Viruses are thought to spread across susceptible cells through an iterative process of infection, replication, and release, so that the rate of spread is limited by replication kinetics. Here, we show that vaccinia virus spreads across one cell every 75 minutes, fourfold faster than its replication cycle would permit. To explain this phenomenon, we found that newly infected cells express two surface proteins that mark cells as infected and, via exploitation of cellular machinery, induce the repulsion of superinfecting virions away toward uninfected cells. Mechanistically, early expression of proteins A33 and A36 was critical for virion repulsion and rapid spread, and cells expressing these proteins repelled exogenous virions rapidly. Additional spreading mechanisms may exist for other viruses that also spread faster than predicted by replication kinetics.Mechanisms enhancing the cell-to-cell spread of intracellular pathogens are important for virulence and are targets for development of antimicrobial therapeutics. Vaccinia virus (VACV) is a poxvirus and is the live vaccine used to eradicate smallpox (1). VACV replication is unusual in that it produces both single-and double-enveloped virions (2, 3). The single-enveloped virions, called intracellular mature virus (IMV), remain intracellular until cell lysis and spread slowly from cell to cell. In contrast, the double-enveloped virions, called cell-associated enveloped virus (CEV) and extracellular enveloped virus (EEV), are released rapidly and mediate efficient cell-to-cell spread and long-range dissemination (3, 4). VACV spreading mechanisms include virus-induced cell motility (5) and the formation of actin projections (6-8) that propel VACV particles toward other cells late during infection (9). However, we wondered whether either mechanism could explain how VACV Western Reserve (WR) spreads rapidly to form a plaque of diameter 2.90 ± 0.07 mm (SEM, nine experiments, n = 11 to 12 plaques) in 3 days (Fig. 1A). The distance between nuclei of adjacent BSC-1 cells was 37.26 ± 1.02 μm (SEM, n = 25 single cells and the 5 to 8 cells in Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts contact with it), so that VACV was spreading across each cell in <2 hours. To study this further, live video microscopy was used to measure the spread of VACV-induced cytopathic effect after infection with VACV WR (Fig. 1, B and C) or VACV expressing enhanced green fluorescent protein (EGFP) fused to core protein A5 that is expressed late during infection (vEGFPA5L) (Fig. 1, D to F, and movies S1 to S5) (10, 11). A linear increase in plaque size with time was observed (Fig. 1G), and the mean rate of spread was 32.36 ± 0.74 μm/hour (SEM, n = 9 plaques) for VACV WR. Knowing the distance between nuclei of adjacent cells, this indicated that VACV crossed one cell every 1.2 hours. This rate of spread is inconsistent with VACV replication kinetics, in which new virions are formed only 5 to 6 hours after infection (12), or virus-induced cell motility, in which ...

During the past ten years, several new hepatitis E viruses (HEVs) have been identified in various animal species. In parallel, the number of reports of autochthonous hepatitis E in Western countries has increased as well, raising the question of what role these possible animal reservoirs play in human infections. The aim of this review is to present the recent discoveries of animal HEVs and their classification within the Hepeviridae family, their zoonotic and species barrier crossing potential, and possible use as models to study hepatitis E pathogenesis. Lastly, this review describes the transmission pathways identified from animal sources.

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Hepatitis E virus (HEV) causes self-limiting acute hepatitis in humans that can eventually result in acute liver failures or progress to chronic infections. While in tropical and sub-tropical areas, HEV infections are associated with important waterborne epidemics, in Northern countries, HEV infections are autochthonous with a zoonotic origin. In the past decade, it has become clear that certain HEV genotypes are zoonotic and that swine, and more generally Suidae, are the main reservoir. Zoonotic transmissions of the virus may occur via direct contact with infected pigs, wild boars or consumption of contaminated meat. This review describes the current knowledge on domestic and wild Suidae as reservoirs of HEV and the evidence of the different routes of HEV transmission between these animals and humans.Electronic supplementary materialThe online version of this article (10.1186/s13567-017-0483-9) contains supplementary material, which is available to authorized users.

After the unexpected emergence of Bluetongue virus serotype 8 (BTV-8) in northern Europe in 2006, another arbovirus, Schmallenberg virus (SBV), emerged in Europe in 2011 causing a new economically important disease in ruminants. The virus, belonging to the Orthobunyavirus genus in the Bunyaviridae family, was first detected in Germany, in The Netherlands and in Belgium in 2011 and soon after in the United Kingdom, France, Italy, Luxembourg, Spain, Denmark and Switzerland. This review describes the current knowledge on the emergence, epidemiology, clinical signs, molecular virology and diagnosis of SBV infection.

Classical swine fever virus (CSFV) is a member of the genus Pestivirus in the family Flaviviridae. The N pro product of CSFV targets the host's innate immune response and can prevent the production of type I interferon (IFN). The mechanism by which CSFV orchestrates this inhibition was investigated and it is shown that, like the related pestivirus bovine viral diarrhea virus (BVDV), this involves the N pro protein targeting interferon regulatory factor-3 (IRF-3) for degradation by proteasomes and thus preventing IRF-3 from activating transcription from the IFN-b promoter. Like BVDV, the steady-state levels of IRF-3 mRNA are not reduced markedly by CSFV infection or N pro overexpression. Moreover, IFN-a stimulation of CSFV-infected cells induces the antiviral protein MxA, indicating that, as in BVDV-infected cells, the JAK/STAT pathway is not targeted for inhibition.

A newly developed Enzym Like Immuno Sorbant Assay (ELISA) based on the recombinant nucleocapsid protein (N) of Schmallenberg virus (SBV) was evaluated and validated for the detection of SBV-specific IgG antibodies in ruminant sera by three European Reference Laboratories. Validation data sets derived from sheep, goat and bovine sera collected in France and Germany (n = 1515) in 2011 and 2012 were categorized according to the results of a virus neutralization test (VNT) or an indirect immuno-flurorescence assay (IFA). The specificity was evaluated with 1364 sera from sheep, goat and bovine collected in France and Belgium before 2009. Overall agreement between VNT and ELISA was 98.9% and 98.3% between VNT and IFA, indicating a very good concordance between the different techniques. Although cross-reactions with other Orthobunyavirus from the Simbu serogroup viruses might occur, it is a highly sensitive, specific and robust ELISA-test validated to detect anti-SBV antibodies. This test can be applied for SBV sero-diagnostics and disease-surveillance studies in ruminant species in Europe.

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