Distinct genotypic distributions of cytomegalovirus (CMV) envelope glycoprotein in bone marrow and renal transplant recipients with CMV disease

Abstract

A prospective study of the spectrum of glycoprotein B (gB) and glycoprotein H (gH) genotypes of cytomegalovirus (CMV) was conducted with five categories of patients: viremic bone marrow-transplant (BMT) recipients who developed CMV disease after BMT (n ‫؍‬ 22), viremic BMT recipients without CMV disease (n ‫؍‬ 11), viremic renal-transplant recipients who developed CMV disease after transplantation (n ‫؍‬ 14), viremic renal-transplant recipients without CMV disease (n ‫؍‬ 13), and premature babies with asymptomatic congenital CMV infections (n ‫؍‬ 13). Genotypic stability was observed because the gB and gH genotypes of multiple isolates obtained from a single patient were identical. The distribution of gH genotypes in patients of all groups studied were similar. However, there was a unique distribution of the gB genotype in the first category of patients, i.e., BMT recipients with CMV disease, which was distinct from those of all other categories (P < 0.05). CMV isolates from 54% of BMT recipients with CMV disease exhibited gB type 2, while isolates from 46, 50, 69, and 77% of the BMT recipients without CMV disease, renal-transplant recipients with and those without CMV disease, and premature babies with congenital CMV infection, respectively, were of gB type 1. An analysis of the clinical characteristics of BMT recipients with CMV disease indicated that all underwent either an allogeneic or matched, unrelated donor transplant, and half had severe acute graft-versus-host disease (grades 2 to 4). The statistically significant genotypic difference between CMV isolates from BMT recipients with and without CMV disease was not observed between isolates from renal-transplant recipients with and without CMV disease. We speculate that differences in pathogenesis in different patient groups might account for these observations. These findings would also facilitate decision making about the choice of recombinant CMV glycoprotein vaccine required to immunize transplant donors and the subsequent adoptive transfer of immunity to BMT recipients. When the source of CMV DNA required for genotyping was investigated among renal-transplant recipients, direct use of peripheral blood leukocytes was 95% effective compared to the effectiveness of cells obtained from conventional culture of peripheral blood specimens.

Prevalence and genotype distribution of cytomegalovirus UL55 sequence in renal transplant recipients in north west of Iran

“…In the present study, one third of the recipients were infected with more than one genotype. These data were in contrast to 96.3% and 90% of patients infected with only one gB genotype reported in previous studies on renal transplant recipients [Woo et al, 1997b;Carraro and Granato, 2003a]. Previous reports have implied that immunocompromised people including pregnant women [Boppana et al, 2001] can have dual [Baldanti et al, 1998] or multiple [Thomas et al, 2001] CMV infections.…”

“…Similar to other reports [Aquino and Figueiredo, 2000;Carraro and Granato, 2003b], genotype gB4 was rarely found (5.9%) in our recipients. Predominance of gB1 genotype was reported more frequently among the renal transplant recipients [Woo et al, 1997a] and congenitally infected newborns [Bale et al, 2000]. However, high prevalence of gB2 genotype has been found by other studies in renal transplant recipients [Carraro and Granato, 2003b], HIVinfected patients [Fidouh-Houhou et al, 2001], or CMV retinitis [Shepp et al, 1996].…”

Genetic polymorphisms among human cytomegalovirus (HCMV) wild‐type strains

“…As far as the solid organ transplant recipients are concerned, gB types have been in some cases associated with pathologies: gB-1 is related to Genetic polymorphisms among HCMV strains Genetic polymorphisms among HCMV strains 397 397 Genetic polymorphisms among HCMV strains Genetic polymorphisms among HCMV strains 401 401 and Aquino et al [120], but gB-1 also associates with milder pathogenic properties and with live related donors, according to Pacsa et al [147]. However, in most cases, the results showed no correlation of the gB types with the development or clinical outcome of HCMV disease or with organ rejection in this patient population [24,117,129,146,148]. Bone marrow transplant (BMT) recipients have also been studied.…”

“…However, in vitro propagation of virus may affect isolation of strains, so that some variants may be overlooked. Moreover, most data presented indicate that, despite the hypervariability among unrelated strains, UL55, UL73, UL75 and UL144 sequences do not change during in vivo passage in the same host [26,38,53,116,117].…”

“…with ! 2 different HCMV strains, which often occurs in AIDS patients, whereas simultaneous infections with multiple cytomegalovirus strains are less common in other patient populations [117,120,129]. The distance between the loci examined to find a significant association of genetic polymorphisms must also be considered.…”