Differential inhibition of human cytomegalovirus HCMV by toll-like receptor ligands mediated by interferon-beta in human foreskin fibroblasts and cervical tissueReport as inadecuate




Differential inhibition of human cytomegalovirus HCMV by toll-like receptor ligands mediated by interferon-beta in human foreskin fibroblasts and cervical tissue - Download this document for free, or read online. Document in PDF available to download.

Virology Journal

, 4:133

First Online: 05 December 2007Received: 05 October 2007Accepted: 05 December 2007

Abstract

Human cytomegalovirus HCMV can be acquired sexually and is shed from the genital tract. Cross-sectional studies in women show that changes in genital tract microbial flora affect HCMV infection and-or shedding. Since genital microbial flora may affect HCMV infection or replication by stimulating cells through Toll-like receptors TLR, we assessed the effects of defined TLR-ligands on HCMV replication in foreskin fibroblasts and ectocervical tissue. Poly I:C a TLR3-ligand and lipopolysaccharide LPS, a TLR4-ligand inhibited HCMV and induced secretion of IL-8 and Interferon-beta IFNβ in both foreskin fibroblasts and ectocervical tissue. The anti-HCMV effect was reversed by antibody to IFNβ. CpG TLR9 ligand and lipoteichoic acid LTA, TLR2 ligand also inhibited HCMV infection in ectocervical tissue and this anti-HCMV effect was also reversed by anti-IFNβ antibody. In contrast, LTA and CpG did not inhibit HCMV infection in foreskin fibroblasts. This study shows that TLR ligands induce an HCMV-antiviral effect that is mediated by IFNβ suggesting that changes in genital tract flora may affect HCMV infection or shedding by stimulating TLR. This study also contrasts the utility of two models that can be used for assessing the interaction of microbial flora with HCMV in the genital tract. Clear differences in the response to different TLR ligands suggests the explant model more closely reflects in vivo responses to genital infections.

Electronic supplementary materialThe online version of this article doi:10.1186-1743-422X-4-133 contains supplementary material, which is available to authorized users.

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Author: Sailesh C Harwani - Nell S Lurain - M Reza Zariffard - Gregory T Spear

Source: https://link.springer.com/







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