Porcine reproductive and respiratory syndrome virus (PRRSV) infection spreads by cell-to-cell transfer in cultured MARC-145 cells, is dependent on an intact cytoskeleton, and is suppressed by drug-targeting of cell permissiveness to virus infection

BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is the etiologic agent of PRRS, causing widespread chronic infections which are largely uncontrolled by currently available vaccines or other antiviral measures. Cultured monkey kidney (MARC-145) cells provide an important tool for the study of PRRSV replication. For the present study, flow cytometric and fluorescence antibody (FA) analyses of PRRSV infection of cultured MARC-145 cells were carried out in experiments designed to clarify viral dynamics and the mechanism of viral spread. The roles of viral permissiveness and the cytoskeleton in PRRSV infection and transmission were examined in conjunction with antiviral and cytotoxic drugs. RESULTS: Flow cytometric and FA analyses of PRRSV antigen expression revealed distinct primary and secondary phases of MARC-145 cell infection. PRRSV antigen was randomly expressed in a few percent of cells during the primary phase of infection (up to about 20–22 h p.i.), but the logarithmic infection phase (days 2–3 p.i.), was characterized by secondary spread to clusters of infected cells. The formation of secondary clusters of PRRSV-infected cells preceded the development of CPE in MARC-145 cells, and both primary and secondary PRRSV infection were inhibited by colchicine and cytochalasin D, demonstrating a critical role of the cytoskeleton in viral permissiveness as well as cell-to-cell transmission from a subpopulation of cells permissive for free virus to secondary targets. Cellular expression of actin also appeared to correlate with PRRSV resistance, suggesting a second role of the actin cytoskeleton as a potential barrier to cell-to-cell transmission. PRRSV infection and cell-to-cell transmission were efficiently suppressed by interferon-γ (IFN-γ), as well as the more-potent experimental antiviral agent AK-2. CONCLUSION: The results demonstrate two distinct mechanisms of PRRSV infection: primary infection of a relatively small subpopulation of innately PRRSV-permissive cells, and secondary cell-to-cell transmission to contiguous cells which appear non-permissive to free virus. The results also indicate that an intact cytoskeleton is critical for PRRSV infection, and that viral permissiveness is a highly efficient drug target to control PRRSV infection. The data from this experimental system have important implications for the mechanisms of PRRSV persistence and pathology, as well as for a better understanding of arterivirus regulation

The United Kingdoms Eurosceptic political economy

This article explores how a political economy approach can explicate recent events in the United Kingdom’s relation to the European Union. The proposition is that neither critical nor comparative approaches do justice to the extent to which British elites have sought to differentiate the UK from the EU. The UK is here understood as a Eurosceptic political economy, constructed in opposition to European integration and, in particular, Economic and Monetary. The article explores how we have witnessed a hardening of this Eurosceptic political economy in the context of the Eurozone crisis. The most distinctive feature of which, as seen in the referendum campaign, is the extent to which the economic case for withdrawal has been established as part of the mainstream of British political debate

Beyond ‘geo-economics’: advanced unevenness and the anatomy of German austerity

This article aims to shed new light on Germany’s domineering role in the eurocrisis. I argue that the realist-inspired depiction of Germany as a ‘geo-economic power’, locked into zero-sum competition with its European partners, is built around an empty core: unable to theorise how anarchy shapes the calculus of states where security competition has receded, it cannot explain why German state managers have insisted on an austerity response to the crisis despite its significant risks and costs even for Germany itself. To unlock this puzzle, this article outlines a version of uneven and combined development (UCD) that is better able to capture the international pressures and opportunities faced by policy elites in advanced capitalist states that no longer encounter one another as direct security rivals. Applied to Germany, this lens reveals a twofold unevenness in the historical structures and growth cycles of capitalist economies that shape its contradictory choice for austerity. In the long run, the reorientation of the export-dependent German economy from Europe towards Asian and Latin American late industrialisers renders the structural adjustment of the eurozone an opportunity—from the cost-saving view of German manufacturers producing in the European home market for export abroad, as well as for German state officials keen to sustain a crumbling class compromise centred on Germany’s world market success. In the short term, however, its exposed position between the divergent post-crisis trajectories of the US and Europe accelerates pressures for austerity beyond what German state and corporate elites would otherwise consider feasible

Ukraine, Europe, and the re-routing of Globalization

The dominant Western narrative—now virtually obligatory within its media and foreign policy establishments—asserts that Vladimir Putin’s invasion of Ukraine on 24 February 2022 was unprovoked, deriving from domestic political imperatives and messianic imperial nostalgia. Yet, while these factors must be included within a comprehensive causal argument, a deeper and more satisfactory explanation for the invasion situates the predicament of the Russian ruling class—and thus government—within the context of the systematic, decades-long project of NATO expansion and a series of specific provocative actions and decisions taken by Kyiv and Washington in the second half of 2021. The United States has consistently opposed integration between Russia and Western Europe. The key parameter of U.S. neo-imperial strategy in Europe-Asia remains embedded in Cold War geo-politics, namely that U.S. hegemony in Eurasia rests on the exclusion of Russia from European affairs and the prevention of a geo-economic axis between Berlin, Moscow and Beijing. However, even as the war may result in a final settling of accounts in the U.S.-Russia relationship and beyond, it has also thrown into increasingly sharp relief the growing conflict of class interests and complex geopolitical asymmetries and contradictions in the transatlantic relationship

Immune response to lactate dehydrogenase-elevating virus: serologically specific rabbit neutralizing antibody to the virus.

A rabbit was immunized with large amounts of the lactate dehydrogenase-elevating virus (LDV) over a 9-month period. The plasma from this rabbit possessed an anti-LDV IgG titer of 1:80,000 as measured by the enzyme-linked immunosorbent assay (ELISA) method and a neutralizing titer of 1:1,000 for the homologous strain of LDV. LDV neutralization at 4 degrees C followed single-hit kinetics. In contrast, mouse anti-LDV IgG in plasma of chronically LDV-infected mice failed to neutralize LDV at 4 degrees C and neutralization at 37 degrees C was slow, biphasic, and inefficient compared with the neutralization caused by rabbit anti-LDV IgG, even though high levels of anti-LDV IgG were detectable in mouse plasma by the ELISA method. Rabbit anti-LDV IgG neutralized one heterologous strain of LDV as rapidly as it did the homologous strain, but failed to significantly neutralize five other strains of LDV, all of which were originally isolated from different mouse strains bearing transplantable tumors. The results indicate clear serological differences between LDV strains. Cross-reactions between the strains, however, were observed by ELISA, using the antibody induced during persistent infection of mice with each LDV strain. Immunoglobulin M (IgM) from mice infected for 15 days with the various strains bound equally to our LDV strain. IgG obtained from 2-month-infected mice also cross-reacted, but to a varying extent which partly correlated with the specificity detected by neutralization. Both rabbit and mouse anti-LDV IgG enhanced the infectivity of LDV at a low multiplicity of infection for primary cultures of peritoneal mouse macrophages