5.
18. 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.
19. 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.
20. Huang Y, Paxton WA, Wolinsky SM, Neumann AU, 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.
21. Rugeles MT, Solano F, Díaz FJ, Bedoya VI, Patino PJ. Molecular characterization of the CCR 5 gene in seronegative individuals exposed to human immunodeficiency virus (HIV). J Clin Virol. 2002;23:161-9.
22. Smith MW, Dean M, Carrington M, Winkler C, Huttley GA, Lomb DA, et al. Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE Study. Science. 1997;277:959-65.
23. Winkler C, Modi W, Smith MW, Nelson GW, Wu X, Carrington M, et al. Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. ALIVE Study, Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC). Science. 1998;279:389-93.
24. MacDonald KS, Fowke KR, Kimani J, Dunand VA, Nagelkerke NJ, Ball TB, et al. Influence of HLA supertypes on susceptibility and resistance to human immunodeficiency virus type 1 infection. J Infect Dis. 2000;181:1581-9.
25. Mikhail M, Wang B, Saksena NK. Mechanisms involved in non-progressive HIV disease. AIDS Rev. 2003;5:230-44.
26. Hildeman D, Jorgensen T, Kappler J, Marrack P. Apoptosis and the homeostatic control of immune responses. Curr Opin Immunol. 2007;19:516-21.
27. Rojas M, Barrera LF, Puzo G, García LF. Differential induction of apoptosis by virulent Mycobacterium tuberculosis in resistant and susceptible murine macrophages: role of nitric oxide and mycobacterial products. J Immunol. 1997;159:1352-61.
28. Clem RJ, Fechheimer M, Miller LK. Prevention of apoptosis by a baculovirus gene during infection of insect cells. Science. 1991;254:1388-90.
29. Clouston WM, Kerr JF. Apoptosis, lymphocytotoxicity and the containment of viral infections. Med Hypotheses. 1985;18:399-404.
30. Wallace M, Malkovsky M, Carding SR. Gamma/delta T lymphocytes in viral infections. J Leukoc Biol. 1995;58:277-83.
31. Welsh RM, Lin MY, Lohman BL, Varga SM, Zarozinski CC, Selin LK. Alpha beta and gamma delta T-cell networks and their roles in natural resistance to viral infections. Immunol Rev. 1997;159:79-93.
32. Selin LK, Santolucito PA, Pinto AK, Szomolanyi-Tsuda E, Welsh RM. Innate immunity to viruses: Control of vaccinia virus infection by gamma delta T cells. J Immunol. 2001;166:6784-94.
33. DeVico AL, Gallo RC. Control of HIV-1 infection by soluble factors of the immune response. Nat Rev Microbiol. 2004;2:401-13.
34. Sierra S, Kupfer B, Kaiser R. Basics of the virology of HIV-1 and its replication. J Clin Virol. 2005;34:233-44.
35. Cheng-Mayer C, Liu R, Landau NR, Stamatatos L. Macrophage tropism of human immunodeficiency virus type 1 and utilization of the CC-CKR5 coreceptor. J Virol. 1997;71:1657-61.
36. Gonzalez E, Bamshad M, Sato N, Mummidi S, Dhanda R, Catano G, et al. Race-specific HIV-1 disease-modifying effects associated with CCR5 haplotypes. Proc Natl Acad Sci USA. 1999;96:12004-9.
37. Díaz FJ, Vega JA, Patino 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.
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Cómo citar
1.
Rugeles MT, Velilla PA, Montoya CJ. Mecanismos de resistencia natural al VIH en seres humanos: un resumen de 10 años de investigación en población colombiana. biomedica [Internet]. 7 de marzo de 2011 [citado 18 de abril de 2024];31(2):269-80. Disponible en: https://revistabiomedica.org/index.php/biomedica/article/view/309
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