Impact of genetic polymorphisms in cytomegalovirus glycoprotein B on outcomes in solid-organ transplant recipients with cytomegalovirus disease.
BACKGROUND
It is unknown whether specific viral polymorphisms affect in vivo therapeutic response in patients with cytomegalovirus (CMV) disease. Polymorphisms in the CMV glycoprotein B (gB) gene allow discrimination of 4 distinct genotypes (gB1-gB4). We assessed the influence of gB genotypes on the clinical and virologic outcome of CMV disease.


METHODS
Solid-organ transplant recipients enrolled in a multicenter trial of CMV disease treatment (VICTOR study) were included in this study. CMV gB genotyping was performed using quantitative real-time polymerase chain reaction at day 0 (start of antiviral therapy).


RESULTS
Among 239 patients with CMV disease, the prevalence of gB strain types was 26% for gB1, 10% for gB2, 10% for gB3, and 5% for gB4, whereas mixed infections were present in 49%. Donor-seropositive/recipient-seropositive patients were more likely to have mixed gB infection than donor-seropositive/recipient-seronegative patients (40% vs. 12%; P = .001). Median baseline viral loads were higher and time to viral eradication was longer ( P = .006 and P = .026 , respectively) for mixed infection versus infection with a single genotype. In a multivariate model, mixed gB infection was a significant predictor of failure to eradicate virus by day 21 (mixed vs single genotype; odds ratio, 2.66; 95% confidence interval, 1.31-5.38; P = .007 ) after controlling for baseline viral load, CMV serostatus at baseline, ganciclovir resistance, and antiviral treatment. No effect of gB genotype was seen on virologic or clinical CMV recurrence.


CONCLUSIONS
No specific gB genotype appears to confer a specific CMV virulence advantage. However, mixed gB genotype infections are associated with higher viral loads and delayed viral clearance.
Manuel
Oriol
O
Transplant Infectious Diseases and Provincial Laboratory for Public Health (Microbiology), University of Alberta, Edmonton, Alberta, Canada.
Asberg
Anders
A
Pang
Xiaoli
X
Rollag
Halvor
H
Emery
Vincent C
VC
Preiksaitis
Jutta K
JK
Kumar
Deepali
D
Pescovitz
Mark D
MD
Bignamini
Angelo A
AA
Hartmann
Anders
A
Jardine
Alan G
AG
Humar
Atul
A
D000328:Adult; D003587:Cytomegalovirus / Q000235:genetics* / Q000472:pathogenicity*; D003586:Cytomegalovirus Infections / Q000821:virology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects*; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D011183:Postoperative Complications / Q000821:virology; D012008:Recurrence; D012720:Severity of Illness Index; D014759:Viral Envelope Proteins / Q000235:genetics*; D019562:Viral Load; D014774:Virulence
D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus