Journal
PLOS NEGLECTED TROPICAL DISEASES
Volume 15, Issue 1, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pntd.0008351
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Funding
- Universiti Sains Malaysia Research University Grant [1001/PBIOLOGI/811320, 1001/PBIOLOGI/8011064]
- ScienceFund Grant [305/PBIOLOGI/613238]
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This study identified and characterized lncRNAs in the genome of the Asian tiger mosquito, and found their potential involvement in DENV and ZIKV infection. Mutations in specific lncRNA loci using CRISPR-Cas9 resulted in enhanced replication of DENV and ZIKV, suggesting a role of lncRNAs in virus infection. The findings provide a foundation for further research on lncRNAs and their interaction with viruses in Asian tiger mosquitoes.
The Asian tiger mosquito, Aedes albopictus (Ae. albopictus), is an important vector that transmits arboviruses such as dengue (DENV), Zika (ZIKV) and Chikungunya virus (CHIKV). Long noncoding RNAs (lncRNAs) are known to regulate various biological processes. Knowledge on Ae. albopictus lncRNAs and their functional role in virus-host interactions are still limited. Here, we identified and characterized the lncRNAs in the genome of an arbovirus vector, Ae. albopictus, and evaluated their potential involvement in DENV and ZIKV infection. We used 148 public datasets, and identified a total of 10, 867 novel lncRNA transcripts, of which 5,809, 4,139, and 919 were intergenic, intronic and antisense respectively. The Ae. albopictus lncRNAs shared many characteristics with other species such as short length, low GC content, and low sequence conservation. RNA-sequencing of Ae. albopictus cells infected with DENV and ZIKV showed that the expression of lncRNAs was altered upon virus infection. Target prediction analysis revealed that Ae. albopictus lncRNAs may regulate the expression of genes involved in immunity and other metabolic and cellular processes. To verify the role of lncRNAs in virus infection, we generated mutations in lncRNA loci using CRISPR-Cas9, and discovered that two lncRNA loci mutations, namely XLOC_029733 (novel lncRNA transcript id: lncRNA_27639.2) and LOC115270134 (known lncRNA transcript id: XR_003899061.1) resulted in enhancement of DENV and ZIKV replication. The results presented here provide an important foundation for future studies of lncRNAs and their relationship with virus infection in Ae. albopictus. Author summary Ae. albopictus is an important vector of arboviruses such as dengue and Zika viruses. Studies on virus-host interaction at gene expression and molecular level are crucial especially in devising methods to inhibit virus replication in Aedes mosquitoes. Previous reports have shown that, besides protein-coding genes, noncoding RNAs such as lncRNAs are also involved in virus-host interaction. In this study, we report a comprehensive catalog of novel lncRNA transcripts in the genome of Ae. albopictus. We also show that the expression of lncRNAs was altered upon infection with dengue and Zika. Additionally, depletion of certain lncRNAs resulted in increased replication of dengue and Zika; hence, suggesting potential association of lncRNAs in virus infection. Results of this study provide a new avenue to the investigation of mosquito-virus interactions, especially in the aspect of noncoding genes.
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