Zika virus produces noncoding RNAs using a multi-pseudoknot structure that confounds a cellular exonuclease

ABSTRACT Vector-borne viruses pose great risks to human health. Zika virus has recently emerged as a global threat, rapidly expanding its distribution. Understanding the interactions of the virus with mosquito vectors at the molecular level is vital for devising new approaches in inhibiting virus transmission. In this study, we embarked on analyzing the transcriptional response of Aedes aegypti mosquitoes to Zika virus infection. Results showed large changes in both coding and long noncoding RNAs. Analysis of these genes showed similarities with other flaviviruses, including dengue virus, which is transmitted by the same mosquito vector. The outcomes provide a global picture of changes in the mosquito vector in response to Zika virus infection. Zika virus (ZIKV) of the Flaviviridae family is a recently emerged mosquito-borne virus that has been implicated in the surge of the number of microcephaly instances in South America. The recent rapid spread of the virus led to its declaration as a global health emergency by the World Health Organization. The virus is transmitted mainly by the mosquito Aedes aegypti, which is also the vector of dengue virus; however, little is known about the interactions of the virus with the mosquito vector. In this study, we investigated the transcriptome profiles of whole A. aegypti mosquitoes in response to ZIKV infection at 2, 7, and 14 days postinfection using transcriptome sequencing. Results showed changes in the abundance of a large number of transcripts at each time point following infection, with 18 transcripts commonly changed among the three time points. Gene ontology analysis revealed that most of the altered genes are involved in metabolic processes, cellular processes, and proteolysis. In addition, 486 long intergenic noncoding RNAs that were altered upon ZIKV infection were identified. Further, we found changes of a number of potential mRNA target genes correlating with those of altered host microRNAs. The outcomes provide a basic understanding of A. aegypti responses to ZIKV and help to determine host factors involved in replication or mosquito host antiviral response against the virus. IMPORTANCE Vector-borne viruses pose great risks to human health. Zika virus has recently emerged as a global threat, rapidly expanding its distribution. Understanding the interactions of the virus with mosquito vectors at the molecular level is vital for devising new approaches in inhibiting virus transmission. In this study, we embarked on analyzing the transcriptional response of Aedes aegypti mosquitoes to Zika virus infection. Results showed large changes in both coding and long noncoding RNAs. Analysis of these genes showed similarities with other flaviviruses, including dengue virus, which is transmitted by the same mosquito vector. The outcomes provide a global picture of changes in the mosquito vector in response to Zika virus infection.

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Exploring miRNAs as the key to understand symptoms induced by ZIKA virus infection through a collaborative database.

10.1101/042382 ◽

2016 ◽

Cited By ~ 1

Author(s):

Victor Pylro ◽

Francislon Oliveira ◽

Daniel Morais ◽

Sara Orellana ◽

Fabiano Pais ◽

...

Keyword(s):

Gene Expression ◽

Zika Virus ◽

Human Gene ◽

Noncoding Rnas ◽

World Health ◽

Translational Repression ◽

Zikv Infection ◽

Small Noncoding Rnas ◽

Congenital Zika Syndrome ◽

Health Organization

In early 2015, a ZIKA Virus (ZIKV) infection outbreak was recognized in northeast Brazil, where concerns over its possible links with infant microcephaly have been discussed. Providing a definitive link between ZIKV infection and birth defects is still a big challenge. MicroRNAs (miRNAs), are small noncoding RNAs that regulating post-transcriptional gene expression by translational repression, and play important roles in viral pathogenesis and brain development. The potential for flavivirus-mediated miRNA signaling dysfunction in brain-tissue develop provides a compelling mechanism underlying perceived linked between ZIKV and microcephaly. Here, we provide novel evidences toward to understand the mechanism in which miRNAs can be linked to the congenital ZIKA syndrome symptoms. Moreover, following World Health Organization (WHO) recommendations, we have assembled a database to help target mechanistic investigations of this possible relationship between ZIKV symptoms and miRNA mediated human gene expression, helping to foster potential targets for therapy.

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Positive Feedback Loop of Long Noncoding RNA OASL-IT1 and Innate Immune Response Restricts the Replication of Zika Virus in Epithelial A549 Cells

Journal of Innate Immunity ◽

10.1159/000513606 ◽

2021 ◽

pp. 177-191

Author(s):

Yi Wang ◽

Zhiting Huo ◽

Quanshi Lin ◽

Yuxia Lin ◽

Cancan Chen ◽

...

Keyword(s):

Viral Infection ◽

Positive Feedback ◽

Zika Virus ◽

Noncoding Rna ◽

Feedback Loop ◽

Noncoding Rnas ◽

A549 Cells ◽

Innate Immune ◽

Poly I:C ◽

Positive Feedback Loop

Expression of host noncoding RNAs and coding mRNAs is significantly altered by viral infection. In the current study, we screened the transcriptional profile of human lung epithelial A549 cells infected with Zika virus (ZIKV) by microarray assay. Seventy-nine long noncoding RNAs (lncRNAs) and 140 mRNAs were differentially expressed (DE). The bioinformatics analysis revealed that the mRNAs adjacent to the DE lncRNAs were closely related to the host responses to viral infection. We selected 7 lncRNAs from the top 50 hits for validation. The quantitative real-time PCR data confirmed that expression of selected lncRNAs was induced by ZIKV infection. Moreover, the expression of 7 lncRNAs was induced by infection of dengue virus, Japanese encephalitis virus, or vesicular stomatitis virus, or by treatment of poly(I:C) and IFN-β. Furthermore, loss of innate immune adaptor IPS-1 or receptor IFNAR1 resulted in lower induction levels of several lncRNAs by ZIKV. Overexpression of 3 lncRNAs (RPL27-OT1, OASL-IT1, and REC8-OT3) reduced the virus yields of ZIKV. Knockout of OASL-IT1 significantly enhanced ZIKV replication. In OASL-IT1 knockout cells, the levels of interferons (IFNs) and the activation of 3 innate immune signaling pathways triggered by ZIKV were dramatically reduced. Collectively, our work found a positive feedback loop in the IFN system, in which IFNs and OASL-IT1 regulate each other, thereby promoting establishment of antiviral defense.

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