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Distinct Pathological Changes in Preweaning Mice Infected with Live-Attenuated Rift Valley Fever Virus Strains.

Cigdem Alkan¹, Eduardo Jurado-Cobena², Tetsuro Ikegami^1,3,4

¹Department of Pathology, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.

|July 27, 2024

Summary

This study evaluated three live-attenuated Rift Valley fever virus (RVFV) vaccine strains in young mice. The ∆NSs-∆NSm-rZH501 strain showed more brain inflammation compared to rMP-12 and RVax-1.

Keywords:

MP-12 RVax-1 Rift Valley fever age dependent encephalitis hepatitis live-attenuated vaccine mouse preweaning ∆NSs-∆NSm-rZH501

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Area of Science:

Veterinary Virology
Immunology
Pathology

Background:

Rift Valley fever (RVF) is a significant zoonotic disease transmitted by mosquitoes.
Live-attenuated vaccines are crucial for RVF control in animals and humans.
Assessing vaccine safety and virulence is essential for RVF vaccine development.

Purpose of the Study:

To characterize the relative virulence of three live-attenuated RVF vaccine strains: rMP-12, RVax-1, and ∆NSs-∆NSm-rZH501.
To evaluate the utility of a preweaning mouse model for assessing RVF vaccine virulence.

Main Methods:

Infection of 19-day-old inbred C57BL/6 mice with three live-attenuated RVF vaccine strains.
Histopathological examination of mouse brains to assess viral pathogenesis and inflammatory responses.

Main Results:

The mouse model did not demonstrate dose-dependent pathogenesis.
Mice infected with ∆NSs-∆NSm-rZH501 exhibited inflammatory cell infiltration around infected neurons and focal lesions.
Mice infected with rMP-12 or RVax-1 showed diffuse viral spread with minimal brain inflammation.

Conclusions:

The preweaning mouse model can reveal distinct host responses to attenuated RVFV strains.
Further refinement of the model may be needed for quantitative virulence assessment.
∆NSs-∆NSm-rZH501 demonstrated a different neuropathogenesis profile compared to rMP-12 and RVax-1.