Combined genetic variants of human cytomegalovirus envelope glycoproteins as congenital infection markers

Abstract

BackgroundHuman cytomegalovirus (HCMV) is still considered to be the main viral cause of birth defects and long-term neurological and sensory sequelae following congenital infection.Several Authors sustain a key role of HCMV envelope glycoproteins, such as gB, gN and gO - mainly involved in cell targeting, viral penetration and spread - as putative virulence factors. The genes coding for these glycoproteins possess hypervariable regions, resulting in a number of genetic variants in circulating clinical strains. Considering that the genetic polymorphisms underlying the specific differences between gB, gN and gO genotypes can influence the ability of HCMV to preferentially target specific host cells, it is very likely that they play an important role in defining HCMV infection outcome.In the present study, we analysed HCMV gB, gN and gO gene polymorphisms in viral strains isolated from paediatric patients with congenital or post-natal infection, to investigate whether specific genetic variants may be associated with congenital infection.MethodsThe restriction fragment polymorphisms of genes coding for HCMV gB (UL55), gN (UL73) and gO (UL74) were investigated by analysing viral DNA extracted from 40 urine samples of as many paediatric patients with congenital or post-natal HCMV infection. Randomly selected samples were subjected to DNA sequencing and phylogenetic analysis. Statistical analysis was performed using Fisher’s exact test to assess the significance of single and combined glycoprotein genotypes frequency distribution. Statistical significance was considered at a P <0.05.ResultsWhile gB genomic variants were quite homogeneously represented in both paediatric groups, the gN4 genotype significantly prevailed in congenitally infected children (89.5 %) vs post-natally infected children (47.6 %), with a predominance of the gN4c variant (47.4 %). A similar trend was observed for gO3 (52.6 % vs 19 %).Concerning genotypes association, a statistically significant (P = 0.037) gN4-gO3 combination was found specifically in the congenitally infected group.ConclusionsThe results indicate that the gN4 (mostly the gN4c variant) and gO3 combined genotypes could provide useful markers of congenital infection and represent suitable candidate molecules for prophylactic vaccine preparations.

Genotypes of glycoprotein B gene among the Indian symptomatic neonates with congenital CMV infection

“…A report by Firth et al, 2016 and Lachmann et al, 2018 also explained the higher incidence of CMV in female patients [46, 47]. Genetic polymorphisms of envelope glycoproteins among circulating CMV strains are generally considered as probable virulence indicators [48], and may be accountable for differential CMV tropism to precise cell types and differential capacity to distribute and interfere with normal tissue growth [30, 39]. Previous reports show that four gB genotypes of CMV are observed in congenital cytomegaly [48, 49].…”

“…Genetic polymorphisms of envelope glycoproteins among circulating CMV strains are generally considered as probable virulence indicators [48], and may be accountable for differential CMV tropism to precise cell types and differential capacity to distribute and interfere with normal tissue growth [30, 39]. Previous reports show that four gB genotypes of CMV are observed in congenital cytomegaly [48, 49]. Several studies reported that cCMV infections among Costa Rican, Indian and Chinese infants were caused by gB1, gB2, and gB3 genotypes [29, 42].…”

“…Intra-host viral diversity and genomic variation have recently been characterized by next-generation sequencing, showing similar genomic variability in different RNA viruses [48, 49] [57, 58]. Mixed populations of the glycoprotein genotype have been previously documented in congenitally infected neonates and in pregnant women [59].…”

Human cytomegalovirus glycoprotein polymorphisms and increasing viral load in AIDS patients

“…According to the sequence variation of UL55 gene that encodes gB, there are four major gB genotypes(gB1, gB2, gB3, gB4) [ 10 – 13 ]. In addition, three nonprototypic genotypes (gB5, gB6, gB7) have been identified [ 14 ] [ 15 ].…”

Human cytomegalovirus envelope glycoprotein B, H, and N polymorphisms among infants of Shanghai area in China

“…Envelope glycoproteins are involved in viral entry and cell‐to‐cell virus transmission 7,8 . HCMV glycoprotein B (gB), encoded by ORF UL55, is the most widely studied envelope glycoprotein and has four main gB genotypes: gB1, gB2, gB3, and gB4 3,9‐13 . gB is a component of the envelope complex gC‐I and an important target of humoral and cellular immune responses, which is involved in virus attachment and entry, cell‐to‐cell virus transmission, and fusion of infected cells 2,7,9,14‐18 .…”