A neuropatogenia do vírus da imunodeficiência humana

Araújo, Abelardo de Q-C; Araújo, Alexandra Prufer Q-C; Novis, Sérgio A. Pereira

doi:10.1590/S0004-282X1996000200027

Resumos

A disseminação da infecção pelo vírus da imunodeficiência humana (HIV) e o rápido evolver dos conhecimentos científicos a seu respeito, obrigam os médicos em geral - e os especialistas mais diretamente envolvidos com pacientes infectados - a se atualizarem constantemente. Diversas são as manifestações neurológicas causadas pelo HIV. Variados também são os mecanismos patogênicos atuantes nestas condições, a saber: imunodeficiência, auto-imunidade, efeitos diretos sobre o sistema nervoso, e efeitos tóxicos e metabólicos. As infecções oportunistas decorrem da imunodeficiência causada pela ação do vírus sobre células T CD4+ e células da linhagem monocítico-macrofágica. Polirradiculoneuropatias desmielinizantes e quadros similares à polimiosite idiopática em geral relacionam-se a mecanismos auto-imunes envolvendo provavelmente a aloestimulação inespecífica de células T por proteínas virais. A ação primária do vírus provoca quadros de meningite asséptica, disfunção cognitiva, demência, mielopatia vacuolar e polineuropatias sensitivas, provavelmente através da liberação de produtos neurotóxicos por macrófagos infectados. Drogas anti-retrovirais e outras adjuvantes no tratamento da SIDA podem, por sua vez, ser neurotóxicas. A maior compreensão dos reais mecanismos neuropatogênicos envolvidos na infecção pelo HIV permitirá, no futuro, a utilização de novas, e mais específicas, opções terapêuticas, possibilitando, assim, um controle maior, e mais precoce, das complicações neurológicas desta infecção retroviral.

vírus da imunodeficiência humana; neuropatogenia; auto-imunidade; demência; polineuropatia

The spreading of human immunodeficiency virus (HIV) infection and its increasing scientific knowledge keep the medical staff involved with these patients in permanent need of updating themselves. The different neurologic manifestations caused by HIV are related to a variety of pathogenic mechanisms, as follows: immunodeficiency, autoimmunity, direct effects of the virus on the nervous system, and toxic and metabolic effects. The opportunistic infections are caused by the immunodeficiency due to the action of the virus on CD4+ T cells and on cells of the monocytic-macrophage lineage. Demyelinating polyradiculoneuropathy and polymyositis-like syndromes are related to autoimmune mechanisms involving, probably, the non-specific stimulation of T cells by viral proteins. The primary action of the virus on the nervous system brings out aseptic meningitis, cognitive dysfunction, dementia, vacuolar myelopathy and sensory polyneuropathy probably through liberation of neurotoxic products by the infected macrophages. Antiretroviral drugs and others used to treat patients with AIDS may also have neurotoxic effects. The better understanding of the neuropathogenesis of HIV infection will permit the use of new, and more specific, therapeutical options in the future as well as a more precocious control of its neurologic complications.

human immunodeficiency virus; neuropathogenesis; auto-immunity; dementia; polyneuropathy

A neuropatogenia do vírus da imunodeficiência humana

Neuropathogenesis of HIV infection

Abelardo de Q-C Araújo^I; Alexandra Prufer Q-C Araújo^II; Sérgio A. Pereira Novis^III

^IProfessor Adjunto de Neurologia

^IIProfessora Assistente de Neuropediatria

^IIIProfessor Titular de Neurologia

RESUMO

A disseminação da infecção pelo vírus da imunodeficiência humana (HIV) e o rápido evolver dos conhecimentos científicos a seu respeito, obrigam os médicos em geral - e os especialistas mais diretamente envolvidos com pacientes infectados - a se atualizarem constantemente. Diversas são as manifestações neurológicas causadas pelo HIV. Variados também são os mecanismos patogênicos atuantes nestas condições, a saber: imunodeficiência, auto-imunidade, efeitos diretos sobre o sistema nervoso, e efeitos tóxicos e metabólicos. As infecções oportunistas decorrem da imunodeficiência causada pela ação do vírus sobre células T CD4+ e células da linhagem monocítico-macrofágica. Polirradiculoneuropatias desmielinizantes e quadros similares à polimiosite idiopática em geral relacionam-se a mecanismos auto-imunes envolvendo provavelmente a aloestimulação inespecífica de células T por proteínas virais. A ação primária do vírus provoca quadros de meningite asséptica, disfunção cognitiva, demência, mielopatia vacuolar e polineuropatias sensitivas, provavelmente através da liberação de produtos neurotóxicos por macrófagos infectados. Drogas anti-retrovirais e outras adjuvantes no tratamento da SIDA podem, por sua vez, ser neurotóxicas. A maior compreensão dos reais mecanismos neuropatogênicos envolvidos na infecção pelo HIV permitirá, no futuro, a utilização de novas, e mais específicas, opções terapêuticas, possibilitando, assim, um controle maior, e mais precoce, das complicações neurológicas desta infecção retroviral.

