[Genotyping of viral glycoprotein B (gB) in hematopoietic stem cell transplant recipients with active cytomegalovirus infection: analysis of the impact of gB genotypes on the patients' outcome].
OBJECTIVE
Genetic variation of CMV strains may correlate with their pathogenicity for immunocompromised patients. On the basis of sequence variation in the UL55 gene encoding the most abundant viral envelope glycoprotein gB, CMV can be classified into four major gB genotypes. The aim of the study was the analysis of the distribution of gB genotypes in a cohort of haematopoietic stem cell transplant (HSCT) recipients and of the correlation of genetic polymorphisms with clinical outcomes and manifestation of CMV infection.


METHODS
Archived DNA isolates from consecutive blood samples of 53 adult allogeneic HSCT recipients with active CMV infection, transplanted in 2004-2005, were used for the genetic analysis. HCMV gB genotyping was performed by restriction fragment length polymorphism (RFLP) analysis and sequencing of the central variable region of UL55. The association of gB genotypes with selected clinical parameters was assessed by multivariate analysis after adjustment for graft donor type, HLA-matching and anti-thymocyte immunoglobulin (ATG) therapy.


RESULTS
gB1, gB2, gB3, and gB4 genotypes were detected in 30%, 17%, 26% and 4% of the patients, respectively. An atypical gB genotype was found in one patient. Co-infection with two or more gB genotypes was revealed in 17% of the patients. The distribution of gB genotypes did not vary in time, despite the fact that the patients transplanted in 2005 had more severe CMV infection with higher viral loads in the blood than those transplanted in 2004. gB1 was associated with a lower viral load (p = 0.046) and a milder course of symptomatic CMV infection, but with a higher rate of acute graft versus host disease (OR 3.4; p = 0.067). Pancytopenia was less frequent in the patients infected with gB3 (OR 0.09; p = 0.075). In contrast, gB2-infected patients had a worse outcome of CMV infection with a higher rate of organ involvement and were less responsive to antiviral therapy (OR 6.65 and 0.18; p = 0.15 and 0.12, respectively). The prognostic impact of co-infection with two or more gB genotypes was not shown.


CONCLUSIONS
gB genotype may have an impact on the course of CMV infection and its complications in HSCT recipients. Nevertheless, these results need to be tested on a larger group of patients in the context of genetic variability of other functionally important viral genes. The characterization of viral genetic factors determining CMV pathogenesis will be of relevance to the treatment of patients at high risk of CMV infection.
Roubalová
K
K
Vidia s.r.o., Vestec, Praha. kroubalova@vidia.cz
Strunecký
O
O
Zufanová
S
S
Procházka
B
B
Vitek
A
A
D000328:Adult; D000956:Antigens, Viral / Q000097:blood; D003587:Cytomegalovirus / Q000235:genetics*; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000209:etiology / Q000821:virology*; D005838:Genotype; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D010750:Phosphoproteins / Q000097:blood; D012150:Polymorphism, Restriction Fragment Length; D014759:Viral Envelope Proteins / Q000235:genetics*; D014763:Viral Matrix Proteins / Q000097:blood
D000956:Antigens, Viral; D010750:Phosphoproteins; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; C040495:glycoprotein B, Simplexvirus