Choice of inbred rat strain impacts lethality and disease course after respiratory infection with Rift Valley Fever Virus.

Jacquelyn M Bales,Douglas S Reed,Laura M Bethel,Diana S Powell,Amy L Hartman

doi:10.3389/fcimb.2012.00105

Jacquelyn M Bales, Douglas S Reed + Show 3 more

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https://doi.org/10.3389/fcimb.2012.00105

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Abstract

Humans infected with Rift Valley Fever Virus (RVFV) generally recover after a febrile illness; however, a proportion of patients progress to a more severe clinical outcome such as hemorrhagic fever or meningoencephalitis. RVFV is naturally transmitted to livestock and humans by mosquito bites, but it is also infectious through inhalational exposure, making it a potential bioterror weapon. To better understand the disease caused by inhalation of RVFV, Wistar-Furth, ACI, or Lewis rats were exposed to experimental aerosols containing virulent RVFV. Wistar-Furth rats developed a rapidly progressing lethal hepatic disease after inhalational exposure; ACI rats were 100-fold less susceptible and developed fatal encephalitis after infection. Lewis rats, which do not succumb to parenteral inoculation with RVFV, developed fatal encephalitis after aerosol infection. RVFV was found in the liver, lung, spleen, heart, kidney and brain of Wistar Furth rats that succumbed after aerosol exposure. In contrast, RVFV was found only in the brains of ACI or Lewis rats that succumbed after aerosol exposure. Lewis rats that survived s.c. infection were not protected against subsequent re-challenge by aerosol exposure to the homologous virus. This is the first side-by-side comparison of the lethality and pathogenesis of RVFV in three rat strains after aerosol exposure and the first step toward developing a rodent model suitable for use under the FDA Animal Rule to test potential vaccines and therapeutics for aerosol exposure to RVFV.

Highlights

Rift Valley Fever Virus (RVFV), a mosquito-borne member of the Bunyaviridae family of segmented negative sense RNA viruses, causes large explosive epidemics of severe disease in livestock that have significant economic impact in Africa and the Arabian Peninsula
While it is thought that the primary route of transmission of RVFV in natural outbreaks is by mosquito vectors, RVFV can be infectious and virulent when inhaled by humans (Francis and Magill, 1935; Smithburn et al, 1949; Hoogstraal et al, 1979) or experimental animals (Miller et al, 1963; Anderson et al, 1991a; Morrill and Peters, 2011)
medical countermeasures (MCMs) that can protect against RVFV, after aerosol exposure, are urgently needed

Summary

Introduction

Rift Valley Fever Virus (RVFV), a mosquito-borne member of the Bunyaviridae family of segmented negative sense RNA viruses, causes large explosive epidemics of severe disease in livestock that have significant economic impact in Africa and the Arabian Peninsula. While RVFV is transmissible to humans by mosquito bite, the virus spreads rapidly by mucosal and aerosol infection caused by humans handling infected animal carcasses (Hoogstraal et al, 1979; Madani et al, 2003; Mohamed et al, 2010). Human infections with RVFV begin with a short incubation period followed by a significant fever, headache, myalgia, anorexia, and, in some cases, nausea and vomiting (Easterday, 1965; Laughlin et al, 1979). Given the large number of humans infected during the known outbreaks, a significant number of individuals can be hospitalized. While it is thought that the primary route of transmission of RVFV in natural outbreaks is by mosquito vectors, RVFV can be infectious and virulent when inhaled by humans (Francis and Magill, 1935; Smithburn et al, 1949; Hoogstraal et al, 1979) or experimental animals (Miller et al, 1963; Anderson et al, 1991a; Morrill and Peters, 2011)

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