Palavras-chave: vírus da imunodeficiência humana, neuropatogenia, auto-imunidade, demência, polineuropatia.

ABSTRACT

The spreading of human immunodeficiency virus (HIV) infection and its increasing scientific knowledge keep the medical staff involved with these patients in permanent need of updating themselves. The different neurologic manifestations caused by HIV are related to a variety of pathogenic mechanisms, as follows: immunodeficiency, autoimmunity, direct effects of the virus on the nervous system, and toxic and metabolic effects. The opportunistic infections are caused by the immunodeficiency due to the action of the virus on CD4+ T cells and on cells of the monocytic-macrophage lineage. Demyelinating polyradiculoneuropathy and polymyositis-like syndromes are related to autoimmune mechanisms involving, probably, the non-specific stimulation of T cells by viral proteins. The primary action of the virus on the nervous system brings out aseptic meningitis, cognitive dysfunction, dementia, vacuolar myelopathy and sensory polyneuropathy probably through liberation of neurotoxic products by the infected macrophages. Antiretroviral drugs and others used to treat patients with AIDS may also have neurotoxic effects. The better understanding of the neuropathogenesis of HIV infection will permit the use of new, and more specific, therapeutical options in the future as well as a more precocious control of its neurologic complications.

Key words: human immunodeficiency virus, neuropathogenesis, auto-immunity, dementia, polyneuropathy.

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Aceite: 2-fevereiro-1996.

Dr. Abelardo de Queiroz-Campos Araújo - Rua Gildásio Amado 55/s 211 - 22631-020 Rio de Janeiro RJ - Brasil.

Serviço de Neurologia do Hospital Universitário Clemente Fraga Filho e Serviço de Neuropediatria do Institutode Puericultura e Pediatria Martagão Gesteira da Universidade Federal do Rio de Janeiro (UFRJ):

