Equine Torovirus (BEV) Induces Caspase-Mediated Apoptosis in Infected Cells

Ana M Maestre,Dolores Rodríguez,Ana Garzón,Eliane F Meurs

doi:10.1371/journal.pone.0020972

Abstract

Toroviruses are gastroenteritis causing agents that infect different animal species and humans. To date, very little is known about how toroviruses cause disease. Here, we describe for the first time that the prototype member of this genus, the equine torovirus Berne virus (BEV), induces apoptosis in infected cells at late times postinfection. Observation of BEV infected cells by electron microscopy revealed that by 24 hours postinfection some cells exhibited morphological characteristics of apoptotic cells. Based on this finding, we analyzed several apoptotic markers, and observed protein synthesis inhibition, rRNA and DNA degradation, nuclear fragmentation, caspase-mediated cleavage of PARP and eIF4GI, and PKR and eIF2α phosphorylation, all these processes taking place after peak virus production. We also determined that both cell death receptor and mitochondrial pathways are involved in the apoptosis process induced by BEV. BEV-induced apoptosis at late times postinfection, once viral progeny are produced, could facilitate viral dissemination in vivo and contribute to viral pathogenesis.

Highlights

Toroviruses are enteric viruses which infect different animal species and humans and cause diarrhea
Derm cells infected with Berne virus (BEV) at a multiplicity of infection of 5 pfu/cell, the first signs of infection could be detected by about 24 hpi, and cytopathic effect (CPE) was seen in some cells
The number of cells showing this morphology readily increases with the time postinfection, in agreement with the CPE observed by phase-contrast microscopy

Summary

Introduction

Toroviruses are enteric (and probably respiratory) viruses which infect different animal species and humans and cause diarrhea. There are four torovirus species recognized by the ICTV, established according to the animal host that they infect: bovine torovirus (BToV), porcine torovirus (PToV), human torovirus (HToV) and equine torovirus (EToV) (ICTV web site: www.ictvonline.org). The latter virus was the first torovirus identified, isolated in 1972 from the faeces of a horse in Berne (Switzerland), and named Berne virus or BEV [3]. The propagation of different BToV strains in the human HRT-18 cell line has been recently described [4,5]

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