Risk factors associated with the presence of hepatitis E virus in livers and seroprevalence in slaughter-age pigs: a retrospective study of 90 swine farms in France.

The frequency of sporadic cases of hepatitis E in humans in developed countries has increased in recent years. The consumption of raw or undercooked pig liver-based products has been identified as an important source of human infection. The question of possible massive human exposure to this zoonotic agent has been raised by the high prevalence of hepatitis E virus (HEV) in swine herds. However, little is known about the epidemiology of HEV on pig farms. A retrospective study, based on a previous prevalence study of 185 farms, was conducted on 90 farms located in Western France, randomly selected from this database, to identify factors associated with the presence of HEV in pig livers and HEV seroprevalence in slaughter-age pigs. At least one HEV RNA-positive liver was found in 30% of the sampled farms while seroprevalence in slaughter-age pigs at the farm level reached almost 75%. Different factors were associated with the two conditions. The risk of having HEV-positive livers was increased by early slaughter, genetic background, lack of hygiene measures and surface origin of drinking water. High HEV seroprevalence was associated with mingling practices at the nursery stage and hygiene conditions. These results can be used to determine on-farm measures to reduce within-farm HEV spread and infection of slaughter-age pigs.

Zebrafish ISG15 exerts a strong antiviral activity against RNA and DNA viruses and regulates the interferon response.

ISG15, a 15-kDa interferon-induced protein that participates in antiviral defenses of mammals, is highly conserved among vertebrates. In fish, as in mammals, viral infection and interferon treatment induce isg15 expression. The two ubiquitin-like domains of ISG15 and the presence of a consensus LRLRGG sequence in the C-terminal region, which is required for the covalent conjugation to a substrate protein, are also conserved in fish. Our data demonstrate that overexpression of zebrafish ISG15 (zf-ISG15) in EPC cells is sufficient to inhibit viral infection by RNA viruses belonging to the genera Novirhabdovirus and Birnavirus and by DNA viruses of the genus Iridovirus. In coexpression experiments with IHNV proteins, we demonstrate specific ISGylation of phosphoprotein and nonvirion protein. Mutation of the glycine residues in the consensus LRLRGG motif abolishes zf-ISG15 conjugation to these proteins and the cellular protection against viral infection, thus connecting ISGylation and ISG15-dependent viral restriction. Additionally, zf-ISG15 overexpression triggers induction of the rig-I and viperin genes as well as, to a lesser extent, the IFN gene. Overall, our data demonstrate the antiviral effect of a fish ISG15 protein, revealing the conservation among vertebrates of an ISGylation mechanism likely directed against viruses. Furthermore, our findings indicate that zf-ISG15 affects the IFN system at several levels, and its study shall shed further light on the evolution of the complex regulation of the innate antiviral response in vertebrate cells.