Journal Article

Impact of Genetic Polymorphisms in Cytomegalovirus Glycoprotein B on Outcomes in Solid-Organ Transplant Recipients with Cytomegalovirus Disease

Oriol Manuel, Anders Åsberg, Xiaoli Pang, Halvor Rollag, Vincent C. Emery, Jutta K Preiksaitis, Deepali Kumar, Mark D. Pescovitz, Angelo A. Bignamini, Anders Hartmann, Alan G. Jardine and Atul Humar

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 49, issue 8, pages 1160-1166
Published in print October 2009 | ISSN: 1058-4838
Published online October 2009 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/605633
Impact of Genetic Polymorphisms in Cytomegalovirus Glycoprotein B on Outcomes in Solid-Organ Transplant Recipients with Cytomegalovirus Disease

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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=.005 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.

Journal Article.  3806 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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