Abstract

BackgroundCongenital Cytomegalovirus (CMV) is a very common intrauterine infection which can cause severe developmental disabilities. Transmission of the virus to the fetus occurs in only 40% of primarily infected women. The probability of intrauterine transmission is higher when infection occurs during the second trimester of pregnancy than in the first trimester. The Toll-like receptors (TLRs) protein family plays a key role in both innate immune response to CMV infections and in normal pregnancy. Specific single nucleotide polymorphisms (SNPs) in TLRs can affect CMV infections and maternal–fetal interface expression. Therefore, TLR SNPs could be involved in intrauterine transmission determination.Study aimTo establish a correlation between TLR2 (rs4696480, rs3804100, rs1898830), TLR3 (rs3775291) and TLR7(rs179008) SNPs with CMV intrauterine transmission during the first and second trimester.MethodsSNPs of 83 pregnant women with primary CMV were analyzed by Real-Time PCR and PCR-RFLP assay and compared to intrauterine transmission state.ResultsWomen bearing the GG genotype in the rs1898830 TLR2 SNP who were infected with CMV during the second trimester did not transmit the virus to the fetus. Likewise, in the co-dominant or recessive models of this SNP, a significant association was found between the genotypes and CMV intrauterine transmission. In all cohort women or in women infected during the first trimester, no such associations were found between the tested SNPs and intrauterine transmission of the virus.ConclusionWomen bearing the GG genotype in the rs1898830 SNP, who are infected with CMV during the second trimester of pregnancy, have a low likelihood of transmitting the virus to the fetus.

Highlights

  • Cytomegalovirus (CMV) is the most common cause of congenital infection in the developed world, and can cause a variety of long-term disabilities including mental, hearing and visual impairments [1,2,3]

  • Women bearing the GG genotype in the rs1898830 TLR2 single nucleotide polymorphisms (SNPs) who were infected with CMV during the second trimester did not transmit the virus to the fetus

  • In all cohort women or in women infected during the first trimester, no such associations were found between the tested SNPs and intrauterine transmission of the virus

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Summary

Introduction

Cytomegalovirus (CMV) is the most common cause of congenital infection in the developed world, and can cause a variety of long-term disabilities including mental, hearing and visual impairments [1,2,3]. These severe disabilities threaten more children than well-known childhood maladies such as Down syndrome or fetal alcohol syndrome [4,5]. Pathogen structures activate an intracellular signaling cascade mediated by TLRs, causing induction of antimicrobial genes and inflammatory cytokines This early response to infection is crucial until the pathogen-specific adaptive arm of the immune response is established [7]. TLR SNPs could be involved in intrauterine transmission determination

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