Referências bibliográficas

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2. Atlan H. Gersten MJ. Salk PL. Salk J. Mechanisms of autoimmunity and AIDS: prospects for therapeutic intervention. Res Immunol 1994:145:165-183.
3. Berger JR. Concha M. Progressive multifocal leukoencephalopathy: the evolution of a disease once considered rare. J Neurovirol 1995:1:5-18.
4. Berger JR. Sheremata WA. Resnik L. Multiple sclerosis-like leukoencephalopathy revealing human immunodeficiency virus infection. Neurology 1989:39:324-327.
5. Budka H. Neuropathology of human immunodeficiency virus infection. Brain Pathol 1991; 1:163-175.
6. Cheng-Mayer C, Seto D, Tateno M, Levy JA. Biologic features of HIV-1 that correlate with virulence in the host Science 1988:240:80-82.
7. Chuck SL, Sande MA. Infections with Cryptococcus neoformans in the acquired immunodeficiency syndrome. N Engl J Med 1989:321:794-799.
8. Cinque P. Brytting M. Vago L. Castagna A, Parravicini C, Zanchetta N. Epstein-Barr virus DNA in cerebrospinal fluid from patients with AIDS-related primary lymphoma of the central nervous system. Lancet 1993:342:398-401.
9. Coffin JM. Retroviridae and their replication. In Fields BN, Knipe DN (eds). Virology.Ed2. New York: Raven Press, 1990:1437-1500.
10. Comblath DR. McArthur JC. Predominantly sensory neuropathy in patients with AIDS and AIDS-related complex. Neurology 1988:38:794-796.
11. Dalgleish AG. The immunology of retrovirus disease. In Rudge P (ed). Neurological aspects of human retroviruses. London: Bailliere Tindall, 1992:23-40.
12. Dalgleish AG. The immune response to HIV: potential por immunotherapy? Immunol Today 1995:16:356-358.
13. Dalgleish AG. Beverley PCL. Clapham PR. The CD4 antigen is an essential component of the receptor for the AIDS retrovirus. Nature 1984:312:763-767.
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23. Holland NR. Power C Mathews VP, Glass JD. Form an M, McArthur JC. Cytomegalovirus encephalitis in acquired immunodeficiency syndrome. Neurology 1994:44:507-514.
24. Hollander H, Levy JA. Neurologic abnormalities and recovery of human immunodeficiency virus from cerebrospinal fluid. Ann Intern Med 1987:106:692-695.
25. Huang TE. Chou SM. Occlusive hypertrophic arteritis as the cause of discrete necrosis in CNS toxoplasmosis in the acquired immunodeficiency syndrome. Human Pathol 1988:19:1210-1214.
26. Koga Y, Lindstrom E. Fenyo EM. Wigzell H, Mak TW. High levels of heterodisperse RNAs accumulate in T cells infected with human immunodeficiency virus and in normal thymocytes. Proc Natl Acad Sci USA 1988:85:4521-4525.
27. Lange DJ. Neuromuscular diseases associated with HIV-1 infection. Muscle Nerve 1994;17:16-30.
28. Leonard R, Zagury D. Desportes I, Bernard J, Zagury JF, Gallo RC. Cytopathic effect of HIV in T4 cells is linked to the last stage of virus infection. Proc Natl Acad Sci USA 1988:85:3570-3574.
29. Levy J A. Shimabukuro J. Hollander H. Isolation of AIDS associated retroviruses from cerebrospinal fluid and brain of patients with neurological symptoms. Lancet 19852:586-588.
30. Lifson JD. Feinberg MB. Reyes GR. Induction of CD4 dependent cell fusion by the HTLV-III envelope glycoprotein. Nature 1986323:725-728.
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32. Liu Z-Q, Wood C, Levy J. Cheng-Meyer C. The viral envelope gene is involved in macrophage tropism of a HIV-1 strain isolated from brain tissues. J Virol 1990;64:6148-6153.
33. Luft BJ, Remington JS. Toxoplasmic encephalitis in AIDS. Clin Infect Dis 1992; 15:211-222.
34. Lynn WS, Tweedale A, Cloyd MW. Human immunodeficiency virus (HIV-1) cytotoxicity: perturbation of the cell membrane and depression of phospholipid synthesis. Virology 1987;163:43-51.
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41. Navia BA, Price RW. The acquired immunodeficiency syndrome dementia complex as presenting or sole manifestation of human immunodeficiency virus infection. Arch Neurol 1987;44:65-69.
42. Peluso R, Haase A, Stowring L, Edwards M, Ventura P. A Trojan Horse mechanism for the spread of visna virus in monocytes. Virology 1985;147:231-236.
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47. Pulliam L, Hemdler B, Tanf N. McGrath M. Human immunodeficiency virus-infected macrophages produce soluble factors that cause histological and neurochemical alterations in cultured human brains. J Clin Invest 1991:87:503-512.
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Datas de Publicação

Publicação nesta coleção
06 Dez 2010
Data do Fascículo
Jun 1996

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[1] 1. Araújo AQC. Costa AL. Manifestações nervosas do vírus da imunodeficiência humana. Neurobiol (Recife) 1991:54:81-94.

[2] 2. Atlan H. Gersten MJ. Salk PL. Salk J. Mechanisms of autoimmunity and AIDS: prospects for therapeutic intervention. Res Immunol 1994:145:165-183.

[3] 3. Berger JR. Concha M. Progressive multifocal leukoencephalopathy: the evolution of a disease once considered rare. J Neurovirol 1995:1:5-18.

[4] 4. Berger JR. Sheremata WA. Resnik L. Multiple sclerosis-like leukoencephalopathy revealing human immunodeficiency virus infection. Neurology 1989:39:324-327.

[5] 5. Budka H. Neuropathology of human immunodeficiency virus infection. Brain Pathol 1991; 1:163-175.

[6] 6. Cheng-Mayer C, Seto D, Tateno M, Levy JA. Biologic features of HIV-1 that correlate with virulence in the host Science 1988:240:80-82.

[7] 7. Chuck SL, Sande MA. Infections with Cryptococcus neoformans in the acquired immunodeficiency syndrome. N Engl J Med 1989:321:794-799.

[8] 8. Cinque P. Brytting M. Vago L. Castagna A, Parravicini C, Zanchetta N. Epstein-Barr virus DNA in cerebrospinal fluid from patients with AIDS-related primary lymphoma of the central nervous system. Lancet 1993:342:398-401.

