Involvement of TLR2 in the recognition of rubella virus envelope glycoprotein E1
Cardiff Metropolitan University
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Rubella virus (RV), is a positive-strand RNA enveloped virus and the only member of the genus Rubivirus in the family Togaviridae. RV infection generally causes a mild disease when acquired post-natally. However, when the infection occurs in the first gestational trimester it frequently results in severe damage of the foetus and typical congenital defects. RV infection is still endemic in many developing countries. It is known that the host immune response against RV involves recognition of its two envelope glycoproteins, E1 and E2. However, E1 is the dominant surface molecule and main target for the host immune system. It elicits both humoral and cellular responses. Little is known, however, about the initial interaction of RV with the target respiratory epithelium, the nature of the RV receptor in host cells, and the mechanism leading to recognition of, and response to RV by the innate immune system. Given the critical role played by the Toll-like receptor (TLR) family of innate immune receptors in viral recognition, it was the ultimate aim of this project to test whether a main TLR family member, TLR2, is involved in the initial interaction of RV with the respiratory epithelium through recognition of the RV El glycoprotein. Specifically, it was tested whether: 1) respiratory epithelial cells can be activated by RV E1, 2) TLR2 is expressed in respiratory epithelial cells, and 3) TLR2 is involved in RV E1-induced cell activation and responses. To address these issues, the bronchial epithelial cell line, Calu-3, was used as a model system. It was found that: i) Calu-3 cells respond to RV E1 stimulation by producing chemokines, ii) TLR2 is expressed at low levels at the cell surface, but a substantial intracellular pool is maintained, iii) RV E1-induced chemokine release by Calu-3 cells can be abrogated by blocking TLR2, and that iv) the RV E1 protein up-modulates TLR2 cell-surface expression. Together, these findings suggest that the RV E1 envelope glycoprotein is involved in the initial viral interaction with cells of the respiratory tract, and that host recognition of RV E1 requires the activity of TLR2. These findings increase our knowledge of the interaction of RV with the respiratory epithelium, which is crucial to a better understanding of the initial molecular events leading to persistent infection of the foetus with RV during primary maternal infection acquired early in pregnancy.
MSc Biomedical Science
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