N-acetylcysteine lacks universal inhibitory activity against influenza A viruses

N-acetylcysteine (NAC) has been recently proposed as an adjuvant therapeutic drug for influenza pneumonia in humans. This proposal is based on its ability to restrict influenza virus replication in vitro and to attenuate the severity of the disease in mouse models. Although available studies were made with different viruses (human and avian), published information related to the anti-influenza spectrum of NAC is scarce. In this study, we show that NAC is unable to alter the course of a fatal influenza pneumonia caused by inoculation of a murinized swine H1N1 influenza virus. NAC was indeed able to inhibit the swine virus in vitro but far less than reported for other strains. Therefore, susceptibility of influenza viruses to NAC appears to be strain-dependent, suggesting that it cannot be considered as a universal treatment for influenza pneumonia

Schmallenberg virus pathogenesis, tropism and interaction with the innate immune system of the host

Schmallenberg virus (SBV) is an emerging orthobunyavirus of ruminants associated with outbreaks of congenital malformations in aborted and stillborn animals. Since its discovery in November 2011, SBV has spread very rapidly to many European countries. Here, we developed molecular and serological tools, and an experimental in vivo model as a platform to study SBV pathogenesis, tropism and virus-host cell interactions. Using a synthetic biology approach, we developed a reverse genetics system for the rapid rescue and genetic manipulation of SBV. We showed that SBV has a wide tropism in cell culture and “synthetic” SBV replicates in vitro as efficiently as wild type virus. We developed an experimental mouse model to study SBV infection and showed that this virus replicates abundantly in neurons where it causes cerebral malacia and vacuolation of the cerebral cortex. These virus-induced acute lesions are useful in understanding the progression from vacuolation to porencephaly and extensive tissue destruction, often observed in aborted lambs and calves in naturally occurring Schmallenberg cases. Indeed, we detected high levels of SBV antigens in the neurons of the gray matter of brain and spinal cord of naturally affected lambs and calves, suggesting that muscular hypoplasia observed in SBV-infected lambs is mostly secondary to central nervous system damage. Finally, we investigated the molecular determinants of SBV virulence. Interestingly, we found a biological SBV clone that after passage in cell culture displays increased virulence in mice. We also found that a SBV deletion mutant of the non-structural NSs protein (SBVΔNSs) is less virulent in mice than wild type SBV. Attenuation of SBV virulence depends on the inability of SBVΔNSs to block IFN synthesis in virus infected cells. In conclusion, this work provides a useful experimental framework to study the biology and pathogenesis of SBV

Acute Respiratory Distress Syndrome Induced by a Swine 2009 H1N1 Variant in Mice

Background: Acute respiratory distress syndrome (ARDS) induced by pandemic 2009 H1N1 influenza virus has been widely reported and was considered the main cause of death in critically ill patients with 2009 H1N1 infection. However, no animal model has been developed for ARDS caused by infection with 2009 H1N1 virus. Here, we present a mouse model of ARDS induced by 2009 H1N1 virus. Methodology Principal Findings: Mice were inoculated with A/swine/Shandong/731/2009 (SD/09), which was a 2009 H1N1 influenza variant with a G222D mutation in the hemagglutinin. Clinical symptoms were recorded every day. Lung injury was assessed by lung water content and histopathological observation. Arterial blood gas, leukocyte count in the bronchial alveolar lavage fluid and blood, virus titers, and cytokine levels in the lung were measured at various times post-inoculation. Mice infected with SD/09 virus showed typical ARDS symptoms characterized by 60 % lethality on days 8–10 postinoculation, highly edematous lungs, inflammatory cellular infiltration, alveolar and interstitial edema, lung hemorrhage, progressive and severe hypoxemia, and elevated levels of proinflammatory cytokines and chemokines. Conclusions/Significance: These results suggested that we successfully established an ARDS mouse model induced by a virulent 2009 H1N1 variant without previous adaptation, which may be of benefit for evaluating the pathogenesis or therapy of human ARDS caused by 2009 H1N1 virus

Application of integrated production and economic models to estimate the impact of Schmallenberg virus for various beef suckler production systems in France and the United Kingdom

Background: Schmallenberg virus (SBV) was first detected in November 2011 in Germany and then rapidly spread throughout Europe. In beef suckler farms, clinical signs are mainly associated with reproductive disorders, particularly in late gestation, and intransient and non-specific symptoms, namely diarrhea, inappetence and fever. The objectives of this study were to develop models that simulate the production of different beef suckler systems in the United Kingdom (UK) and France and to use these models to estimate, through partial budget analyses, the farm-level economic cost of SBV under two disease impact scenarios, namely high and low impact. The probability for a farm to be in the high or low scenario depends, among other, on the high, low or nil vectorial activity for a given period and location and on the period(s) of sensitivity of the animals to the disease. Results: Under the high impact scenario, the estimated SBV impact ranged from 26 is an element of to 43 is an element of per cow per year in France and from 29 is an element of to 36 is an element of per cow per year in the UK. It was approximately half of this amount in the low impact scenario. These financial impacts represent 5 to 16% of the gross margin, depending on the country, impact scenario and livestock system considered. Most of the SBV impact originates from the costs of the steers and heifers not produced. Differences identified between the systems studied mainly stem from differences among the value of the steers or heifers sold: SBV impact is higher for British autumn calving systems compared to spring calving, and for French farms with calving and fattening activities compared to farms with only a single, annual calving activity. Conclusions: This study shows the usefulness of integrated production and economic models to accurately evaluate the costs of diseases and understand which factors have major impacts in the different systems. The models stand as a useful basis for animal health professionals when considering alternative disease control measures. They are also a farm accounting tool for estimating disease impact on differing production practices, which creates the necessary basis for cost-effectiveness analysis of intervention strategies, such as vaccination