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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2021.tde-11112021-140139
Document
Author
Full name
Nícollas Nunes Rabelo
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2021
Supervisor
Committee
Figueiredo, Eberval Gadelha (President)
Carmona, Maria Jose Carvalho
Pallos, Débora
Joaquim, Marcos Augusto Stavale
Title in Portuguese
Análise molecular de DNA viral na parede de aneurismas intracranianos rotos e não rotos
Keywords in Portuguese
Aneurisma intracraniano
DNA viral
Hemorragia subaracnóidea
Hemorragias intracranianas
Infecções por herpesvirus
Torque teno vírus
Virologia
Abstract in Portuguese
Introdução: A hemorragia subaracnóidea (HSA) causada por aneurisma intracraniano (AI) pode causar, aproximadamente, 50% de mortalidade entre pacientes na faixa etária laboral. A fraqueza estrutural do vaso arterial e sua ruptura ainda são fenômenos pouco compreendidos. Recentes avanços na detecção de DNA viral e a associação de vírus com doenças vasculares fomenta a hipótese de correlacionar a presença de DNA viral na parede do vaso arterial e o AI. O vírus Torque teno vírus (TTV), recentemente, foi descrito e possui alta prevalência na população mundial. Este vírus causa uma viremia no hospedeiro, associada a diversas infecções em estados de imunossupressão do paciente, como sepse e transplante. Por outro lado, o Pan-Herpes vírus humano (pan-HHV), também é muito prevalente. A presença de vírus pode levar a uma resposta inflamatória crônica silenciosa, consequentemente, fragilizando a parede dos vasos arteriais sistêmicos a longo prazo. Objetivo: Avaliar a presença de DNA viral dos vírus TTV e panHHV em tecidos arteriais de AI rotos e não rotos Método: 401 pacientes foram atendidos na Divisão de Clínica Neurocirúrgica do Hospital das Clínicas da FMUSP. Os pacientes foram divididos em dois grupos: os com aneurismas rotos (244) e os com aneurismas não rotos (177). Os vírus analisados foram pan-HHV e TTV nas amostras de tecido vascular cerebral. Os critérios de inclusão e exclusão foram aplicados para seleção da população do estudo. As amostras foram coletadas após a clipagem microcirúrgica e, em seguida, conservadas e submetidas à extração de DNA e à reação em cadeia da polimerase para TTV e pan-HHV, sendo analisados seus oito subtipos. Resultados: foram analisados 35 casos de pacientes elegíveis em que a coleta do material foi factível, destes 22 (62,8%) eram AIs rotos e 13 (37,2%) AIs não rotos. O gênero feminino representou a maior parte da amostra (n = 29; 82,9%), sendo 18 (81,8%) casos rotos e 11(18,2%) não rotos. Os vírus foram detectados em 16 amostras (46%). O TTV em 15 (43%) casos, sendo 10 (28,6%) rotos e cinco (14,4%) não rotos. Apenas um caso da análise revelou-se positivo para pan-HHV com detecção do Epstein-Barr (3%), sendo este paciente do sexo feminino, aneurisma roto e apresentando múltiplos aneurismas. Os aneurismas múltiplos corresponderam a 14 pacientes (40%) da amostra, sendo sete pacientes igualmente distribuídos entre os grupos roto e não roto. A associação entre presença do vírus e múltiplos aneurismas esteve presente em seis (17,2%, p=0,781) casos não sendo estatisticamente significativo. As associações entre a presença do vírus na parede de AI não roto e de AI roto, não se mostraram estatisticamente significativos (p=0,507). Conclusão: A presença de DNA viral de HHV e TTV na parede de AI, correspondeu a 46% da amostra, sendo estes 68% AI rotos. Este achado sugere que a infecção crônica viral pode desempenhar papel na fisiopatologia da formação de AI como fator de risco, no que se refere à influência da alteração da citoarquitetura do vaso, em razão do processo inflamatório envolvido
Title in English
Molecular analysis of viral DNA in patients with ruptured and unruptured intracranial aneurysms
Keywords in English
Human herpes virus
Intracranial aneurysm
Intracranial hemorrhage
Subarachnoid hemorrhage
Torque teno virus
Viral DNA
Virology
Abstract in English
Introduction: Subarachnoid hemorrhage (SAH) caused by intracranial aneurysm (IA) can cause approximately 50% mortality among patients in the working age group. The mechanism of aneurysm formation, the structural weakness of the vessel, and its rupture remain poorly understood. Recent advances in the detection of viral DNA and the association of viruses with vascular diseases justify studying the hypothesis on the relationship between viral infection and the development of cerebral aneurysmal disease. The Torque teno virus (TTV) has recently been discovered and has a high prevalence in the worldwide population. It promotes a lifelong viremia that is associated with many host infections in cases of immunosuppression. On the other hand, the human pan-Herpesvirus (pan-HHV) is also very prevalent. The presence of pathogens implies a silent chronic inflammatory response and changes in the systemic vessel wall. Objective: This study aims to evaluate the prevalence of viral DNA of TTV and pan-HHV in ruptured and non-ruptured IA arterial tissues. Method: 401 patients were admitted in the Neurosurgery Department of Hospital das Clinicas FMUSP at Instituto Central. The patients were divided into two groups: those with ruptured aneurysm (244) and those with non-ruptured aneurysm (177). The viruses analyzed were pan-HHV and TTV in samples of aneurism wall. Inclusion and exclusion criteria were applied. In the operating room, the samples were collected after microsurgical clipping. They were properly preserved and subjected to DNA extraction and polymerase chain reaction for TTV and pan-HHV (eight sub-types were analyzed). Results: Thirty-five cases were eligible, of which 22 (62.8%) were ruptured aneurysms, and 13 (37.2%) were non-ruptured aneurysms. The female gender represented most of the sample (n = 29; 82.9%), with 18 (81.8%) ruptured cases and 11 (18.2%) nonruptured aneurysms. The virus was detected in 16 samples (46%). TTV was detected in 15 (43%) cases, 10 (28,6%) of which were ruptured and five (14,4%) were non-ruptured. Only one case of pan-HHV analysis was positive with the EpsteinBarr virus (3%). This female patient had a ruptured aneurysm and multiple aneurysms. Multiple aneurysms accounted for 14 (40%) cases, with seven patients equally distributed between the ruptured and non-ruptured groups. The association between the presence of the virus and multiple aneurysms was present in six (17.2%, p = 0.781) cases and was not statistically significant. The associations between the presence of the virus on the unruptured IA wall and the ruptured IA was not statistically significant (p = 0.507). Conclusion: The TTV and HHV DNA in the wall of IA, represent 46% of the sample, and 68% of ruptured IA. This finding suggests that infection may play a role in the pathophysiology of IA as a risk factor, regarding the influence of the virus on the inflammatory process
 
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Publishing Date
2021-11-11
 
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