The microRNA-let-7b-mediated attenuated strain of influenza A (H1N1) virus in a mouse model

Mingming Tan, Wenkui Sun, Chunlai Feng, Di Xia, Xiaoyue Shen, Yuan Ding, Zhicheng Liu, Zheng Xing, Xin Su, Yi Shi

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Introduction: Evaluating the attenuation of influenza viruses in animal studies is important in developing safe and effective vaccines. This study aimed to demonstrate that the microRNA (miRNA)-let-7b-mediated attenuated influenza viruses (miRT-H1N1) are sufficiently attenuated and safe in mice. Methodology: The pathogenicity of the miRT-H1N1virus was investigated in a mouse model, evaluated with median lethal dose (LD50). The replicative dynamics of the miRT-H1N1, wild type (wt)-H1N1, and scramble (scbl)-H1N1 viruses in the lungs of infected mice were compared. The degrees of lesions and the expression levels of IL-6, TNF-α, and IFN-β in the lungs of mice infected with different viruses were also analyzed. Results: In miRT-H1N1 virus-infected mice, 100% of mice survived, and a lower pathogenicity was characterized with non-significant weight loss when compared to mice infected with the control wt virus. The miRT-H1N1 virus was not fatal for mice, even at the highest dose administered. The viral load in the lungs of miRT-H1N1-infected mice was significantly lower than that of the wild-type virus-infected mice. Fewer pulmonary lesions and lower levels of selected pro-inflammatory cytokines in the lungs of the mice infected with the miRT-H1N1 virus were also observed. The virulence of the miRT-H1N1 virus reduced significantly, suggesting that the miRT-H1N1 virus was safe for mice. Conclusions: Our study demonstrated that the miRNA-mediated gene silencing is an alternative approach to attenuating the pathogenicity of wt influenza viruses that have potential in the development of influenza vaccines.

Original languageEnglish (US)
Pages (from-to)973-981
Number of pages9
JournalJournal of Infection in Developing Countries
Volume10
Issue number9
DOIs
StatePublished - Sep 2016

Keywords

  • Influenza virus
  • Mice
  • MicroRNA-let-7b
  • Vaccine

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