Zika Virus Infection Preferentially Counterbalances Human Peripheral Monocyte and/or NK Cell Activity

ABSTRACT Zika virus (ZIKV) has reemerged in the population and caused unprecedented global outbreaks. Here, the transcriptomic consequences of ZIKV infection were studied systematically first in human peripheral blood CD14+ monocytes and monocyte-derived macrophages with high-density RNA sequencing....

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Autores principales:	Fok-Moon Lum, David Lee, Tze-Kwang Chua, Jeslin J. L. Tan, Cheryl Y. P. Lee, Xuan Liu, Yongxiang Fang, Bernett Lee, Wearn-Xin Yee, Natasha Y. Rickett, Po-Ying Chia, Vanessa Lim, Yee-Sin Leo, David A. Matthews, Julian A. Hiscox, Lisa F. P. Ng
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	NK cells RNA-seq Zika virus immune response monocytes transcriptomes Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/a2c1b7af0c0a4416afc93a93d328a15a
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spelling	oai:doaj.org-article:a2c1b7af0c0a4416afc93a93d328a15a2021-11-15T15:22:14ZZika Virus Infection Preferentially Counterbalances Human Peripheral Monocyte and/or NK Cell Activity10.1128/mSphereDirect.00120-182379-5042https://doaj.org/article/a2c1b7af0c0a4416afc93a93d328a15a2018-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphereDirect.00120-18https://doaj.org/toc/2379-5042ABSTRACT Zika virus (ZIKV) has reemerged in the population and caused unprecedented global outbreaks. Here, the transcriptomic consequences of ZIKV infection were studied systematically first 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 cross talk between monocytes and natural killer (NK) cells as one of the highly identified pathways. Immunophenotyping 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 gamma interferon (IFN-γ) 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. IMPORTANCE ZIKV reemerged in recent years, causing outbreaks in many parts of the world. Alarmingly, ZIKV infection has been associated with neurological complications such as Guillain-Barré syndrome (GBS) in adults and congenital fetal growth-associated anomalies in newborns. Host peripheral immune cells are one of the first to interact with the virus upon successful transmission from an infected female Aedes mosquito. However, little is known about the role of these immune cells during infection. In this work, the immune responses of monocytes, known target cells of ZIKV infection, were investigated by high-density transcriptomics. The analysis saw a robust immune response being elicited. Importantly, it also divulged that monocytes prime NK cell activities during virus infection. Removal of monocytes during the infection changed the immune milieu, which in turn reduced NK cell stimulation. This study provides valuable insights into the pathobiology of the virus and allows for the possibility of designing novel targeted therapeutics.Fok-Moon LumDavid LeeTze-Kwang ChuaJeslin J. L. TanCheryl Y. P. LeeXuan LiuYongxiang FangBernett LeeWearn-Xin YeeNatasha Y. RickettPo-Ying ChiaVanessa LimYee-Sin LeoDavid A. MatthewsJulian A. HiscoxLisa F. P. NgAmerican Society for MicrobiologyarticleNK cellsRNA-seqZika virusimmune responsemonocytestranscriptomesMicrobiologyQR1-502ENmSphere, Vol 3, Iss 2 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	NK cells RNA-seq Zika virus immune response monocytes transcriptomes Microbiology QR1-502
spellingShingle	NK cells RNA-seq Zika virus immune response monocytes transcriptomes Microbiology QR1-502 Fok-Moon Lum David Lee Tze-Kwang Chua Jeslin J. L. Tan Cheryl Y. P. Lee Xuan Liu Yongxiang Fang Bernett Lee Wearn-Xin Yee Natasha Y. Rickett Po-Ying Chia Vanessa Lim Yee-Sin Leo David A. Matthews Julian A. Hiscox Lisa F. P. Ng Zika Virus Infection Preferentially Counterbalances Human Peripheral Monocyte and/or NK Cell Activity
description	ABSTRACT Zika virus (ZIKV) has reemerged in the population and caused unprecedented global outbreaks. Here, the transcriptomic consequences of ZIKV infection were studied systematically first 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 cross talk between monocytes and natural killer (NK) cells as one of the highly identified pathways. Immunophenotyping 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 gamma interferon (IFN-γ) 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. IMPORTANCE ZIKV reemerged in recent years, causing outbreaks in many parts of the world. Alarmingly, ZIKV infection has been associated with neurological complications such as Guillain-Barré syndrome (GBS) in adults and congenital fetal growth-associated anomalies in newborns. Host peripheral immune cells are one of the first to interact with the virus upon successful transmission from an infected female Aedes mosquito. However, little is known about the role of these immune cells during infection. In this work, the immune responses of monocytes, known target cells of ZIKV infection, were investigated by high-density transcriptomics. The analysis saw a robust immune response being elicited. Importantly, it also divulged that monocytes prime NK cell activities during virus infection. Removal of monocytes during the infection changed the immune milieu, which in turn reduced NK cell stimulation. This study provides valuable insights into the pathobiology of the virus and allows for the possibility of designing novel targeted therapeutics.
format	article
author	Fok-Moon Lum David Lee Tze-Kwang Chua Jeslin J. L. Tan Cheryl Y. P. Lee Xuan Liu Yongxiang Fang Bernett Lee Wearn-Xin Yee Natasha Y. Rickett Po-Ying Chia Vanessa Lim Yee-Sin Leo David A. Matthews Julian A. Hiscox Lisa F. P. Ng
author_facet	Fok-Moon Lum David Lee Tze-Kwang Chua Jeslin J. L. Tan Cheryl Y. P. Lee Xuan Liu Yongxiang Fang Bernett Lee Wearn-Xin Yee Natasha Y. Rickett Po-Ying Chia Vanessa Lim Yee-Sin Leo David A. Matthews Julian A. Hiscox Lisa F. P. Ng
author_sort	Fok-Moon Lum
title	Zika Virus Infection Preferentially Counterbalances Human Peripheral Monocyte and/or NK Cell Activity
title_short	Zika Virus Infection Preferentially Counterbalances Human Peripheral Monocyte and/or NK Cell Activity
title_full	Zika Virus Infection Preferentially Counterbalances Human Peripheral Monocyte and/or NK Cell Activity
title_fullStr	Zika Virus Infection Preferentially Counterbalances Human Peripheral Monocyte and/or NK Cell Activity
title_full_unstemmed	Zika Virus Infection Preferentially Counterbalances Human Peripheral Monocyte and/or NK Cell Activity
title_sort	zika virus infection preferentially counterbalances human peripheral monocyte and/or nk cell activity
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/a2c1b7af0c0a4416afc93a93d328a15a
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Zika Virus Infection Preferentially Counterbalances Human Peripheral Monocyte and/or NK Cell Activity

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