Efficient Human Cytomegalovirus Replication in Primary Endothelial Cells Is SOCS3 Dependent.

Background: In immunocompromised patients, human cytomegalovirus (HCMV) infection is a major cause of morbidity and mortality. Suppressor of cytokine signaling (SOCS) proteins are very potent negative regulators of the janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways. We hypothesized that HCMV exploits SOCS1 and/or SOCS3 to its advantage.

Statins demonstrate a broad anti-cytomegalovirus activity in vitro in ganciclovir-susceptible and resistant strains.

Vasculoprotective and cholesterol-lowering properties are hallmarks of statins. Recently, statins have been found to exhibit antiviral activity. Little is known about the potential of statins against human cytomegalovirus (HCMV), a risk factor in the pathogenesis of atherosclerosis.

Entry of human cytomegalovirus into porcine endothelial cells depends on both the cellular vascular origin and the viral strain.

Background: Primary infection and reactivation of human cytomegalovirus (HCMV) is associated with allograft rejection. Pig-to-human xenotransplantation is regarded as an alternative to circumvent donor organ shortage and inevitably, porcine endothelial cells (pEC) will be exposed to human pathogens, among them HCMV. Infection of pEC with HCMV induces apoptosis and entry is sufficient to induce phenotypic alterations, which have the potential to result in rejection and vasculopathy.

Brief Exercise Increases Peripheral Blood NK Cell Counts without Immediate Functional Changes, but Impairs their Responses to ex vivo Stimulation.

Physical as well as psychological stress increases the number of circulating peripheral blood NK cells. Whereas some studies found a positive correlation between exercise and NK cell counts and cytotoxic activity, others showed that, for example, heavy training leads to a decrease in per cell NK cytotoxicity. Thus, the impact of exercise on NK cell function and eventually on altered immunocompetence remains to be elucidated.

The microtubule stabilizer patupilone counteracts ionizing radiation-induced matrix metalloproteinase activity and tumor cell invasion.

Background: Ionizing radiation (IR) in combination with microtubule stabilizing agents (MSA) is a promising combined treatment modality. Supra-additive treatment responses might result from direct tumor cell killing and cooperative indirect, tumor cell-mediated effects on the tumor microenvironment. Here we investigated deregulation of matrix metalloproteinase (MMP) activity, as an important component of the tumor microenvironment, by the combined treatment modality of IR with the clinically relevant MSA patupilone.

Complete absence of the αGal xenoantigen and isoglobotrihexosylceramide in α1,3galactosyltransferase knock-out pigs.

Background: Anti-Galα1,3Galβ-R natural antibodies are responsible for hyperacute rejection in pig-to-primate xenotransplantation. Although the generation of pigs lacking the α1,3galactosyltransferase (GalT) has overcome hyperacute rejection, antibody-mediated rejection is still a problem. It is possible that other enzymes synthesize antigens similar to Galα1,3Gal epitopes that are recognized by xenoreactive antibodies.

Efficiency of porcine endothelial cell infection with human cytomegalovirus depends on both virus tropism and endothelial cell vascular origin.

Background: Human cytomegalovirus (HCMV) infection or reactivation has been linked to allograft rejection resulting from endothelial injury and immune activation. In pig-to-human xenotransplantation, currently investigated to circumvent the shortage of human organs in transplantation medicine, the porcine endothelium will inevitably be exposed to human pathogens such as HCMV. We investigated the susceptibility of porcine endothelial cells (pEC) to HCMV infection.

Inhibition of direct and indirect TLR-mediated activation of human NK cells by low molecular weight dextran sulfate.

NK cells express toll-like receptors (TLR) that recognize conserved pathogen or damage associated molecular patterns and play a fundamental role in innate immunity. Low molecular weight dextran sulfate (DXS), known to inhibit the complement system, has recently been reported by us to inhibit TLR4-induced maturation of human monocyte-derived dendritic cells (MoDC). In this study, we investigated the capability of DXS to interfere with human NK cell activation triggered directly by TLR2 agonists or indirectly by supernatants of TLR4-activated MoDC.

Can human viruses infect porcine xenografts?

Xenotransplantation exposes the recipient to known and unknown pathogens of the donor pig (donor-derived xenosis). A major effort has been undertaken to minimize the risk of transmission from the donor using specialized breeding techniques. With the exception of endogenous retroviruses and porcine lymphotropic herpesvirus, exclusion of known pathogens was successful and has eliminated a majority of donor pathogens.

Critical issues related to porcine xenograft exposure to human viruses: lessons from allotransplantation.

Purpose Of Review: Xenotransplantation of tissues from swine into humans poses the threat of bidirectional transfer of porcine or human microorganisms to the recipient or to the xenograft, respectively. This review focuses on recipient-derived infection. Recent data are reviewed that assess the susceptibility of porcine cells to human viruses.

Human CMV infection of porcine endothelial cells increases adhesion receptor expression and human leukocyte recruitment.

Background: Potential xenozoonosis is a concern for the clinical application of xenotransplantation. Human cytomegalovirus (HCMV) is one of the most important pathogens in allotransplantation, but the consequences of HCMV cross-species infection of porcine xenografts are unknown. Therefore, we investigated the effects of HCMV infection of porcine endothelial cells (pEC) on cell surface molecule expression and human leukocyte recruitment.