AGENTES VIRAIS E A PREDISPOSIÇAO PARA DOENÇAS NEOPLASICAS E AUTOIMUNES

(especial para SIIC © Derechos reservados)
Autor:
Janaína luisa Leite
Columnista Experto de SIIC

Institución:
Universidade Estadual de Campinas


Artículos publicados por Janaína luisa Leite
Coautores
Natassia Elena Búfalo* Elaine Cristina Morari** Ana Carolina Trindade Guilhen* Roberto Bernardo Santos* Laura Sterian Ward*** 
Mestre - Pós-graduando, Universidade Estadual de Campinas, Campinas, Brasil*
Doutora - Pesquisadora, Universidade Estadual de Campinas, Campinas, Brasil**
Livre-Docente - Pesquisadora orientadora, Universidade Estadual de Campinas, Campinas, Brasil***
Recepción del artículo
14 de Mayo, 2008
Aprobación
15 de Julio, 2008
Primera edición
26 de Marzo, 2009
Segunda edición, ampliada y corregida
7 de Junio, 2021

Resumen
Os herpesvírus têm sido vistos como potenciais agentes carcinogênicos e identificados em diversas malignidades. Acometem indivíduos imunossuprimidos e também indivíduos saudáveis e possuem elevada prevalência. A capacidade de permanecerem latentes nas células do hospedeiro garante aos vírus sua sobrevivência até serem reativados. Células infectadas por herpes supostamente não seriam destruídas por apoptose em portadores de alterações no gene TP53. Nossos estudos comprovam uma maior prevalência de herpesvírus tipo 6 em pacientes transplantados renais do que numa população controle e mostram que polimorfismos no gene TP53 poderiam influenciar na suscetibilidade à infecção por este vírus. Observamos que os herpesvírus também podem aumentar o risco para o desenvolvimento de carcinomas da pele e isso se associa ao perfil genotípico GSTM1-GSTT1+. Mais recentemente, estudando doenças auto-imunes, observamos que a infecção pelo herpesvírus 6 aumentou a susceptibilidade para o desenvolvimento da doença de Graves. Estes estudos poderão ter utilidade na prevenção de doenças. Por exemplo, pacientes em imunodepressão que tenham infecção por herpesvírus devem ser particularmente mais cuidadosos em relação à exposição solar.

Palabras clave
herpesvírus, câncer, transplantados, tiróide, doença de Graves


Artículo completo

(castellano)
Extensión:  +/-5.43 páginas impresas en papel A4
Exclusivo para suscriptores/assinantes

Abstract
Herpesviruses (HHV) are ubiquitous, have broad tissue tropism and have been found in the thyroid that can be a reservoir of latent HHV. HHV are considered potential carcinogenic agents and have been identified in many malignancies. More recently, they have also been associated to a series of autoimmune conditions. TP53 gene plays a critical role in cell cycle control, facilitating DNA repair activities and protecting against DNA damages. HHV infected cells may gain a dangerous survival time in individuals with impairing apoptotic ability such as the ones caused by TP53 gene polymorphisms. Other genes involved in the response to environmental aggressions, such as the genes that codify the Glutathione S-Transferase (GST) and other enzymatic protective systems, may modulate the risk to develop diseases. We recently demonstrated an increased risk for HHV6 infection in individuals that inherited a codon72TP53 polymorphism which reduces p53 apoptotic activity. Our studies demonstrated a higher prevalence of HHV type 6 in patients submitted to renal transplants than in a control population, suggesting that TP53 gene polymorphisms might affect the susceptibility to HHV infection. In addition, we observed that HHV can increase the risk of skin cancer development, an event associated with the Glutathione S-Transferase (GST) genotypic profile GSTM1-GSTT1+. More recently, investigating autoimmune diseases, we observed a high prevalence of HHV type 7, but not type 6 infection in Graves' disease patients. These individuals also presented the codon72TP53 germline polymorphism more frequently. Although further studies are needed, our results suggest that viral agents such as HHV may trigger autoimmune as well as neoplastic diseases in individuals with a genetic predisposing profile.

