Imunossenescência precoce na infecção por HIV: efeito da persistência viral crônica ou da terapia antirretroviral?

Autores

DOI:

https://doi.org/10.33448/rsd-v9i9.7436

Palavras-chave:

Imunossenescência; HIV; Envelhecimento; Terapia antirretroviral de alta atividade.

Resumo

As terapias antirretrovirais proporcionaram aumento da expectativa de vida das pessoas vivendo com HIV, entretanto uma grande preocupação é o aumento de comorbidades, como doenças cardiovasculares, metabólicas, ósseas e neurodegenerativas, as quais são resultantes de um fenômeno de imunossensibilidade associado ao envelhecimento celular do sistema imunológico, denominado imunossenescência. Este artigo tem como objetivo analisar os principais fatores promotores desse evento na infecção por HIV, discutindo se é resultado de persistência viral crônica ou de terapia antirretroviral. Trata-se de uma revisão da literatura desenvolvida a partir de consulta a Biblioteca Virtual em Saúde, utilizando os bancos de dados MEDLINE e LILACS. Os resultados mostraram que o vírus HIV tem o potencial de influenciar na senescência das células do sistema imunológico pela redução no número de linfócitos T CD4+, aumento de células T CD8+, encurtamento dos telômeros e baixa taxa de renovação pela deficiência na produção de seus precursores. Além disso, o tratamento com antirretrovirais também tem capacidade de acelerar a senescência das células do sistema imune, seja pela ação dos NRTIs sobre a enzima telomerase ou sobre a polimerase das mitocôndrias ou ainda produzindo estresse oxidativo. Portanto, as evidências sugerem que ambos os processos podem contribuir para o estabelecimento acelerado de um fenótipo inflamatório crônico de baixo grau resultando em uma remodelação imune precoce significativa na infecção por HIV.

Referências

Alejos, B., Stella-Ascariz, N., Montejano, R., Rodriguez-Centeno, J., Schwimmer, C., Bernardino, J. I., Rodes, B., Esser, S., Goujard, C., Sarmento-Castro, R., De Miguel, R., Esteban-Cantos, A., Wallet, C., Raffi, F., Arribas, J. R., & NEAT 001/ANRS 143 Study Group (2019). Determinants of blood telomere length in antiretroviral treatment-naïve HIV-positive participants enrolled in the NEAT 001/ANRS 143 clinical trial. HIV medicine, 20(10), 691–698. https://doi.org/10.1111/hiv.12791

Appay, V., & Sauce, D. (2017). Assessing immune aging in HIV-infected patients. Virulence, 8(5), 529–538. https://doi.org/10.1080/21505594.2016.1195536

Bauer, M. E., Wieck, A., Petersen, L. E., & Baptista, T. S. (2015). Neuroendocrine and viral correlates of premature immunosenescence. Annals of the New York Academy of Sciences, 1351, 11–21. https://doi.org/10.1111/nyas.12786

Bektas, A., Schurman, S. H., Sen, R., & Ferrucci, L. (2017). Human T cell immunosenescence and inflammation in aging. Journal of leukocyte biology, 102(4), 977–988. https://doi.org/10.1189/jlb.3RI0716-335

Bellon, M., & Nicot, C. (2017). Telomere Dynamics in Immune Senescence and Exhaustion Triggered by Chronic Viral Infection. Viruses, 9(10), 289. https://doi.org/10.3390/v9100289

Buggert, M., Japp, A. S., & Betts, M. R. (2019). Everything in its right place: resident memory CD8+ T cell immunosurveillance of HIV infection. Current opinion in HIV and AIDS, 14(2), 93–99. https://doi.org/10.1097/COH.0000000000000523

Côté, H. C., Soudeyns, H., Thorne, A., Alimenti, A., Lamarre, V., Maan, E. J., Sattha, B., Singer, J., Lapointe, N., Money, D. M., Forbes, J., CIHR Emerging Team in HIV therapy, aging (CARMA), Wong, J., Bitnun, A., Samson, L., Brophy, J., Burdge, D., Pick, N., van Schalkwyk, J., Montaner, J., … Janssen, P. (2012). Leukocyte telomere length in HIV-infected and HIV-exposed uninfected children: shorter telomeres with uncontrolled HIV viremia. PloS one, 7(7), e39266. https://doi.org/10.1371/journal.pone.0039266