[9] 9. Coffin JM. Retroviridae and their replication. In Fields BN, Knipe DN (eds). Virology.Ed2. New York: Raven Press, 1990:1437-1500.

[10] 10. Comblath DR. McArthur JC. Predominantly sensory neuropathy in patients with AIDS and AIDS-related complex. Neurology 1988:38:794-796.

[11] 11. Dalgleish AG. The immunology of retrovirus disease. In Rudge P (ed). Neurological aspects of human retroviruses. London: Bailliere Tindall, 1992:23-40.

[12] 12. Dalgleish AG. The immune response to HIV: potential por immunotherapy? Immunol Today 1995:16:356-358.

[13] 13. Dalgleish AG. Beverley PCL. Clapham PR. The CD4 antigen is an essential component of the receptor for the AIDS retrovirus. Nature 1984:312:763-767.

[14] 14. Dalgleish AG. Wilson S. Gompels M. Ludlam C, Gazzard B. Coates AM. Habeshaw. J. T-cell receptor variable gene products and early HIV-1 infection. Lancet 1992.339:824-828.

[15] 15. Dreyer EB. Kaiser PK. Offermann JT, Lipton SA. HIV-1 coat protein neurotoxicity prevented by calcium channel antagonists. Science 1990:248:364-367.

[16] 16. Epstein LG, DiCarlo FJ. Joshi VV. Primary lymphoma of the central nervous system in children with acquired immunodeficiency syndrome. Pediatrics 1988:82:355-363.

[17] 17. Epstein LG. Gendelman HE. Human immunodeficiency virus type 1 infection of the nervous system: pathogenetic mechanisms. Ann Neurol 1993:33:429-436.

[18] 18. Falangola MF. Petito CK. Choroid plexus infection in cerebral toxoplasmosis in AIDS patients. Neurology 1993:43:2035-2040.

[19] 19. Griffin JW. Wesselingh S, Oaklander AL. Kunel RW, Griffin DE. MRNA fingerprinting of cytokines and growth (actors: a new means of characterizing nerve biopsies [abstract]. Neurology 1993:43(Suppl. 2):A232.

[20] 20. Guilian D. Vaca K. Noonan CA. Secretion of neurotoxins by mononuclear phagocytes infected with HIV-1. Science 1990250:1593-1596.

[21] 21. Guiloff RJ. Fuller GN. Other neurological diseases in HIV-1 infection: clinical aspects. In: Rudge P.(ed). Neurological aspects of human retroviruses. London: Bailliere Tindall. 1992:175-209.

[22] 22. Guiloff RJ, Tan SV. Central nervous system opportunistic infections in HIV disease: clinical aspects. In Rudge P (ed). Neurological aspects of human retroviruses. London: Bailliere Tindall, 1992:103-154.

[23] 23. Holland NR. Power C Mathews VP, Glass JD. Form an M, McArthur JC. Cytomegalovirus encephalitis in acquired immunodeficiency syndrome. Neurology 1994:44:507-514.

[24] 24. Hollander H, Levy JA. Neurologic abnormalities and recovery of human immunodeficiency virus from cerebrospinal fluid. Ann Intern Med 1987:106:692-695.

[25] 25. Huang TE. Chou SM. Occlusive hypertrophic arteritis as the cause of discrete necrosis in CNS toxoplasmosis in the acquired immunodeficiency syndrome. Human Pathol 1988:19:1210-1214.

[26] 26. Koga Y, Lindstrom E. Fenyo EM. Wigzell H, Mak TW. High levels of heterodisperse RNAs accumulate in T cells infected with human immunodeficiency virus and in normal thymocytes. Proc Natl Acad Sci USA 1988:85:4521-4525.

[27] 27. Lange DJ. Neuromuscular diseases associated with HIV-1 infection. Muscle Nerve 1994;17:16-30.

[28] 28. Leonard R, Zagury D. Desportes I, Bernard J, Zagury JF, Gallo RC. Cytopathic effect of HIV in T4 cells is linked to the last stage of virus infection. Proc Natl Acad Sci USA 1988:85:3570-3574.

[29] 29. Levy J A. Shimabukuro J. Hollander H. Isolation of AIDS associated retroviruses from cerebrospinal fluid and brain of patients with neurological symptoms. Lancet 19852:586-588.

[30] 30. Lifson JD. Feinberg MB. Reyes GR. Induction of CD4 dependent cell fusion by the HTLV-III envelope glycoprotein. Nature 1986323:725-728.

