Abstract
Zika virus (ZIKV) is a neuropathic virus that causes serious neurological abnormalities such as Guillain-Barre syndrome in adults and congenital Zika syndrome (CZS) in fetuses, which makes it an important concern for global human health. A catalogue of cells that support ZIKV replication, pathogenesis, and/or the persistence of the virus still remains unknown. Here, we studied the behavior of the virus in human placenta (JEG-3) and human microglia (HMC3) cell lines in order to better understand how different host tissues respond during infection. We quantified the host transcriptional response to ZIKV infection in both types of cells at 24 and 72 h post-infection. A panel of 84 genes that are involved in the innate or adaptive immune responses was used to quantify differential expression in both cell lines. HMC3 cells showed a unique set of significant differentially expressed genes (DEGs) compared with JEG-3 cells at both time points. Subsequent analysis of these data using modern pathway analysis methods revealed that the TLR7/8 pathway was strongly inhibited in HMC3 cells, while it was activated in JEG-3 cells during virus infection. The disruption of these pathways was subsequently confirmed with specific small interfering RNA (siRNA) experiments that characterize their role in the viral life cycle, and may partially explain why ZIKV infection in placental tissue contributes to extreme neurological problems in a developing fetus.
Highlights
Zika virus (ZIKV) is an enveloped positive-sense, single-stranded RNA virus that belongs to the Flavivirus genus of the Flaviviridae family
After infecting different cell lines with ZIKV at 0.01 multiplicity of infection (MOI), we showed that ZIKV was able to replicate in both cell lines (HMC3, JEG-3) as well as in the control cells (VERO), increasing its replication along the time of infection (Figure 1A)
We evaluated the behavior of ZIKV in two target cell lines, placenta and microglia, with the aim of understanding how the virus counteracts the intracellular antiviral response in these two cell lines during infection
Summary
Zika virus (ZIKV) is an enveloped positive-sense, single-stranded RNA virus that belongs to the Flavivirus genus of the Flaviviridae family. Viruses belonging to this taxon include several human pathogens, such as yellow fever (YFV), dengue (DENV), Japanese encephalitis (JEV), tick-borne encephalitis (TBEV), and West Nile (WNV) viruses. Most ZIKV infections were associated with mild symptoms characterized by fever, rash, joint pain, and conjunctivitis. The recent worldwide epidemic has demonstrated that ZIKV can exhibit neurotropism that causes serious neurological abnormalities in humans. After a surge in microcephaly cases was associated with the recent severe Zika virus outbreak in Brazil [4], the World Health Organization declared ZIKV to be a Public
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