Key words
herpesvírus, cancer, predisposition, autoimmune diseases, genetic profile


Clasificación en siicsalud
Artículos originales > Expertos de Iberoamérica >
página   www.siicsalud.com/des/expertocompleto.php/

Especialidades
Principal: Oncología
Relacionadas: Anatomía Patológica, Bioquímica, Diagnóstico por Laboratorio, Endocrinología y Metabolismo, Genética Humana, Infectología, Inmunología, Medicina Interna



Comprar este artículo
Extensión: 5.43 páginas impresas en papel A4

file05.gif (1491 bytes) Artículos seleccionados para su compra



Enviar correspondencia a:
Janaína Luisa Leite, Universidade Estadual de Campinas Faculdade de Ciências Médicas Laboratório de Genética Molecular do Câncer, 13083-970, Campinas, Brasil
Bibliografía del artículo

1. Vineis P. Cancer as an evolutionary process at the cell level: an epidemiological perspective. Carcinogenesis 24:1-6, 2003.
2. Vousden KH, Farrell PJ. Viruses and human cancer. Br Med Bull 50:560-81, 1994.
3. Zur Hausen H. Human genital cancer: synergism between two virus infections or synergism between a virus infection and initiating events? Lancet 18:1370-2, 1982.
4. Schmauz R, Okong P, De Villiers EM, e col. Multiple infections in cases of cervical cancer from a high-incidence area in tropical Africa. Int J Cancer 15:805-9, 1989.
5. Kjaer SK, De Villiers EM, Caglayan H, e col. Human papillomavirus, herpes simplex virus and other potential risk factors for cervical cancer in a high-risk area (Greenland) and a low-risk area (Denmark)--a second look. Br J Cancer 67:830-7, 1993.
6. Frenkel N, Schirmer EC, Wyatt LS e col. Isolation of a new herpesvirus from human CD4+ T cells. Proc Natl Acad Sci USA 87:7797, 1990.
7. Dockrell DH, Smith TF, Paya CV. Human herpesvirus 6. Mayo Clin Proc 74:163-70, 1999.
8. Salahuddin SZ, Ablashi DV, Markham PD e col. Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders. Science 234:596-601, 1986.
9. Stoeckle MY. The spectrum of human herpesvirus 6 infection: from roseola infantum to adult disease. Annu Rev Med 51:423-30, 2000.
10. Levy JA. Three new human herpesviruses (HHV6, 7, and 8). Lancet 349:558-63, 1997.
11. Kosuge H. HHV-6, 7 and their related diseases. J Dermatol Sci 22:205-12, 2000.
12. Berneman ZN, Gallo RC, Ablashi DV e col. Human herpesvirus 7 (HHV-7) strain JI: independent confirmation of HHV-7. J Infect Dis 166:690-1, 1992.
13. Portolani M, Cermelli C, Mirandola P, Di Luca D. Isolation of human herpesvirus 7 from an infant with febrile syndrome. J Med Virol 45:282-3, 1995.
14. Clark DA, Freeland ML, Mackie LK, Jarrett RF, Onions DE. Prevalence of antibody to human herpesvirus 7 by age. J Infect Dis 168:251-2, 1993.
15. Wilborn F, Schmidt CA, Lorenz F e col. Human herpesvirus type 7 in blood donors: detection by the polymerase chain reaction. J Med Virol 47:65-9, 1995.
16. Wyatt LS, Rodriguez WJ, Balachandran N, Frenkel N. Human herpesvirus 7: antigenic properties and prevalence in children and adults. J Virol 65:6260-5, 1991.
17. Black JB, Burns DA, Goldsmith CS e col. Biologic properties of human herpesvirus 7 strain SB. Virus Res 52:25-41, 1997.
18. Lusso P, Secchiero P, Crowley RW, Garzino-Demo A, Berneman ZN, Gallo RC. CD4 is a critical component of the receptor for human herpesvirus 7: interference with human immunodeficiency virus. Proc Natl Acad Sci USA 26:3872-6, 1994.
19. Ablashi DV, Salahuddin SZ, Josephs SF e col. HBLV (or HHV-6) in human cell lines. Nature 329:207, 1987.
