Intranasal Exposure to Rift Valley Fever Virus Live-Attenuated Strains Leads to High Mortality Rate in Immunocompetent Mice

Viruses. 2022 Nov 8;14(11):2470. doi: 10.3390/v14112470.

Abstract

Rift Valley fever virus (RVFV) is a pathogenic arthropod-borne virus that can cause serious illness in both ruminants and humans. The virus can be transmitted by an arthropod bite or contact with contaminated fluids or tissues. Two live-attenuated veterinary vaccines-the Smithburn (SB) and Clone 13 (Cl.13)-are currently used during epizootic events in Africa. However, their residual pathogenicity (i.e., SB) or potential of reversion (i.e., Cl.13) causes important adverse effects, strongly limiting their use in the field. In this study, we infected immunocompetent mice with SB or Cl.13 by a subcutaneous or an intranasal inoculation. Interestingly, we found that, unlike the subcutaneous infection, the intranasal inoculation led to a high mortality rate. In addition, we detected high titers and viral N antigen levels in the brain of both the SB- and Cl.13-infected mice. Overall, we unveil a clear correlation between the pathogenicity and the route of administration of both SB and Cl.13, with the intranasal inoculation leading to a stronger neurovirulence and higher mortality rate than the subcutaneous infection.

Keywords: Rift Valley fever virus; attenuated vaccine strains; intranasal exposure; pathogenicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Africa
  • Animals
  • Humans
  • Mice
  • Rift Valley Fever*
  • Rift Valley fever virus*
  • Vaccines, Attenuated / adverse effects
  • Viral Vaccines* / adverse effects

Substances

  • Viral Vaccines
  • Vaccines, Attenuated

Grants and funding

This study was funded by the Metaprogram FORESEE of the INRAe, the Ecole Pratique des Hautes Etudes, the Institut National de la Recherche pour l’agriculture, l’alimentation et l’environnement, the University of Lyon 1 and the French Government’s Investissement d’Avenir programme, Laboratoire d’Excellence “Integrative Biology of Emerging Infectious Diseases” (grant n°ANR-10-LABX-62-IBEID).