Zika virus infection preferentially counterbalances human peripheral monocyte and/or NK-cell activity

Lum, F. M.; Lee, D.; Chua, T.-K.; Tan, J. J.; Lee, C. Y.; Liu, X.; Fang, Y.; Lee, B.; Yee, W.-X.; Rickett, N.; Chia, P.-Y.; Lim, V.; Leo, Y.-S.; Matthews, D.; Hiscox, J.; Ng, L. F.

doi:10.1101/225102

bioRxiv · 10.1101/225102

Zika virus infection preferentially counterbalances human peripheral monocyte and/or NK-cell activity

Lum, F. M.·Lee, D.·Chua, T.-K.·Tan, J. J.·Lee, C. Y.·Liu, X.·Fang, Y.·Lee, B.·Yee, W.-X.·Rickett, N.·Chia, P.-Y.·Lim, V.·Leo, Y.-S.·Matthews, D.·Hiscox, J.·Ng, L. F.

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Abstract

Zika virus (ZIKV) has re-emerged in the population and caused unprecedented global outbreaks. Here, the transcriptomic consequences of ZIKV infection were studied systematically firstly in human peripheral blood CD14+ monocytes and monocyte-derived macrophages with high density RNA-sequencing. Analyses of the ZIKV genome revealed that the virus underwent genetic diversification and differential mRNA abundance was found in host cells during infection. Notably, there was a significant change in the cellular response with crosstalk between monocytes and natural killer (NK) cells as one of the highly identified pathway. Immune-phenotyping of peripheral blood from ZIKV-infected patients further confirmed the activation of NK cells during acute infection. ZIKV infection in peripheral blood cells isolated from healthy donors led to the induction of IFN{gamma} and CD107a -- two key markers of NK-cell function. Depletion of CD14+ monocytes from peripheral blood resulted in a reduction of these markers and reduced priming of NK cells during infection. This was complemented by the immunoproteomic changes observed. Mechanistically, ZIKV infection preferentially counterbalances monocyte and/or NK-cell activity, with implications for targeted cytokine immunotherapies.

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Lum, F. M., Lee, D., Chua, T.-K., Tan, J. J., Lee, C. Y., Liu, X., Fang, Y., Lee, B., Yee, W.-X., Rickett, N., Chia, P.-Y., Lim, V., Leo, Y.-S., Matthews, D., Hiscox, J., Ng, L. F.. 2017-11-25. Zika virus infection preferentially counterbalances human peripheral monocyte and/or NK-cell activity. https://doi.org/10.1101/225102

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