20. Berneman ZN, Ablashi DV, Li G e col. Human herpesvirus 7 is a T-lymphotropic virus and is related to, but significantly different from, human herpesvirus 6 and human cytomegalovirus. Proc Natl Acad Sci USA 89:10552-6, 1992.
21. Salahuddin SZ, Ablashi DV, Markham PD e col. Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders. Science 234:596-601, 1986.
22. Gompels UA, Nicholas J, Lawrence G e col. The DNA sequence of human herpesvirus-6: structure, coding content, and genome evolution. Virology 209:29-51, 1995.
23. Osman HK, Peiris JS, Taylor CE, Warwicker P, Jarrett RF, Madeley CR. "Cytomegalovirus disease" in renal allograft recipients: is human herpesvirus 7 a co-factor for disease progression? J Med Virol 48:295-301, 1996.
24. Madhavan HN, Priya K, Bagyalakshmi R. Phenotypic and genotypic methods for the detection of herpes simplex virus serotypes. J Virol Methods 108:97-102, 2003.
25. Rotola A, Gerna G, Di Luca D, Virgili AR, Manservigi R, Cassai E. Herpes simplex virus and human cancer. III. Search for relationship of herpes simplex antibodies and cervical dysplasia and labial neoplasia. Tumori 69:83-7, 1983.
26. Dwyer DE, Cunningham AL. Herpes simplex and varicella-zoster virus infections. Med J Aust 177:267-73, 2002.
27. Abrahams PJ, van der Kleij AA, Schouten R, van der Eb AJ. Absence of induction of enhanced reactivation of herpes simplex virus in cells from xeroderma pigmentosum patients without skin cancer. Cancer Res 48:6054-7, 1988.
28. McGregor JM, Harwood CA, Brooks L e col. Relationship between p53 codon 72 polymorphism and susceptibility to sunburn and skin cancer. J Invest Dermatol 119:84-90, 2002.
29. Osman HK, Peiris JS, Taylor CE, Karlberg JP, Madeley CR. Correlation between the detection of viral DNA by the polymerase chain reaction in peripheral blood leukocytes and serological responses to human herpesvirus 6, human herpesvirus 7, and cytomegalovirus in renal allograft recipients. J Med Virol 53:288-94, 1997.
30. Herbein G, Strasswimmer J, Altieri M, Woehl-Jaegle ML, Wolf P, Obert G. Longitudinal study of human herpesvirus 6 infection in organ transplant recipients. Clin Infect Dis 22:171-3, 1996.
31. DesJardin JA, Gibbons L, Cho E e col. Human herpesvirus 6 reactivation is associated with cytomegalovirus infection and syndromes in kidney transplant recipients at risk for primary cytomegalovirus infection. J Infect Dis 178:1783-6, 1998.
32. Ratnamohan VM, Chapman J, Howse H e col. Cytomegalovirus and human herpesvirus 6 both cause viral disease after renal transplantation. Transplantation 66:877-82, 1998.
33. Dockrell DH, Prada J, Jones MF e col. Seroconversion to human herpesvirus 6 following liver transplantation is a marker of cytomegalovirus disease. J Infect Dis 176:1135-40, 1997.
34. Drobyski WR, Dunne WM, Burd EM e col. Human herpesvirus-6 (HHV-6) infection in allogeneic bone marrow transplant recipients: evidence of a marrow-suppressive role for HHV-6 in vivo. J Infect Dis 167:735-9, 1993.
35. Okuno T, Higashi K, Shiraki K e col. Human herpesvirus 6 infection in renal transplantation. Transplantation 49:519-22, 1990.
36. Humar A, Malkan G, Moussa G, Greig P, Levy G, Mazzulli T. Human herpesvirus-6 is associated with cytomegalovirus reactivation in liver transplant recipients. J Infect Dis 181:1450-3, 2000.
37. Robinson WS. Human herpesvirus 6.Curr Clin Top Infect Dis 14:159-69, 1994.
38. Hall CB. Human herpesviruses at sixes, sevens, and more. Ann Intern Med 127:481-3, 1997.