Deeks S. G. (2011). HIV infection, inflammation, immunosenescence, and aging. Annual review of medicine, 62, 141–155. https://doi.org/10.1146/annurev-med-042909-093756

Deeks, S. G., Overbaugh, J., Phillips, A., & Buchbinder, S. (2015). HIV infection. Nature reviews. Disease primers, 1, 15035. https://doi.org/10.1038/nrdp.2015.35

Desai, S., & Landay, A. (2010). Early immune senescence in HIV disease. Current HIV/AIDS reports, 7(1), 4–10. https://doi.org/10.1007/s11904-009-0038-4

Effros R. B. (2016). The silent war of CMV in aging and HIV infection. Mechanisms of ageing and development, 158, 46–52. https://doi.org/10.1016/j.mad.2015.09.003

Erlandson, K. M., Allshouse, A. A., Jankowski, C. M., Lee, E. J., Rufner, K. M., Palmer, B. E., Wilson, C. C., MaWhinney, S., Kohrt, W. M., & Campbell, T. B. (2013). Association of functional impairment with inflammation and immune activation in HIV type 1-infected adults receiving effective antiretroviral therapy. The Journal of infectious diseases, 208(2), 249–259. https://doi.org/10.1093/infdis/jit147

Fastenackels, S., Sauce, D., Vigouroux, C., Avettand-Fènoël, V., Bastard, J. P., Fellahi, S., Nailler, L., Arezes, E., Rouzioux, C., Warszawski, J., Viard, J. P., Appay, V., & ANRS Co19 COVERTE Study Group (2019). HIV-mediated immune aging in young adults infected perinatally or during childhood. AIDS (London, England), 33(11), 1705–1710. https://doi.org/10.1097/QAD.0000000000002275

Figueirêdo Júnior, E. C., Ribeiro, A. D. ., Cruz , J. H. de A. ., Marques, M. H. V. P. ., Marinho, S. A. ., & Pereira, J. V. . (2020). Epidemiological profile of Aids cases reported in Brazil from 2009 to 2019. Research, Society and Development, 9(9), e302997233. https://doi.org/10.33448/rsd-v9i9.7233

Franzese, O., Barbaccia, M. L., Bonmassar, E., & Graziani, G. (2018). Beneficial and Detrimental Effects of Antiretroviral Therapy on HIV-Associated Immunosenescence. Chemotherapy, 63(2), 64–75. Advance online publication. https://doi.org/10.1159/000487534

Fülöp, T., Herbein, G., Cossarizza, A., Witkowski, J. M., Frost, E., Dupuis, G., Pawelec, G., & Larbi, A. (2017). Cellular Senescence, Immunosenescence and HIV. Interdisciplinary topics in gerontology and geriatrics, 42, 28–46. https://doi.org/10.1159/000448542

Gianesin, K., Noguera-Julian, A., Zanchetta, M., Del Bianco, P., Petrara, M. R., Freguja, R., Rampon, O., Fortuny, C., Camós, M., Mozzo, E., Giaquinto, C., & De Rossi, A. (2016). Premature aging and immune senescence in HIV-infected children. AIDS (London, England), 30(9), 1363–1373. https://doi.org/10.1097/QAD.0000000000001093

Guaraldi, G., Franconi, I., Milic, J., Besutti, G., Pintassilgo, I., Scaglioni, R., Ligabue, G., Riva, N., Raimondi, A., Menozzi, M., Carli, F., Zona, S., Santoro, A., Malagoli, A., Borghi, V., Torricelli, P., Cossarizza, A., & Mussini, C. (2019). Thymus Imaging Detection and Size Is Inversely Associated With Metabolic Syndrome and Frailty in People With HIV. Open forum infectious diseases, 6(10), ofz435. https://doi.org/10.1093/ofid/ofz435

Johnson, A. A., Shokhirev, M. N., & Shoshitaishvili, B. (2019). Revamping the evolutionary theories of aging. Ageing research reviews, 55, 100947. https://doi.org/10.1016/j.arr.2019.100947

Kaplan-Lewis, E., Aberg, J. A., & Lee, M. (2017). Aging with HIV in the ART era. Seminars in diagnostic pathology, 34(4), 384–397. https://doi.org/10.1053/j.semdp.2017.04.002

