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Doctoral Thesis
DOI
https://doi.org/10.11606/T.99.2018.tde-26042018-112322
Document
Author
Full name
Paulo Roberto Palma Urbano
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2018
Supervisor
Committee
Romano, Camila Malta (President)
Levi, José Eduardo
Okay, Thelma Suely
Mello, Isabel Maria Vicente Guedes de Carvalho
Pierulivo, Enrique Mario Boccardo
Title in Portuguese
Caracterização do Poliomavirus associado a Tricodisplasia Spinulosa em indivíduos imunocompetentes e imunodeprimidos
Keywords in Portuguese
Dermatologia
Hospedeiro imunocomprometido
Polyomavirus
Abstract in Portuguese
Trichodysplasia spinulosa (TS) é uma doença proliferativa de pele observada em pacientes imunocomprometidos. Caracteriza-se pela formação de espinhas de queratina conhecidos como espículas, acantose epidérmica, dilatação do folículo piloso, queratose actínica, queda dos pelos, pápulas foliculares e, que normalmente, se manifestam na região facial do paciente e extremidades do corpo (constantemente confundida com danos por exposição prolongada ao sol). A TS resulta da infecção ativa com o poliomavírus TSassociado (TSPyV), onde observa-se alta carga viral, expressão de proteína do vírus e formação de partículas. Este estudo desenvolveu métodos moleculares de detecção e sequenciamento do genoma total e parcial de TSPyV e utilizou-se destes métodos para determinar padrões de excreção e viremia em indivíduos imunocompromentidos e imunocompetentes, bem como explorar possíveis vias de transmissão. Ainda, características genéticas e filogenéticas do TSPyV também foram determinadas. Apesar de observamos alta taxa de excreção urinaria em indivíduos imunocomprometidos (57,7%), o vírus não foi encontrado em amostras de água do meio ambiente. Ainda em termos de excreção urinária do TSPyV, apenas 1,4% dos indivíduos imunocompetentes apresentaram virúria (diferente do que se observa para os poliomavirus JCPyV e BKPyV), mas o vírus foi encontrado em leite materno, sugerindo assim a possibilidade de haver transmissão vertical do TSPyV. As análises filogenéticas revelaram a existência de 2 linhagens de vírus circulantes em nosso meio, com características distintas dos já descritos na literatura. As diferenças observadas foram suficientes para que os vírus sejam caracterizados como novos genótipos circulantes de TSPyV.
Title in English
Characterization of Polyomavirus associated with Spinulosa tricodysplasia in immunocompetent and immunocompromised individuals
Keywords in English
Dermatology
Immunocompromised host
Polyomavirus
Abstract in English
Trichodysplasia spinulosa (TS) is a proliferative skin disease seen in immunocompromised patients. It is characterized by the formation of keratin spines known as spicules, epidermal acanthosis, hair follicle dilatation, actinic keratosis, hair loss, follicular papules and, which usually manifest in the facial region and extremities of the body (constantly confounded with damage from prolonged exposure to the sun). TS results from active infection with TS-associated polyomavirus (TSPyV), where high viral load, virus protein expression and particle formation are observed. This study developed molecular methods for detection and sequencing the total and partial genome of TSPyV and, employing these methods, determined patterns of excretion and viremia in immunocompromised and immunocompetent individuals, as well as explored possible transmission pathways. Genetic and phylogenetic characteristics were also determined. Although we observed high rate of urinary shedding in immunocompromised individuals (57.7%), the virus was not found in environmental water samples. Also in terms of urinary excretion of TSPyV, only 1.4% of immunocompetent individuals presented viruria (different from what is observed for polyomaviruses JCPyV and BKPyV), but the virus was found in breast milk, thus suggesting the possibility of vertical transmission. Phylogenetic analyzes revealed the existence of 2 circulating virus strains in our country, with different characteristics from those already described in the literature. The differences seem to be sufficient to characterize the viruses as new genotypes of TSPyV.
 
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Publishing Date
2018-05-28
 
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