[31] 31. Lipton SA. Laboratory basis of novel therapeutic strategies to prevent HIV-related neuronal injury. In: Price RW. Perry SW (eds). HIV, AIDS and the brain. New York: Raven Press. 1994:183-202.

[32] 32. Liu Z-Q, Wood C, Levy J. Cheng-Meyer C. The viral envelope gene is involved in macrophage tropism of a HIV-1 strain isolated from brain tissues. J Virol 1990;64:6148-6153.

[33] 33. Luft BJ, Remington JS. Toxoplasmic encephalitis in AIDS. Clin Infect Dis 1992; 15:211-222.

[34] 34. Lynn WS, Tweedale A, Cloyd MW. Human immunodeficiency virus (HIV-1) cytotoxicity: perturbation of the cell membrane and depression of phospholipid synthesis. Virology 1987;163:43-51.

[35] 35. Masliah E, Actum C. Ge N. De Tereza R. Terry R, Wiley C. Spectrum of human immunodeficiency virus-associated neocortical damage. Ann Neurol 1992:32:321-329.

[36] 36. Merrill J. Chen I. HIV-1. macrophages, glial cells, and cytokines in AIDS nervous system disease. FASEB 1991:5:2391 -2397.

[37] 37. Merrill JE. Cytokines and retroviruses. Clin Immunol Immunopathol 1992;64:23-27.

[38] 38. Mcyaard L, Otto SA, Jonker RR, Mijnster MJ, Keet RP, Miedema F. Programmed death of T cells in HIV-1 infection. Science 1992;257:217-219.

[39] 39. Mhiri C, Baudrimont M. Bonne G. Zidovudine myopathy: a distinctive disorder associated with mitochondrial dysfunction. Ann Neurol 1991:29:606-614.

[40] 40. Navia BA, Jordan BD. Price RW. The AIDS dementia complex: I. Clinical features. Ann Neurol 1986; 19:517-524.

[41] 41. Navia BA, Price RW. The acquired immunodeficiency syndrome dementia complex as presenting or sole manifestation of human immunodeficiency virus infection. Arch Neurol 1987;44:65-69.

[42] 42. Peluso R, Haase A, Stowring L, Edwards M, Ventura P. A Trojan Horse mechanism for the spread of visna virus in monocytes. Virology 1985;147:231-236.

[43] 43. Perito CK, Navia BA, Cho ES, Jordan BD, George DC, Price RW. Vacuolar myelopathy pathologically resembling subacute combined degeneration in patients with the acquired immunodeficiency syndrome. N Engl J Med 1985:312:874-879.

[44] 44. Porter SB, Sande MA. Toxoplasmosis of the central nervous system in the acquired immunodeficiency syndrome. N Engl J Med 1992327:1643-1648.

[45] 45. Powderiy WG. Cryptococcal meningitis and AIDS. Clin Infect Dis 1993;17:837-842.

[46] 46. Price RW, Brew BJ, Roke M. Central and peripheral nervous system complications of HIV-1 infection and AIDS. In DeVita VT, Hellman S. Rosenberg SA (eds). AIDS. Philadelphia: J.B. Lippincott, 1992:237-257.

[47] 46a. Puccioni Sohler MP, Coma RB, Perez MA, Schechter M, Ramos C Filho, Novis SAP. Complicações neurológicas na SIDA: experiência do HUCFF/UFRJ. Arq Neuropsiquiatr 1991;49:159-163.

[48] 47. Pulliam L, Hemdler B, Tanf N. McGrath M. Human immunodeficiency virus-infected macrophages produce soluble factors that cause histological and neurochemical alterations in cultured human brains. J Clin Invest 1991:87:503-512.

[49] 48. Pulliam L, Moore D, West DC. Human cytomegalovirus induces IL-6 and TNF-alpha from macrophages and microglial cells: possible role in neurotoxicity. J Neurovirol 1995;t:219-227.

[50] 49. Remick SC. Diamond C, Migliozzi J A. Primary central nervous system lymphoma in patients with and without the acquired immune deficiency syndrome. A retrospective analysis and review of the literature. Medicine 1990;69:345-360.

[51] 50. Resnik L, Berger J, Shapshak P, TourteUotte W. Early penetration of the blood-brain-barrier by HIV. Neurology 1988:38:9-14.

[52] 51. SabatierJ-M, Vives E, Mabrouk K. Evidence for neurotoxic activity of tat from human immunodeficinecy virus type 1.J Virol 1991,65561-967.

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