Law, K. M., Satija, N., Esposito, A. M., & Chen, B. K. (2016). Cell-to-Cell Spread of HIV and Viral Pathogenesis. Advances in virus research, 95, 43–85. https://doi.org/10.1016/bs.aivir.2016.03.001

Lee, S. A., Sinclair, E., Hatano, H., Hsue, P. Y., Epling, L., Hecht, F. M., Bangsberg, D. R., Martin, J. N., McCune, J. M., Deeks, S. G., & Hunt, P. W. (2014). Impact of HIV on CD8+ T cell CD57 expression is distinct from that of CMV and aging. PloS one, 9(2), e89444. https://doi.org/10.1371/journal.pone.0089444

Leeansyah, E., Cameron, P. U., Solomon, A., Tennakoon, S., Velayudham, P., Gouillou, M., Spelman, T., Hearps, A., Fairley, C., Smit, d., Pierce, A. B., Armishaw, J., Crowe, S. M., Cooper, D. A., Koelsch, K. K., Liu, J. P., Chuah, J., & Lewin, S. R. (2013). Inhibition of telomerase activity by human immunodeficiency virus (HIV) nucleos(t)ide reverse transcriptase inhibitors: a potential factor contributing to HIV-associated accelerated aging. The Journal of infectious diseases, 207(7), 1157–1165. https://doi.org/10.1093/infdis/jit006

Lori F. (2008). Treating HIV/AIDS by reducing immune system activation: the paradox of immune deficiency and immune hyperactivation. Current opinion in HIV and AIDS, 3(2), 99–103. https://doi.org/10.1097/COH.0b013e3282f525cf

Maeda, K., Das, D., Kobayakawa, T., Tamamura, H., & Takeuchi, H. (2019). Descoberta e desenvolvimento de agentes terapêuticos anti-HIV: progresso em direção a medicamentos para HIV aprimorados. Tópicos atuais em química medicinal , 19 (18), 1621-1649. https://doi.org/10.2174/1568026619666190712204603

McHugh, D., & Gil, J. (2018). Senescence and aging: Causes, consequences, and therapeutic avenues. The Journal of cell biology, 217(1), 65–77. https://doi.org/10.1083/jcb.201708092

Nagai, S., & Azuma, M. (2019). The CD28-B7 Family of Co-signaling Molecules. Advances in experimental medicine and biology, 1189, 25–51. https://doi.org/10.1007/978-981-32-9717-3_2

Nasi, M., De Biasi, S., Gibellini, L., Bianchini, E., Pecorini, S., Bacca, V., Guaraldi, G., Mussini, C., Pinti, M., & Cossarizza, A. (2017). Ageing and inflammation in patients with HIV infection. Clinical and experimental immunology, 187(1), 44–52. https://doi.org/10.1111/cei.12814

Nguyen, V., Mendelsohn, A., & Larrick, J. W. (2017). Interleukin-7 and Immunosenescence. Journal of immunology research, 2017, 4807853. https://doi.org/10.1155/2017/4807853

Paghera, S., Quiros-Roldan, E., Sottini, A., Properzi, M., Castelli, F., & Imberti, L. (2019). Lymphocyte homeostasis is maintained in perinatally HIV-infected patients after three decades of life. Immunity & ageing : I & A, 16, 26. https://doi.org/10.1186/s12979-019-0166-7

Pathai, S., Lawn, S. D., Gilbert, C. E., McGuinness, D., McGlynn, L., Weiss, H. A., Port, J., Christ, T., Barclay, K., Wood, R., Bekker, L. G., & Shiels, P. G. (2013). Accelerated biological ageing in HIV-infected individuals in South Africa: a case-control study. AIDS (London, England), 27(15), 2375–2384. https://doi.org/10.1097/QAD.0b013e328363bf7f

Payne, B. A., Wilson, I. J., Hateley, C. A., Horvath, R., Santibanez-Koref, M., Samuels, D. C., Price, D. A., & Chinnery, P. F. (2011). Mitochondrial aging is accelerated by anti-retroviral therapy through the clonal expansion of mtDNA mutations. Nature genetics, 43(8), 806–810. https://doi.org/10.1038/ng.863

Phetsouphanh, C., Aldridge, D., Marchi, E., Munier, C., Meyerowitz, J., Murray, L., Van Vuuren, C., Goedhals, D., Fidler, S., Kelleher, A., Klenerman, P., & Frater, J. (2019). Maintenance of Functional CD57+ Cytolytic CD4+ T Cells in HIV+ Elite Controllers. Frontiers in immunology, 10, 1844. https://doi.org/10.3389/fimmu.2019.01844

