RESUMO
INTRODUCTION: Studies were conducted to investigate changes in the extent of human herpesvirus 8 (HHV-8) shedding and diversity of HHV-8 strains in the mouth of a renal allograft recipient who developed cutaneous post-transplantation Kaposi's sarcoma. METHODS: Matched oral and blood samples were obtained from a Saudi Arabian renal allograft recipient from 3 days before to 38 weeks after transplantation, and from his kidney donor. Polymerase chain reaction (PCR) protocols to amplify selected HHV-8 sub-genomic regions were applied to detect and quantify HHV-8 DNA. Sequence diversity was determined by cloning the PCR products and subjecting them to denaturing gradient gel electrophoresis and to nucleotide sequencing. RESULTS: Before transplantation, the recipient was seropositive for anti-HHV-8 immunoglobulin G, but the donor was seronegative; HHV-8 DNA could be detected in the recipient's blood, whole-mouth saliva (WMS) and buccal exfoliates, and the salivary viral load was estimated as 2.6 million genome-copies/ml. Post-transplantation, the recipient's salivary viral load initially increased to 4.1 million genome-copies/ml, and thereafter declined precipitously, coinciding with an increase in the dosage of valaciclovir given; HHV-8 DNA was detected most often in WMS compared with parotid saliva, and buccal and palatal exfoliates. Carriage of multiple HHV-8 strains was evident in blood and oral samples; whereas before transplantation strains belonging to genotypes A1 and A5 were observed, after transplantation genotype A5 strains became dominant and A2 strains emerged. CONCLUSION: Immunosuppression and antiviral prophylaxis may interact to influence the spectrum of oral HHV-8 strains and the extent of post-transplantation HHV-8 shedding into the mouth.
Assuntos
DNA Viral/genética , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/fisiologia , Terapia de Imunossupressão/efeitos adversos , Transplante de Rim/imunologia , Saliva/virologia , Sarcoma de Kaposi/virologia , Aciclovir/análogos & derivados , Aciclovir/uso terapêutico , Adulto , Antivirais/uso terapêutico , Sangue/virologia , Neoplasias do Colo/sangue , Neoplasias do Colo/etiologia , Neoplasias do Colo/virologia , DNA Viral/análise , Variação Genética , Humanos , Imunofenotipagem , Leucócitos/virologia , Masculino , Dados de Sequência Molecular , Mucosa Bucal/virologia , Sarcoma de Kaposi/sangue , Sarcoma de Kaposi/etiologia , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/virologia , Neoplasias Gástricas/sangue , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/virologia , Valaciclovir , Valina/análogos & derivados , Valina/uso terapêutico , Carga Viral , Eliminação de Partículas ViraisRESUMO
Renal allograft recipients in the Middle East are at high risk of developing Kaposi's sarcoma. This report describes the extent of oral human herpesvirus 8 shedding and the genomic diversity of the virus in five Saudi Arabian kidney transplantation patients in whom Kaposi's sarcoma had developed. PCR protocols were applied to amplify three fragments of the viral genome from whole-mouth saliva, parotid saliva, buccal and palatal exfoliates, plasma, peripheral blood leukocytes and biopsy of the Kaposi's sarcoma lesion, and to quantify the viral load in whole-mouth saliva. Viral DNA was detected in all plasma and biopsy samples, 80% of whole-mouth saliva, 20% of each of the other oral samples, and none of the leukocyte samples. The viral load in the cell-free fraction of whole-mouth saliva ranged between approximately 1.2 x 10(3) and 2.2 x 10(6) genome-copies/ml. Genotypically distinct viral strains were evident: intra-lesionally in 1 patient; intra-orally in one patient; between an oral sample and biopsy in two patients; and in four patients, between an oral sample and plasma, and between plasma and biopsy. Thus, in the patients studied, salivary shedding of human herpesvirus 8 was frequent and could be extensive, and they were prone to multiple infections. Measures to curtail salivary viral transmission to pre- and post-transplantation patients might reduce the incidence of post-transplantation Kaposi's sarcoma.