Cytomegalovirus (CMV) genotype in allogeneic hematopoietic stem cell transplantation

Based on sequence variation in the UL55 gene that encodes glycoprotein B (gB), human cytomegalovirus (CMV) can be classified into four gB genotypes. Previous studies have suggested an association between CMV gB genotype and clinical outcome in patients who underwent an allogeneic hematopoietic stem...

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Published in:	BMC infectious diseases Vol. 13; no. 1; p. 310
Main Authors:	Dieamant, Débora C, Bonon, Sandra H A, Peres, Renata M B, Costa, Claudia R C, Albuquerque, Dúlcinéia M, Miranda, Eliana C M, Aranha, Francisco J P, Oliveira-Duarte, Gislaine, Fernandes, Virginio C A, De Souza, Carmino A, Costa, Sandra C B, Vigorito, Afonso C
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 10-07-2013 BioMed Central
Subjects:	Adolescent Adult Aged Cytomegalovirus Cytomegalovirus - genetics Cytomegalovirus - isolation & purification Cytomegalovirus Infections - virology Cytomegaloviruses DNA, Viral - blood Female Gastrointestinal diseases Genes, Viral Genetic aspects Genotype Genotyping Techniques Graft vs Host Disease Hematopoietic Stem Cell Transplantation Hematopoietic stem cells Homografts Human cytomegalovirus Humans Kaplan-Meier Estimate Male Medical research Medicine, Experimental Middle Aged Molecular Typing Polymerase chain reaction Real-Time Polymerase Chain Reaction Statistics, Nonparametric Stem cells Transplantation Transplantation, Homologous Transplants & implants Viral Envelope Proteins - genetics Viral Load
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Summary:	Based on sequence variation in the UL55 gene that encodes glycoprotein B (gB), human cytomegalovirus (CMV) can be classified into four gB genotypes. Previous studies have suggested an association between CMV gB genotype and clinical outcome in patients who underwent an allogeneic hematopoietic stem cell transplant (HSCT). The goals of this study were identify patients with active infection caused by CMV in recipients of HSCT; determine the prevalence of CMV genotypes in the study group; correlate genotype with CMV disease, acute GVHD and overall survival. The diagnosis of active CMV infection after allogeneic HSCT was detected by antigenemia (AGM) and/or nested-PCR (N-PCR). Positive samples from patients with active CMV infection were submitted to genotyping using N-PCR to amplify a region of UL55, followed by restriction analysis based on HinfI and RsaI digestion. Real-time PCR (qPCR) was used to determine the viral load during active CMV infection and antiviral treatment. Sixty-three allogeneic HSCT recipients were prospectively evaluated; 49/63 (78%) patients were infected with CMV genotypes - gB1 19/49 (39%), gB2 17/49 (35%), gB3 3/49 (6%), gB4 7/49 (14%) - and 3 (6%) had mixed CMV genotypes (gB1 + gB3, gB1 + gB4 and gB2 + gB4). Characterized by gastrointestinal disease, CMV disease occurred in 3/49 (6.1%) patients, who had CMV gB3 genotype. These gB3 genotype patients presented an increasing AGM number, mean 125 (± 250) (P = 0.70), and qPCR copies/ml, mean 37938 (SD ± 50542) (P = 0.03), during antiviral treatment, when compared with other CMV genotypes. According to CMV genotypes, stratified overall survival was 55% for gB1, 43% for gB2; 0% for gB3 and 57% for gB4 (P = 0.03). One of the restrictions of the presented study was the low number of CMV gB sub-cohorts). However, we demonstrated that the frequency of active CMV infection in this HSCT population was high, and the most prevalent genotype in these patients with active CMV infection was gB1 and gB2 genotype (74%). In Brazil, HSCT recipients seem to carry mainly gB1 and gB2 CMV genotype.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1471-2334 1471-2334
DOI:	10.1186/1471-2334-13-310