PRODUCTION AND RELEASE OF CXCL8/IL-8 AND TNF-α BY HaCaT KERATINOCYTES STIMULATED WITH ZIKA VIRUS ENVELOPE PROTEIN.
Cardiff Metropolitan University
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Flaviviruses are associated with important human disease such as dengue fever, yellow fever and recently Zika infection. All this flaviviruses pose an ongoing public health threat as the number of outbreaks are increasing in frequency and case numbers. The causative agent of Zika infection is Zika virus (ZIKV) a mosquito borne flavivirus. Up to 80% of ZIKV infections may be asymptomatic but ZIKV infection has been potentially linked with severe neurological complications such as Guillian-Barre Syndrome and Microcephaly. The ZIKV genome encodes a polyprotein which cleaves into both structural and non-structural proteins. Among the structural proteins is the envelope protein. (ZIKV-E). This protein plays two roles: anchoring the virus to the host target cell surface and providing an important antigen for recognition by the immune system. Due to the mode of ZIKV transmission, cells of the skin (keratinocytes, Langerhans cells, macrophages and T cells) play a critical role in virus recognition and the triggering of the immune response. Although in vitro keratinocytes can be infected with ZIKV, little is known about how ZIKV-E protein interacts with these cells. The present work has looked at this interaction by using the HaCaT cell line as a model system and using commercially available recombinant ZIKV-E protein. Prior to carrying out the experiments, it was hypothesised that the protein will stimulate keratinocytes to produce and release pro-inflammatory chemokines and cytokines such as CXCL8/IL-8 and TNF-α. The results presented here indicate that only when ZIKV-E protein was used above a certain threshold (5 μg/ml) high levels of CXCL8/IL-8 were detected in the culture supernatant. On the contrary, TNF-α was not detected under any of the stimulatory conditions tested. The study also looked at the capacity of ZIKV-E protein to affect the release of CXCL8/IL-8 when HaCaT cells were stimulated with a combination of recombinant ZIKV-E protein and the synthetic bacterial lipopeptide Pam2Cys. The results presented show an inhibitory effect of the recombinant protein on CXCL8/IL-8 release, suggesting that in vivo, ZIKV-E protein could prevent the activation of the innate immune. Moreover, the results presented here could have important implications for the design of vaccines containing ZIKV-E protein supplemented with adjuvants that mimic the action of microbial components. Further work will be needed to confirm and expand the results presented to better understand the role of ZIKV-E protein during the activation of the immune system.
BSc Biomedical Science
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