Cytomegalovirus glycoprotein H genotype distribution and the relationship with hearing loss in children

Abstract

Cytomegalovirus (CMV) is a leading cause of congenital infection and a leading infectious cause of hearing loss in children. The ORF UL75 gene encodes envelope glycoprotein H (gH), which is essential for CMV entry into host cells and the target of the immune response in humans. However, the distribution of gH variants and the relationship between the viral genotype, viral load, and sequelae in children infected with CMV is debated. The UL75 genetic variation of CMV isolates from 42 newborns infected congenitally with CMV and 93 infants with postnatal or unproven congenital CMV infection was analyzed. Genotyping was performed by analysis of PCR-amplified fragments, and the viral load was measured by quantitative real-time PCR. There were no differences in the distribution of gH genotypes in the children infected congenitally and postnatally. Mixed-genotype infections with both gH1 and gH2 variants were detected in approximately 25% of the examined patients. No relationship between UL75 gene polymorphisms and the symptoms at birth was observed. The results suggest that the infection with gH2 genotype diminishes the risk of hearing loss in children (P = 0.010). In addition, sensorineural hearing loss was associated with CMV gH1 genotype infection in infants (P = 0.032) and a high viral load in urine (P = 0.005). In conclusion, it was found that the gH genotype does not predict clinical sequelae in newborn infants following congenital CMV infection. However, these results suggest that the gH genotype might be associated with hearing loss in children.

Epidemiological characteristics of human cytomegalovirus infection and glycoprotein H genotype in Chinese children

“…On the other hand, the investigation of Guo et al did not find any mixedgenotype infections, while Paradowska's investigation revealed mixed-genotype infections which were caused by both genotypes gH1 and gH2, comprising up to 25% of all cases of associated infections. 14 It is noteworthy that we found the highest gH2 HCMV distribution in the age group of newborns, whereas the highest rate of spread of gH1 HCMV was detected in the age group of >3 months. Excepting the one age group of 28De3 months, as age increased, the proportion of gH1 HCMV increased but the proportion of gH2 HCMV decreased.…”

“…19 Our results were in contrast to those of a study conducted by Paradowska et al in Poland, in which the authors found that HCMV infections in children were most commonly caused by the HCMV gH2 genotype. 14 In China, the findings of Guo et al for children residing in the city of Wuhan showed that 62 strains were of the gH1 genotype (60.8%, 62/102), whereas 40 strains were of the gH2 (39.2%, 40/102). In this study, we obtained similar results to Gao et al 20 These findings may indicate that gH1 HCMV is a major genotype in Chinese children.…”

Genotype Distribution, Viral Load and Clinical Characteristics of Infants with Postnatal or Congenital Cytomegalovirus Infection

“…Furthermore, in a study by Yu et al [24] , infants with UL55 genotype 1 and symptomatic CMV disease were diagnosed with CMV related liver disease more frequently. Two other recent studies by Paradowska et al [30] , [31] suggest that certain other CMV genotypes (UL73/gN and UL75/gH, respectively) may predict neurological dysfunction (gN4 genotype) or hearing loss and higher viral load (gH1 genotype) in congenitally and postnatally or unproven congenitally infected infants. Several studies on congenital CMV infection have suggested that blood and urine CMV loads may be important markers of CMV disease severity [24] , [25] , [31] – [34] .…”

“…Two other recent studies by Paradowska et al [30] , [31] suggest that certain other CMV genotypes (UL73/gN and UL75/gH, respectively) may predict neurological dysfunction (gN4 genotype) or hearing loss and higher viral load (gH1 genotype) in congenitally and postnatally or unproven congenitally infected infants. Several studies on congenital CMV infection have suggested that blood and urine CMV loads may be important markers of CMV disease severity [24] , [25] , [31] – [34] . It was recently documented that infants with postnatal CMV infection have significantly lower urine CMV load than infants with congenital CMV infection [35] .…”

High-Throughput Analysis of Human Cytomegalovirus Genome Diversity Highlights the Widespread Occurrence of Gene-Disrupting Mutations and Pervasive Recombination

“…These findings have spiked the interest of clinical virologists in identifying potential correlations between genetic variants and the pathogenic potential of different isolates. Several studies have found some evidence to correlate specific genotypes with disease outcome, investigating polymorphisms in the UL55 (glycoprotein B) (16)(17)(18)(19), UL73 (glycoprotein N) (20)(21)(22), UL75 (glycoprotein H) (23), UL144 (tumor necrosis factor alpha [TNF-␣]-like receptor) (24)(25)(26), and UL146 and UL147 (viral CXCL chemokines) (27,28) genes. Others, however, found no evidence of these relationships (29)(30)(31)(32).…”