Ocena związku poziomu wiremii HCMV u matki z przebiegiem ciąży i stanem urodzeniowym noworodków

Congenital cytomegaly is caused by intrauterine mother-to-fetus HCMV transmission and constitutes the most common vertical infection. Objectives: The aim of the study was to analyze the viremia level in maternal blood and its influence on the course and duration of pregnancy, as well as newborn condition. Material and methods: The material included blood samples collected from 117 pregnant women with serological features of HCMV infection and from 29 neonates hospitalized at DFMMG in Lodz between 1999 and 2009. The presence of HCMV DNA in the maternal and fetal blood was tested using real-time PCR. Results: Prevalence of maternal viremia was observed to increase the risk of viremia in neonates, as compared to children born to mothers with no viremia. However, lack of HCMV DNA in maternal blood does not exclude fetal infection in utero. Newborn condition assessed by Apgar scores was significantly lower in the group of infants born to mothers with serological features of acute cytomegaly (pWrodzona cytomegalia wywołana transmisją wirusa cytomegalii (HCMV) od matki do płodu, jest najczęstszym zakażeniem wertykalnym. Cel pracy: Celem pracy była ocena poziomu wiremii u kobiet ciężarnych i jej wpływu na przebieg i czas trwania ciąży oraz stan urodzeniowy noworodków. Materiał i metody: Materiałem do badań była krew pobrana od 117 ciężarnych z serologicznymi cechami zakażenia HCMV oraz 29 noworodków hospitalizowanych w Klinice Medycyny Matczyno-Płodowej i Ginekologii Instytutu Centrum Zdrowia Matki Polki w latach 1999-2009. Liczba kopii DNA HCMV we krwi matek i dzieci oznaczana była metodą PCR w czasie rzeczywistym (real-time PCR). Wyniki: Stwierdzono, że występowanie wiremii HCMV u matki zwiększa ryzyko występowania wiremii u noworodków w porównaniu z ryzykiem u dzieci matek bez wiremii, jednakże brak DNA HCMV we krwi matki nie wyklucza zakażenia płodu in utero. Stan urodzeniowy noworodków oceniany w skali Apgar był istotnie niższy w grupie noworodków urodzonych przez matki z serologicznymi cechami ostrej cytomegalii (

TLR9 2848 GA heterozygotic status possibly predisposes fetuses and newborns to congenital infection with human cytomegalovirus.

Some single nucleotide polymorphisms (SNP), located in Toll-like receptor (TLR) genes, were reported to be associated with human cytomegalovirus (HCMV) infections. The study was aimed to assess the correlation of SNPs at TLR4 and TLR9 genes with the occurrence of congenital cytomegaly, based on available samples.Reported case-control study included both HCMV infected and non-infected fetuses and newborns. The specimens were classified to the molecular analyses, based on serological features of the recent infection and HCMV DNAemia in body fluids. TLR SNPs were studied, using multiplex nested PCR-RFLP assay, and determined genotypes were confirmed by sequencing. Hardy-Weinberg equilibrium was assessed for the identified genotypes. The linkage disequilibrium was also estimated for TLR4 SNPs. A relationship between the status of TLR genotypes and congenital cytomegaly development was estimated, using a logistic regression model.Hardy Weinberg equilibrium was observed for almost all SNPs, both infected and non-infected patients, with exception of TLR4 896 A>G polymorphism in the control group (P≤0.050). TLR4 896 A>G and 1196 C>T SNPs were found in linkage disequilibrium in both study groups (P≤0.050). The CC genotype at TLR4 1196 SNP and the GA variant at TLR9 2848 G>A SNP were significantly associated with HCMV infection (P≤0.050). The risk of congenital cytomegaly was higher in heterozygotes at TLR9 SNP than in the carriers of other genotypic variants at the reported locus (OR 4.81; P≤0.050). The GC haplotype at TLR4 SNPs and GCA variants at TLR4 and TLR9 SNPs were significantly associated with HCMV infection (P≤0.0001). The ACA variants were more frequent among fetuses and neonates with symptomatic, rather than asymptomatic cytomegaly (P≤0.0001).TLR4 and TLR9 polymorphisms may contribute to the development of congenital infection with HCMV in fetuses and neonates. The TLR9 2848 GA heterozygotic status possibly predisposes to HCMV infection, increasing the risk of congenital cytomegaly development

Association of TLR3 L412F Polymorphism with Cytomegalovirus Infection in Children.

Intracellular Toll-like receptor 3 (TLR3) recognizes viral double-stranded RNA (dsRNA) and activates antiviral immune responses through the production of type I interferons (IFNs) and inflammatory cytokines. This receptor binds to dsRNA molecules produced during human cytomegalovirus (HCMV) replication. TLR7 senses viral single-stranded RNA (ssRNA) in endosomes, and it can interact with endogenous RNAs. We determined the genotype distribution of single-nucleotide polymorphisms (SNPs) within the TLR3 and TLR7 genes in children with HCMV infection and the relationship between TLR polymorphisms and viral infection. We genotyped 59 children with symptomatic HCMV infection and 78 healthy individuals for SNPs in the TLR3 (rs3775290, c.1377C>T, F459F; rs3775291, c.1234C>T, L412F; rs3775296, c.-7C>A) and TLR7 (rs179008, c.32A>T, Q11L; rs5741880, c.3+1716G>T) genes. SNP genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and capillary electrophoresis. The HCMV DNA load was quantified by real-time PCR. We found an increased frequency of the heterozygous genotype TLR3 L412F in children with HCMV infection compared with uninfected cases. In individuals with a mutation present in at least one allele of the L412F SNP, an increased risk of HCMV disease was found, and this result remained highly significant after Bonferroni's correction for multiple testing (Pc < 0.001). The heterozygous genotype of this SNP was associated with the increased risk of HCMV disease in an adjusted model that included the HCMV DNA copy number in whole blood and urine (P < 0.001 and P = 0.008, respectively). Moreover, those with a heterozygous genotype of rs3775296 showed an increased relative risk of HCMV infection (P = 0.042), but this association did not reach statistical significance after correction for multiple testing. In contrast, the rs3775290 SNP of TLR3 and TLR7 SNPs were not related to viral infection. A moderate linkage disequilibrium (LD) was observed between the SNPs rs3775291 and rs3775296 (r2 = 0.514). We suggest that the L412F polymorphism in the TLR3 gene could be a genetic risk factor for the development of HCMV disease