Adenovirus vectored IFN-α protects mice from lethal challenge of Chikungunya virus infection

Huixin Chen; Nyo Min; Luyao Ma; Chee-Keng Mok; Justin Jang Hann Chu

doi:10.1371/journal.pntd.0008910

Adenovirus vectored IFN-α protects mice from lethal challenge of Chikungunya virus infection

PLoS Negl Trop Dis. 2020 Dec 3;14(12):e0008910. doi: 10.1371/journal.pntd.0008910. eCollection 2020 Dec.

Authors

Huixin Chen^{1

2}, Nyo Min^{1

2}, Luyao Ma^{1

2}, Chee-Keng Mok^{1

2}, Justin Jang Hann Chu^{1

2

3}

Affiliations

¹ Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
² Infectious Disease Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
³ Collaborative and Translation Unit for HFMD, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore.

Abstract

Chikungunya virus (CHIKV) is a mosquito-borne pathogen that is responsible for numerous large and geographical epidemics, causing millions of cases. However, there is no vaccine or therapeutics against CHIKV infection available. Interferon-alpha (IFN-α) has been shown to produce potent antiviral responses during viral infection. Herein we demonstrated the use of an adenovirus-vectored expressed mouse IFN-α (mDEF201) as a prophylactic and therapeutic treatment against CHIKV in vivo. 6-day-old BALB/c mice were pre- or post-treated intranasally with single dose of mDEF201 at 5 x 106 PFU per mouse and challenged with lethal dose of CHIKV. Complete survival protection was observed in mice upon a single dose of mDEF201 administration 1 days prior to virus challenge. Viral load in the serum and multiple organs were significantly reduced upon mDEF201 administration in a dose dependent manner as compare with adenovirus 5 vector placebo set. Histological analysis of the mice tissue revealed that mDEF201 could significantly reduce the tissue morphological abnormities, mainly infiltration of immune cells and muscle fibre necrosis caused by CHIKV infection. In addition, administration of mDEF201 at 6 hours post CHIKV challenge also showed promising inhibitory effect against viral replication and dissemination. In conclusion, single-dose of intranasal administration with mDEF201 as a prophylactic or therapeutic agent within 6 hours post CHIKV infection is highly protective against a lethal challenge of CHIKV in the murine model.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenoviridae*
Animals
Chikungunya Fever / therapy*
Chikungunya virus
Genetic Therapy
Genetic Vectors*
Interferon-alpha / pharmacology*
Mice
Mice, Inbred BALB C
Viral Load

Substances

Interferon-alpha

Grants and funding

This work was supported by the Ministry of Education- Singapore Tier 2 grants (MOE 2017-T2-2-014 and MOE 2017-T2-1-078) to JJHC (https://www.moe.gov.sg/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.