39. Flamand L, Gosselin J, D'Addario M e col. Human herpesvirus 6 induces interleukin-1 beta and tumor necrosis factor alpha, but not interleukin-6, in peripheral blood mononuclear cell cultures. J Virol 65:5105-10, 1991.
40. Flamand L, Gosselin J, Stefanescu I, Ablashi D, Menezes J. Immunosuppressive effect of human herpesvirus 6 on T-cell functions: suppression of interleukin-2 synthesis and cell proliferation. Blood 86:418, 1995.
41. Butel JS. Viral carcinogenesis: revelation of molecular mechanisms and etiology of human disease. Carcinogenesis 21:405-26, 2000.
42. Leite JL, Manfrinatto JA, Mazzali M, Ward LS. Polymorphisms at exon 4 of p53 and the susceptibility to herpesvirus types 6 and 1 infection in renal transplant recipients. Transpl Int 19:732-7, 2006.
43. Silva AG. Propriedades gerais dos herpesvírus. In: Lupi O, Silva AG, Pereira JR. AC. Herpes: clínica, diagnóstico e tratamento. Rio de Janeiro: Editora MEDSI, pp. 1-13, 2000.
44. Flaitz CM, Hicks MJ. Molecular piracy: the viral link to carcinogenesis. Oral Oncol 34:448-53, 1998.
45. Leite JL, Stolf HO, Reis NA, Ward LS. Human herpesvirus type 6 and type 1 infection increases susceptibility to nonmelanoma skin tumors. Cancer Lett 224:213-9, 2005.
46. Kupryjanczyk J, Bell DA, Yandell DW, Scully RE, Thor AD. p53 expression in ovarian borderline tumors and stage I carcinomas. Am J Clin Pathol 102:671-6, 1994.
47. Chan PK, Ng HK, Hui M, Cheng AF. Prevalence and distribution of human herpesvirus 6 variants A and B in adult human brain. J Med Virol 64:42-6, 2001.
48. Gray A, Guillou L, Zufferey J e col. Persistence of parvovirus B19 DNA in testis of patients with testicular germ cell tumours. J Gen Virol 79:573-9, 1998.
49. Li X, Dumont P, Della Pietra A, Shetler C, Murphy ME. The codon 47 polymorphism in p53 is functionally significant. J Biol Chem 280:24245-51, 2005.
50. Autrup H. Genetic polymorphisms in human xenobiotica metabolizing enzymes as susceptibility factors in toxic response. Mutat Res 464:65-76, 2000.
51. Hayes JD, Pulford DJ. The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol 30:445-600, 1995.
52. Pemble S, Schroeder KR, Spencer SR e col. Human glutathione S-transferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism. Biochem J 300:271-6, 1994.
53. Leite JL, Morari EC, Granja F, Campos GM, Guilhen AC, Ward LS. Influence of the glutathione s-transferase gene polymorphisms on the susceptibility to basal cell skin carcinoma. Rev Med Chil 135:301-6, 2007.
54. Weetman AP, McGregor AM. Autoimmune thyroid disease: developments in our understanding. Endocr Rev 5:309-55, 1984.
55. Caturegli P, Kimura H, Rocchi R, Rose NR. Autoimmune thyroid diseases. Curr Opin Rheumatol 19:44-8, 2007.
56. Hudnall SD. Anatomical mapping of human herpesvirus reservoirs of infection. Mod Pathol 19:726-37, 2006.
57. Mizukawa Y, Shiohara T. Virus-induced immune dysregulation as a triggering factor for the development of drug rashes and autoimmune diseases: with emphasis on EB virus, human herpesvirus 6 and hepatitis C virus. J Dermatol Sci 22:169-80, 2000.
58. Pozo F, Tenorio A. Detection and typing of lymphotropic herpesviruses by multiplex polymerase chain reaction. J Virol Methods 79:9-19, 1999.

 
 
 
 
 
 
 
 
 
 
 
 
Está expresamente prohibida la redistribución y la redifusión de todo o parte de los contenidos de la Sociedad Iberoamericana de Información Científica (SIIC) S.A. sin previo y expreso consentimiento de SIIC.
ua31618
Inicio/Home

Copyright siicsalud © 1997-2024 ISSN siicsalud: 1667-9008