Silent infection of human dendritic cells by African and Asian strains of Zika virus

Nathalie J Vielle,Beatrice Zumkehr,Didier Musso,Artur Summerfield,Obdulio García-Nicolás,Miloš Stojanov,Fabian Blank,Marco P Alves,David Baud

doi:10.1038/s41598-018-23734-3

Nathalie J Vielle, Beatrice Zumkehr + Show 7 more

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https://doi.org/10.1038/s41598-018-23734-3

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While Zika virus (ZIKV) circulated for decades (African lineage strains) without report of outbreaks and severe complications, its emergence in French Polynesia and subsequently in the Americas (Asian lineage strains) was associated with description of severe neurological defects in newborns/neonates and adults. With the aim to identify virus lineage-dependent factors, we compared cell susceptibility, virus replication, cell death and innate immune responses following infection with two African and three contemporary Asian lineage strains of ZIKV. To this end, we used green monkey Vero and Aedes albopictus C6/36 cells and human monocyte-derived dendritic cells (DCs). The latter are involved in the pathogenesis of several mosquito-borne Flavivirus infections. In Vero and C6/36 cells, we observed strain- but not lineage-dependent differences in infection profiles. Nevertheless, in human DCs, no significant differences in susceptibility and virus replication were found between lineages and strains. ZIKV induced antiviral interferon type I/III in a limited fashion, with the exception of one African strain. None of the strains induced cell death or DC maturation in terms of MHC II, CD40, CD80/86 or CCR7 expression. Taken together, our data suggest that a large collection of virus isolates needs to be investigated before conclusions on lineage differences can be made.

Highlights

Zika virus (ZIKV) is an emerging mosquito-borne Flavivirus of the Flaviviridae family causing congenital ZIKV syndrome, including microcephaly, and severe neurological complications in adults[1,2]
They express a number of pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) that lead to the activation of the interferon (IFN) pathway and subsequent transcription of interferon-stimulated genes (ISGs) such as Viperin, MxA (Myxovirus resistance gene A), and 2′,5′-OAS (2′,5′-oligoadenylate synthase)[21,22]
The emerging ZIKV strains used were isolated from human patient specimens infected in French Polynesia (PF13/25013-18, referred to as “French Polynesia in 2013 (FP-2013)”), in Puerto Rico (PRVABC59, referred to as “Puerto Rico in 2015 (PR-2015)”) and in Guadeloupe (PHE_semen_Guadeloupe referred to as “G-2016”) (Fig. 1A)

Summary

Introduction

Zika virus (ZIKV) is an emerging mosquito-borne Flavivirus of the Flaviviridae family causing congenital ZIKV syndrome, including microcephaly, and severe neurological complications in adults[1,2]. Since many pathogenic viruses interfere with DC functions, this cell type is central towards viral infection outcomes They express a number of pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) that lead to the activation of the interferon (IFN) pathway and subsequent transcription of interferon-stimulated genes (ISGs) such as Viperin (virus inhibitory protein, endoplasmatic reticulum associated, IFN-inducible), MxA (Myxovirus resistance gene A), and 2′,5′-OAS (2′,5′-oligoadenylate synthase)[21,22]. It has been shown that sfRNA of DENV and WNV plays a role in inhibiting IFN responses, opening new questions on similarities with newly emerging ZIKV30,31 Severe neurological complications such as GBS and microcephaly have never been described during infections of humans with the African lineage ZIKV. The levels of sfRNA produced upon infection of MoDCs by the different ZIKV strains tested have been evaluated

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