Sweeping analysis of transcript profile in dengue virus serotype 3 infection and antibody-dependent enhancement of infection

Virulence. 2021 Dec;12(1):2764-2776. doi: 10.1080/21505594.2021.1996072.

Abstract

Dengue virus infection mainly causes dengue hemorrhagic fever (DHF) and/or dengue shock syndrome (DSS). However, ADE (antibody-dependent enhancement) is one of the main pathogenic factors, and its pathogenic mechanism has not been fully elucidated. Recently, with the development of high-throughput sequencing, an increased number of RNAs have been confirmed to play a vital regulatory role in the process of virus infection. However, there is a lack of research on dengue virus infection and ADE. In this study, we used RNA-Seq to detect differentially expressed RNAs (DE RNAs) profiles in mock-infected, DENV-3-infected, and ADE-infected THP-1 cells. Firstly, we found 69 circRNAs, 259 miRNAs, and 18 mRNAs were differentially expressed in THP-1 vs DENV-3. In THP-1 vs ADE, 94 circRNAs, 263 miRNAs, and 111 mRNAs were differentially expressed. In DENV-3 vs ADE, 68 circRNAs, 105 miRNAs, and 94 mRNAs were differentially expressed. Functional enrichment analysis of these DE RNAs mainly focused on immune system, viral infectious diseases, cytokine-cytokine receptor interactions, and NOD/RIG-I-like receptor signaling pathways. In DENV-3 vs ADE, notably, the expression of HBB was up-regulated, which was a Fcγ Receptor-mediated phagocytosis protein. Additionally, we predicted the encoding ability of DE circRNAs, and it was found that a small peptide was encoded by novel_circ_001562 and that its amino acid sequence was consistent with that of DDX60L, which is a class of interferon-stimulated genes. Finally, we constructed the ceRNA regulatory network pathway. Therefore, our study provides a new strategy for further investigation on DENV-host interactions.

Keywords: DENV-3 (dengue virus serotype 3); ade (antibody-dependent enhancement); denv-host interactions; differentially expressed rnas (de rnas); high-throughput sequencing; immune system; interferon-stimulated genes; rna-seq; rnas expression profile; viral infectious diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody-Dependent Enhancement
  • Dengue Virus* / genetics
  • Dengue* / genetics
  • Humans
  • MicroRNAs* / genetics
  • RNA, Circular
  • RNA, Messenger / genetics
  • Serogroup

Substances

  • MicroRNAs
  • RNA, Circular
  • RNA, Messenger

Grants and funding

The study was sponsored by the National Natural Science Foundation of China (31970868); the Natural Science Foundation of Yunnan (2019ZF004); Yunnan health training project of high level talents (H-2017052);Innovation Team Project of Yunnan Science and Technology Department [202105AE160020];