Quiros-Roldan, E., Properzi, M., Paghera, S., Raffetti, E., Castelli, F., & Imberti, L. (2020). Factors associated with immunosenescence during early adulthood in HIV-infected patients after durable efficient combination antiretroviral therapy. Scientific reports, 10(1), 10057. https://doi.org/10.1038/s41598-020-67100-8

Sharp, P. M., & Hahn, B. H. (2011). Origins of HIV and the AIDS pandemic. Cold Spring Harbor perspectives in medicine, 1(1), a006841. https://doi.org/10.1101/cshperspect.a006841

Singh, M. V., Kotla, S., Le, N. T., Ae Ko, K., Heo, K. S., Wang, Y., Fujii, Y., Thi Vu, H., McBeath, E., Thomas, T. N., Jin Gi, Y., Tao, Y., Medina, J. L., Taunton, J., Carson, N., Dogra, V., Doyley, M. M., Tyrell, A., Lu, W., Qiu, X., … Abe, J. I. (2019). Senescent Phenotype Induced by p90RSK-NRF2 Signaling Sensitizes Monocytes and Macrophages to Oxidative Stress in HIV-Positive Individuals. Circulation, 139(9), 1199–1216. https://doi.org/10.1161/CIRCULATIONAHA.118.036232

Smith, R. L., de Boer, R., Brul, S., Budovskaya, Y., & van Spek, H. (2013). Premature and accelerated aging: HIV or HAART?. Frontiers in genetics, 3, 328. https://doi.org/10.3389/fgene.2012.00328

Sokoya, T., Steel, H. C., Nieuwoudt, M., & Rossouw, T. M. (2017). HIV as a Cause of Immune Activation and Immunosenescence. Mediators of inflammation, 2017, 6825493. https://doi.org/10.1155/2017/6825493

Solomon, A., Tennakoon, S., Leeansyah, E., Arribas, J., Hill, A., Van Delft, Y., Moecklinghoff, C., & Lewin, S. R. (2014). No difference in the rate of change in telomere length or telomerase activity in HIV-infected patients after three years of darunavir/ritonavir with and without nucleoside analogues in the MONET trial. PloS one, 9(11), e109718. https://doi.org/10.1371/journal.pone.0109718

Tonet, A. C., & de Tolêdo Nóbrega, O. (2008). Imunossenescência: a relação entre leucócitos, citocinas e doenças crônicas. Revista Brasileira de Geriatria e Gerontologia, 11(2), 259-273.

Tsoukas C. (2014). Immunosenescence and aging in HIV. Current opinion in HIV and AIDS, 9(4), 398–404. https://doi.org/10.1097/COH.0000000000000077

van Marle, G., Church, D. L., van der Meer, F., & Gill, M. J. (2018). Combating the HIV reservoirs. Biotechnology & genetic engineering reviews, 34(1), 76–89. https://doi.org/10.1080/02648725.2018.1471641

Ventura, M. T., Casciaro, M., Gangemi, S., & Buquicchio, R. (2017). Immunosenescence in aging: between immune cells depletion and cytokines up-regulation. Clinical and molecular allergy : CMA, 15, 21. https://doi.org/10.1186/s12948-017-0077-0

Vosgerau, D. S. A. R., & Romanowski, J. P. (2014). Estudos de revisão: implicações conceituais e metodológicas. Revista diálogo educacional, 14(41), 165-189.

Yoshimura K. (2017). Current status of HIV/AIDS in the ART era. Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 23(1), 12–16. https://doi.org/10.1016/j.jiac.2016.10.002

Zhang, H., Puleston, D. J., & Simon, A. K. (2016). Autophagy and Immune Senescence. Trends in molecular medicine, 22(8), 671–686. https://doi.org/10.1016/j.molmed.2016.06.001

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31/08/2020

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MEIRELES, J. V. C. .; BRITO, M. de V. Imunossenescência precoce na infecção por HIV: efeito da persistência viral crônica ou da terapia antirretroviral?. Research, Society and Development, [S. l.], v. 9, n. 9, p. e592997436, 2020. DOI: 10.33448/rsd-v9i9.7436. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/7436. Acesso em: 22 nov. 2024.

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Ciências da Saúde