Clinical implications of human cytomegalovirus glycoprotein B among immunocompromised patients in South Korea

Abstract

Background: Human cytomegalovirus glycoprotein B (gB) is highly immunogenic and essential for both in vivo and in vitro viral entry to the host. It is well known that HCMV plays an important role in viral-host interaction. gB genotypes vary based on geographical distributions of global HCMV strains. However, few studies have analyzed gB genotypes and their association with clinical outcome in patients with various underlying diseases. There are no data concerning gB genotypes and their clinical manifestations in South Korea. This study aimed to analyze the gB genotype distribution and its association with clinically significant factors. Methods: This study was performed on 138 HCMV strains obtained from blood samples of 138 patients presenting with various diseases under immunosuppression at a single tertiary center between January 2013 and March 2014. Polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing analysis were used to identify the gB genotypes. Patients' clinical data were obtained from electrical medical records. Results: The frequency of the various immunosuppressive diseases was as follows: 45.7% (63/138) were hematologic malignancies, 22.5% (31/138) were solid organ malignancies, 18.8% (26/138) were infectious diseases with severe sepsis, 10.1% (14/138) were HIV infection, and 3.6% (5/138) were autoimmune diseases. The distribution of HCMV genotypes was as follows: gB1, 98 of 138 (71%); gB2, 1 of 138 (0.72%); and gB3, 39 of 138 (28.3%). Results with respect to previous viremia, previous ganciclovir use, Eastern Cooperative Oncology Group (ECOG) performance scale, acute kidney injury (AKI), shock, and intensive care unit (ICU) stay were not different between gB1 and gB3 among hematologic and solid organ malignancies. However, the duration from hematopoietic stem cell transplantation (HSCT) to HCMV viremia was significantly longer for patients with gB1 infection than for those with gB3 infection (219 (5–912) vs. 57 (20–2099), p=0.04). Regarding AKI, shock, and ICU stay, gB3 was significantly more common than gB1 among infectious diseases with severe sepsis (gB1 vs. gB3, 61.1% (11/18) vs. 75% (6/8), p=0.02; gB1 vs. gB3, 55.6% (10/18) vs. 75% (6/8), p=0.02; and gB1 vs. gB3, 44.4% (8/18) vs. 50% (4/8), p=0.03). No statistically significant difference was found between the occurrence of HCMV disease and genotypes among patients with various diseases under immune suppression (p=0.47). No statistically significant difference was noted between genotypes and all causes of in-hospital mortality (p=0.37). However, all-cause in-hospital mortality was significantly different between gB1 and gB3 among infectious diseases with severe sepsis (gB1 vs. gB3, 12 (66.7%) vs. 6 (75%), p=0.04). Conclusion: We found that the most common genotypes were gB1 (71%, 98/138) and gB3 (28.3%, 39/138) in South Korea, and the duration from HSCT to HCMV viremia was significantly longer for gB1 than for gB3. Regarding AKI, shock, and ICU stay, gB3 was significantly more common than gB1 among infectious diseases with severe sepsis. Based on these results, further studies on viral toxicity assays should be considered for infectious diseases.