Pathogenesis of Rift Valley Fever Virus in a BALB/c Mouse Model Is Affected by Virus Culture Conditions and Sex of the Animals

Victoria A. Graham, Linda Easterbrook, Emma Kennedy, Emma Rayner, Stephen Findlay-Wilson, Lucy Flett, Emma Louise Wise, Samantha Treagus, Susan Fotheringham, Sarah Kempster, Neil Almond, Stuart Dowall*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen causing disease in livestock and humans. Whilst initially restricted to the African continent, recent spread to the Arabian Peninsula has highlighted the likelihood of entry into new regions. Due to the absence of a regulatory-approved human vaccine, work is ongoing to develop and assess countermeasures. As such, small animal models play a pivotal role in providing information on disease pathogenesis and elucidating which intervention strategies confer protection. To develop and establish the BALB/c mouse model, we challenged mice with RVFV grown from two separate cell lines: one derived from mosquitoes (C6/36) and the other mammalian derived (Vero E6). Following infection, we assessed the clinical course of disease progression at days 1 and 3 post-challenge and evaluated viral tropism and immune analytes. The results demonstrated that RVFV infection was affected by the cell line used to propagate the challenge virus, with those grown in insect cells resulting in a more rapid disease progression. The lowest dose that caused uniform severe disease remained the same across both virus preparations. In addition, to demonstrate reproducibility, the lowest dose was used for a subsequent infection study using male and female animals. The results further demonstrated that male mice succumbed to infection more rapidly than their female counterparts. Our results establish an RVFV mouse model and key parameters that affect the course of disease progression in BALB/c mice.

Original languageEnglish
Article number2369
JournalViruses
Volume15
Issue number12
DOIs
Publication statusPublished - Dec 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

Keywords

  • Rift Valley fever
  • animal model
  • arbovirus
  • development
  • mosquito-borne
  • pathology
  • preclinical

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