Evaluation of a novel severe combined immunodeficiency mouse model for antiviral drug evaluation against Chandipura virus infection

• Published in: Antiviral research Vol. 213; p. 105582
• Main Authors: Kitaura, Satoshi, Tobiume, Minoru, Kawahara, Madoka, Satoh, Masaaki, Kato, Hirofumi, Nakayama, Noriko, Nakajima, Nozomi, Komeno, Takashi, Furuta, Yousuke, Suzuki, Tadaki, Moriya, Kyoji, Saijo, Masayuki, Ebihara, Hideki, Takayama-Ito, Mutsuyo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2023
• Subjects: Animals; Antiviral Agents - therapeutic use; Child; CHPV; Drug Evaluation; Encephalitis; Favipiravir; Humans; Mice; Mice, SCID; Pediatric infectious disease; SCID; Severe Combined Immunodeficiency - drug therapy; T-705; Vesiculovirus; Vesiculovirus - genetics; Pediatric infectious disease; Vesiculovirus; CHPV; SCID; Favipiravir; T-705
• ISSN: 0166-3542; 1872-9096; 1872-9096
• DOI: 10.1016/j.antiviral.2023.105582

Chandipura virus (CHPV) is a negative-sense single-stranded RNA virus known to cause fatal encephalitis outbreaks in the Indian subcontinent. The virus displays tropism towards the pediatric population and holds significant public health concerns. Currently, there is no specific, effective therapy for CHPV encephalitis. In this study, we evaluated a novel C.B-17 severe combined immunodeficiency (SCID) mouse model which can be used for pre-clinical antiviral evaluation. Inoculation of CHPV developed a lethal infection in our model. Plaque assay and immunohistochemistry detected increased viral loads and antigens in various organs, including the brain, spinal cord, adrenal glands, and whole blood. We further conducted a proof-of-concept evaluation of favipiravir in the SCID mouse model. Favipiravir treatment improved survival with pre-symptomatic (days 5–14) and post-symptomatic (days 9–18) treatment. Reduced viral loads were observed in whole blood, kidney/adrenal gland, and brain tissue with favipiravir treatment. The findings in this study demonstrate the utility of SCID mouse for in vivo drug efficacy evaluation and the potential efficacy of favipiravir against CHPV infection. [Display omitted] •Chandipura virus causes a lethal infection in severe combined immunodeficiency mice.•Favipiravir treatment improved survival in the novel mouse model.•The novel mouse model has utility in antiviral evaluation against Chandipura virus.