Maporal Hantavirus Causes Mild Pathology in Deer Mice (Peromyscus maniculatus).

Amanda Mcguire,Tawfik Aboellail,Amber Rico,Sandra L Quackenbush,Joseph R Fauver,Kaitlyn Miedema,Ann Hawkinson,Tony Schountz

doi:10.3390/v8100286

Amanda Mcguire, Tawfik Aboellail + Show 6 more

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https://doi.org/10.3390/v8100286

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Abstract

Rodent-borne hantaviruses can cause two human diseases with many pathological similarities: hantavirus cardiopulmonary syndrome (HCPS) in the western hemisphere and hemorrhagic fever with renal syndrome in the eastern hemisphere. Each virus is hosted by specific reservoir species without conspicuous disease. HCPS-causing hantaviruses require animal biosafety level-4 (ABSL-4) containment, which substantially limits experimental research of interactions between the viruses and their reservoir hosts. Maporal virus (MAPV) is a South American hantavirus not known to cause disease in humans, thus it can be manipulated under ABSL-3 conditions. The aim of this study was to develop an ABSL-3 hantavirus infection model using the deer mouse (Peromyscus maniculatus), the natural reservoir host of Sin Nombre virus (SNV), and a virus that is pathogenic in another animal model to examine immune response of a reservoir host species. Deer mice were inoculated with MAPV, and viral RNA was detected in several organs of all deer mice during the 56 day experiment. Infected animals generated both nucleocapsid-specific and neutralizing antibodies. Histopathological lesions were minimal to mild with the peak of the lesions detected at 7–14 days postinfection, mainly in the lungs, heart, and liver. Low to modest levels of cytokine gene expression were detected in spleens and lungs of infected deer mice, and deer mouse primary pulmonary cells generated with endothelial cell growth factors were susceptible to MAPV with viral RNA accumulating in the cellular fraction compared to infected Vero cells. Most features resembled that of SNV infection of deer mice, suggesting this model may be an ABSL-3 surrogate for studying the host response of a New World hantavirus reservoir.

Highlights

Hantaviruses are negative-stranded, trisegmented members of the Bunyaviridae family that are hosted by rodents, insectivores, or bats [1,2]
ELISA specific for nucleocapsid antigen showed that one deer mouse had seroconverted on day 14, as had both deer mice euthanized on day 56 (Figure 1b)
Several reservoir host infection models have been developed for studying pathogenic hantavirus infections; Old World Seoul virus infection of Norway rats (Rattus norvegicus) and Puumala virus infection of bank voles (Myodes glareolus), and two New World viruses, Black Creek Canal virus infection of cotton rats (Sigmodon hispidus) and Sin Nombre virus (SNV) infection of deer mice [16,32,33,34,35]

Summary

Introduction

Hantaviruses are negative-stranded, trisegmented members of the Bunyaviridae family that are hosted by rodents, insectivores, or bats [1,2]. All of which are hosted by rodents, can cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia, or hantavirus cardiopulmonary syndrome (HCPS) in the Americas [3,4]. The principal cellular target of hantaviruses are vascular endothelial cells but without conspicuous effects on those cells, vascular leakage is a prominent feature of hantavirus disease [12]. Deer mice (Peromyscus maniculatus) are the principal reservoir hosts of Sin Nombre virus (SNV) [13,14,15], the etiologic agent of most HCPS cases in North America [1,4]. Immune markers suggest a subtle Th1/Th2 response, followed by signatures of regulatory T cell responses that may impair cytotoxic T cell activities and contribute to persistent infection [18,19,20]

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