1. Adenovirus vectored IFN-α protects mice from lethal challenge of Chikungunya virus infection.
- Author
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Chen, Huixin, Min, Nyo, Ma, Luyao, Mok, Chee-Keng, and Chu, Justin Jang Hann
- Subjects
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CHIKUNGUNYA virus , *VIRUS diseases , *ARBOVIRUS diseases , *ADENOVIRUS diseases , *ADENOVIRUSES , *MICE - 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. Author summary: Chikungunya has emerged as one of the most important arbovirus diseases of global health significance. Over the last decade, millions of CHIKV infections have been reported in over 80 countries across several continents. However, there is no approved vaccines or specific therapeutics available, development of antiviral strategies against CHIKV infection has become a pressing issue. In this study, the authors examined using 6-day-old BALB/c mice as an animal model to study CHIKV infection. After shown the 6-day-old mice were permissive and susceptible to CHIKV infection, the authors also evaluated the effectiveness of adenovirus-vectored mouse IFN-α (mDEF201) against systemic and lethal challenge of CHIKV infection in 6-day-old BALB/c mice. Single-dose of mDEF201 can protect mice against a lethal challenge of CHIKV. The authors believe that mDEF201 has immense clinical potential as a single dose could protect individuals at high risks during an outbreak. In addition, mDEF201 could also potentially be used to treat CHIKV infections especially during the acute phase. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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