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

  • Mingming Tan Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
  • Wenkui Sun Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
  • Chunlai Feng the Third Affiliated Hospital, Soochow University, Changzhou, China
  • Di Xia Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
  • Xiaoyue Shen Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
  • Yuan Ding Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
  • Zhicheng Liu Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
  • Zheng Xing Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
  • Xin Su Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
  • Yi Shi Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
Keywords: microRNA-let-7b, influenza virus, vaccine, mice

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.

Author Biographies

Mingming Tan, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
Department of Respiratory and critical care Medicine
Wenkui Sun, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
Department of Respiratory and critical care Medicine
Chunlai Feng, the Third Affiliated Hospital, Soochow University, Changzhou, China
Department of Respiratory Disease
Di Xia, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
Department of Respiratory and critical care Medicine
Xiaoyue Shen, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
Department of Respiratory and critical care Medicine
Yuan Ding, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
Department of Respiratory and critical care Medicine
Zhicheng Liu, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
Department of Respiratory and critical care Medicine
Zheng Xing, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
Medical School and the State Key Laboratory of Pharmaceutical Biotechnology
Xin Su, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
Department of Respiratory and critical care Medicine
Yi Shi, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
Department of Respiratory and critical care Medicine
Published
2016-09-30
How to Cite
1.
Tan M, Sun W, Feng C, Xia D, Shen X, Ding Y, Liu Z, Xing Z, Su X, Shi Y (2016) The microRNA-let-7b-mediated attenuated strain of influenza A (H1N1) virus in a mouse model. J Infect Dev Ctries 10:973-981. doi: 10.3855/jidc.6861
Section
Original Articles