MicroRNA and mRNA Dysregulation in Astrocytes Infected with Zika Virus

Abstract

The Zika virus (ZIKV) epidemic is an ongoing public health concern. ZIKV is a flavivirus reported to be associated with microcephaly, and recent work in animal models demonstrates the ability of the virus to cross the placenta and affect fetal brain development. Recent findings suggest that the virus preferentially infects neural stem cells and thereby deregulates gene expression, cell cycle progression, and increases cell death. However, neuronal stem cells are not the only brain cells that are susceptible to ZIKV and infection of other brain cells may contribute to disease progression. Herein, we characterized ZIKV replication in astrocytes, and profiled temporal changes in host microRNAs (miRNAs) and transcriptomes during infection. We observed the deregulation of numerous processes known to be involved in flavivirus infection, including genes involved in the unfolded protein response pathway. Moreover, a number of miRNAs were upregulated, including miR-30e-3p, miR-30e-5p, and, miR-17-5p, which have been associated with other flavivirus infections. This study highlights potential miRNAs that may be of importance in ZIKV pathogenesis.

Zika virus infection induces RNAi-mediated antiviral immunity in human neural progenitors and brain organoids

“…Previous studies failed to detect any ZIKV-specific vsiRNAs in astrocytes, 44 therefore we tested whether human neurons differentiated from hNPCs retained the capability of cleaving viral dsRNA into vsiRNAs. vsRNAs detected in ZIKV-infected neurons were predominantly nonspecific viral RNA degradation products, with a random size distribution and an overwhelming bias for positive strands (Supplementary information, Fig.…”

São Paulo School of Advanced Sciences on Vaccines: an overview

“…Radial-glia cells were shown to facilitate brain infection and damage in babies through their contact with the virus via Axl and its ligand, Gas6 [49]. Subsequently, the ZIKV suppresses the interferon response in the central nervous system (CNS), modulating apoptosis and autophagy-related genes [50]. Moreover, different mutation patterns of ZIKV particles were related to distinct alterations found in mouse brains depending on the challenged strain (BALB/c and C578/6J).…”

Zika virus: Molecular responses and tissue tropism in the mammalian host

“…Further investigation led to the discovery of several upregulated miRNA in these cells 24 hpi, some of which were involved in inhibition of viral processes, inhibition of host cell cycle, and downregulation of innate immune responses. In addition, at 24 hpi, several signaling pathways were enriched in these cells, such as the p53 signaling pathway, Ephrin B signaling and the unfolded response protein pathway . The antiviral response in the astrocytes was modest, and the genes like TLR3 and IL1β were downregulated after a transient increase in expression because of the infection .…”

“…In addition, at 24 hpi, several signaling pathways were enriched in these cells, such as the p53 signaling pathway, Ephrin B signaling and the unfolded response protein pathway . The antiviral response in the astrocytes was modest, and the genes like TLR3 and IL1β were downregulated after a transient increase in expression because of the infection . The transcripts of the DICER protein complex were reduced at 72 hpi, which in turn globally shut down the production of miRNA, supposedly enhancing the process of viral RNA replication within the astrocytes …”