Encephalomyocarditis virus may use different pathways to initiateinfection of primary human cardiomyocytes

Encephalomyocarditis virus (EMCV) caninfect a wide range of vertebrate species including swineand non-human primates, but few data are available forhumans. We therefore wanted to gain further insight intothe mechanisms involved in EMCV infection of humancells. For this purpose, we analyzed the permissiveness ofprimary human cardiomyocytes towards two strains ofEMCV; a pig myocardial strain (B279/95) and a rat strain(1086C). In this study, we show that both strains productivelyinfect primary human cardiomyocytes and inducecomplete cytolysis. Binding and infection inhibitionexperiments indicated that attachment and infection areindependent of sialic acid and heparan sulfate for B279/95and dependent for 1086C. Sequence comparison betweenthe two strains and three-dimensional analysis of the capsidrevealed that six of the seven variable residues are surfaceexposed,suggesting a role for these amino acids in binding.Moreover, analysis of variants isolated from the 1086Cstrain revealed the importance of lysine 231 of VP1 in theattachment of EMCV to cell-surface sialic acid residues.Together, these results show a potential for EMCV strainsto use at least two different binding possibilities to initiateinfection and provide new insights into the mechanismsinvolved in primary human cell recognition by EMCV

Role of lysophosphatidic acid receptor LPA2 in the development of allergic airway inflammation in a murine model of asthma

<p>Abstract</p> <p>Background</p> <p>Lysophosphatidic acid (LPA) plays a critical role in airway inflammation through G protein-coupled LPA receptors (LPA_1-3). We have demonstrated that LPA induced cytokine and lipid mediator release in human bronchial epithelial cells. Here we provide evidence for the role of LPA and LPA receptors in Th2-dominant airway inflammation.</p> <p>Methods</p> <p/> <p>Wild type, LPA₁heterozygous knockout mice (LPA₁^+/-), and LPA₂heterozygous knockout mice (LPA₂^+/-) were sensitized with inactivated <it>Schistosoma mansoni </it>eggs and local antigenic challenge with <it>Schistosoma mansoni </it>soluble egg Ag (SEA) in the lungs. Bronchoalveolar larvage (BAL) fluids and lung tissues were collected for analysis of inflammatory responses. Further, tracheal epithelial cells were isolated and challenged with LPA.</p> <p>Results</p> <p>BAL fluids from <it>Schistosoma mansoni </it>egg-sensitized and challenged wild type mice (4 days of challenge) showed increase of LPA level (~2.8 fold), compared to control mice. LPA₂^+/-mice, but not LPA₁^+/-mice, exposed to <it>Schistosoma mansoni </it>egg revealed significantly reduced cell numbers and eosinophils in BAL fluids, compared to challenged wild type mice. Both LPA₂^+/-and LPA₁^+/-mice showed decreases in bronchial goblet cells. LPA₂^+/-mice, but not LPA₁^+/-mice showed the decreases in prostaglandin E2 (PGE2) and LPA levels in BAL fluids after SEA challenge. The PGE2 production by LPA was reduced in isolated tracheal epithelial cells from LPA₂^+/-mice. These results suggest that LPA and LPA receptors are involved in <it>Schistosoma mansoni </it>egg-mediated inflammation and further studies are proposed to understand the role of LPA and LPA receptors in the inflammatory process.</p