Pichinde Virus Infection of Outbred Hartley Guinea Pigs as a Surrogate Animal Model for Human Lassa Fever: Histopathological and Immunohistochemical Analyses.

Wun-Ju Shieh,Yuying Liang,Hinh Ly,Sherif R Zaki,Shuiyun Lan

doi:10.3390/pathogens9070579

Wun-Ju Shieh, Yuying Liang + Show 3 more

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https://doi.org/10.3390/pathogens9070579

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Abstract

Lassa virus (LASV) is a mammarenavirus (arenavirus) that causes zoonotic infection in humans that can lead to fatal hemorrhagic Lassa fever (LF) disease. Currently, there are no FDA-approved vaccines or therapeutics against LASV. Development of treatments against LF and other related arenavirus-induced hemorrhagic fevers (AHFs) requires relevant animal models that can recapitulate clinical and pathological features of AHF diseases in humans. Laboratory mice are generally resistant to LASV infection, and non-human primates, while being a good animal model for LF, are limited by their high cost. Here, we describe a small, affordable, and convenient animal model that is based on outbred Hartley guinea pigs infected with Pichinde virus (PICV), a mammarenavirus that is non-pathogenic in humans, for use as a surrogate model of human LF. We conducted a detailed analysis of tissue histopathology and immunohistochemical analysis of different organs of outbred Hartley guinea pigs infected with different PICV strains that show differential disease phenotypes and pathologies. Comparing to infection with the avirulent PICV strain (P2 or rP2), animals infected with the virulent strain (P18 or rP18) show extensive pathological changes in different organs that sustain high levels of virus replication. The similarity of tissue pathology and viral antigen distribution between the virulent PICV–guinea pig model and lethal human LASV infection supports a role of this small animal model as a surrogate model of studying human LF in order to understand its pathogenesis and for evaluating potential preventative and therapeutic options against AHFs.

Highlights

Lassa virus (LASV), the causative agent of Lassa fever (LF), was first isolated from two missionary nurses who died from LF in Nigeria in 1969 [1,2]
While disease phenotypes and viral titers of outbred Hartley guinea pigs infected with the recombinant Pichinde virus (PICV) have been reported previously [24,26], the impact of viral infection on organs and tissues has not been comprehensively characterized
We report the daily body weight and rectal temperature of all infected guinea pigs in Figure 1, which shows that the majority of both the parental

Summary

Introduction

Lassa virus (LASV), the causative agent of Lassa fever (LF), was first isolated from two missionary nurses who died from LF in Nigeria in 1969 [1,2]. LASV causes zoonotic infection in humans through ingestion of contaminated food and/or water, inhalation of tainted aerosols, or via person-to-person contact with infected body fluids [2]. New LASV infected cases each year are estimated to be up to. While the average case fatality rate of LF is ~1%, it can reach as high as 20% in hospitalized patients [2]. There are no FDA-approved vaccines or therapeutics against LASV. Development of treatments against LASV infection requires relevant animal models that can recapitulate disease and pathological features of LF and other AHFs in humans

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