Mixed infections with distinct cytomegalovirus glycoprotein B genotypes in Polish pregnant women, fetuses, and newborns

M Rycel,Z Gaj,B Zawilińska,E Paradowska,Z Leśnikowski,J Wilczyński,W Wujcicka,D Nowakowska,P Suski

doi:10.1007/s10096-014-2266-9

Abstract

The purpose of this investigation was to describe a distribution of cytomegalovirus (CMV) single and multiple genotypes among infected pregnant women, their fetuses, and newborns coming from Central Poland, as well as congenital cytomegaly outcome. The study involved 278 CMV-seropositive pregnant women, of whom 192 were tested for viral DNAemia. Human cytomegalovirus (HCMV) genotyping was performed for 18 of 34 pregnant women carrying the viral DNA and for 12 of their 15 offspring with confirmed HCMV infections. Anti-HCMV antibodies levels were assessed by chemiluminescence immunoassay (CLIA) and enzyme-linked fluorescence assay (ELFA) tests. Viral DNA loads and genotypes were determined by real-time polymerase chain reaction (PCR) assays for the UL55 gene. In the pregnant women, we identified HCMV gB1, gB2, gB3, and gB4 genotypes. Single gB2, gB3, or gB4 genotypes were observed in 14 (77.8 %) women, while multiple gB1–gB2 or gB2–gB3 genotypes were observed in four (22.2 %). Maternal HCMV genotypes determined the genotypes identified in their fetuses and newborns (p ≤ 0.050). Half of them were infected with single HCMV gB1, gB2, or gB3 genotypes and the other half with multiple gB1–gB2 or gB2–gB3 genotypes. Single and multiple genotypes were observed in both asymptomatic and symptomatic congenital cytomegaly, although no gB3 genotype was identified among asymptomatic cases. In Central Poland, infections with single and multiple HCMV strains occur in pregnant women, as well as in their fetuses and neonates, with both asymptomatic and symptomatic infections. HCMV infections identified in mothers seem to be associated with the viral genotypes in their children.

Highlights

Human cytomegalovirus (HCMV) is the most common cause of intrauterine infections worldwide [1,2,3,4,5]
Nucleotide variability was determined for approximately 20 open reading frames (ORFs) of HCMV that encode, e.g., viral envelope glycoproteins B, H, and N, as well as chemokines and chemokine receptors, like a tumor necrosis factor (TNF)-α receptor [6,7,8,9]
Considering whole blood, the single gB1 genotype was observed in 10.0 % (1/10) of HCMV DNA-positive samples and gB2 in 80.0 % (8/10), while multiple gB2–gB3 genotypes were observed in 10.0 % (1/10)

Summary

Introduction

Human cytomegalovirus (HCMV) is the most common cause of intrauterine infections worldwide [1,2,3,4,5]. Glycoprotein B is the major HCMV envelope protein that has been determined as an important factor for viral in vivo and in vitro replication, as well as for host cell entry, cell-tocell virus transmission, and fusion of infected cells [4, 10,11,12]. The cleavage site and the region between 448 and 481 codons were described as the area of the highest genetic variability [11, 14]. Considering this highly polymorphic site, four main HCMV genotypes, gB1, gB2, gB3, and gB4, and three rare non-prototypic variants, gB5, gB6, and gB7, were defined [11, 14]. An earlier study performed in infants and newborns from Southern Poland demonstrated gB1 (63.5 %) as the most common genotype [14]

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