Human IFITM3 restricts chikungunya virus and Mayaro virus infection and is susceptible to virus-mediated counteraction.

Interferon-induced transmembrane (IFITM) proteins restrict membrane fusion and virion internalization of several enveloped viruses. The role of IFITM proteins during alphaviral infection of human cells and viral counteraction strategies are insufficiently understood. Here, we characterized the impact of human IFITMs on the entry and spread of chikungunya virus and Mayaro virus and provide first evidence for a CHIKV-mediated antagonism of IFITMs.

Elevated Free Phosphatidylcholine Levels in Cerebrospinal Fluid Distinguish Bacterial from Viral CNS Infections.

The identification of CSF biomarkers for bacterial meningitis can potentially improve diagnosis and understanding of pathogenesis, and the differentiation from viral CNS infections is of particular clinical importance. Considering that substantial changes in CSF metabolites in CNS infections have recently been demonstrated, we compared concentrations of 188 metabolites in CSF samples from patients with bacterial meningitis ( = 32), viral meningitis/encephalitis ( = 34), and noninflamed controls ( = 66). Metabolite reprogramming in bacterial meningitis was greatest among phosphatidylcholines, and concentrations of all 54 phosphatidylcholines were significantly ( = 1.

Direct conversion of porcine primary fibroblasts into hepatocyte-like cells.

The pig is an important model organism for biomedical research, mainly due to its extensive genetic, physiological and anatomical similarities with humans. Until date, direct conversion of somatic cells into hepatocyte-like cells (iHeps) has only been achieved in rodents and human cells. Here, we employed lentiviral vectors to screen a panel of 12 hepatic transcription factors (TF) for their potential to convert porcine fibroblasts into hepatocyte-like cells.

Establishment, Validation, and Initial Application of a Sensitive LC-MS/MS Assay for Quantification of the Naturally Occurring Isomers Itaconate, Mesaconate, and Citraconate.

Itaconate is derived from the tricarboxylic acid (TCA) cycle intermediate -aconitate and links innate immunity and metabolism. Its synthesis is altered in inflammation-related disorders and it therefore has potential as clinical biomarker. Mesaconate and citraconate are naturally occurring isomers of itaconate that have been linked to metabolic disorders, but their functional relationships with itaconate are unknown.

Reverse genetics systems for contemporary isolates of respiratory syncytial virus enable rapid evaluation of antibody escape mutants.

Human respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infection in children under 5 y of age. In the absence of a safe and effective vaccine and with limited options for therapeutic interventions, uncontrolled epidemics of RSV occur annually worldwide. Existing RSV reverse genetics systems have been predominantly based on older laboratory-adapted strains such as A2 or Long.

Active equine parvovirus-hepatitis infection is most frequently detected in Austrian horses of advanced age.

Background: Equine parvovirus-hepatitis (EqPV-H) research is in its infancy. Information regarding prevalence, geographical distribution, genetic diversity, pathogenesis and risk factors enhances understanding of this potentially fatal infection.

Objectives: Determining the prevalence of EqPV-H in Austrian equids.

Anti-Infective and Antiviral Activity of Valinomycin and Its Analogues from a Sea Cucumber-Associated Bacterium, sp. SV 21.

The manuscript investigated the isolation, characterization and anti-infective potential of valinomycin (), streptodepsipeptide P11A (), streptodepsipeptide P11B (), and one novel valinomycin analogue, streptodepsipeptide SV21 (), which were all produced by the Gram-positive strain SV 21. Although the exact molecular weight and major molecular fragments were recently reported for compound , its structure elucidation was not based on compound isolation and spectroscopic techniques. We successfully isolated and elucidated the structure based on the MS fragmentation pathways as well as H and C NMR spectra and found that the previously reported structure of compound differs from our analysis.

Genetic determinants of fitness during biofilm growth.

is an environmental bacterium and an opportunistic human pathogen. It is also a well-established model organism to study bacterial adaptation to stressful conditions, such as those encountered during an infection process in the human host. Advancing knowledge on adaptation to biofilm growth conditions is bound to reveal novel strategies and targets for the treatment of chronic biofilm-associated infections.

Generation of two human ISG15 knockout iPSC clones using CRISPR/Cas9 editing.

Interferon stimulated gene 15 (ISG15) is one of the most highly upregulated proteins in response to viral infection and is involved in numerous pathways with multiple mechanisms of actions. ISG15 deficiency has been reported to induce type I interferonopathy owing to defective negative regulation of IFN-I signalling as well as enhanced antiviral protection. Here, we have generated ISG15 knockout clones from human iPSCs, which provide useful cell resources to study mechanisms of ISG15 deficiency and gain more insight into the biological function of ISG15.

Evolution of Pseudomonas aeruginosa toward higher fitness under standard laboratory conditions.

Identifying genetic factors that contribute to the evolution of adaptive phenotypes in pathogenic bacteria is key to understanding the establishment of infectious diseases. In this study, we performed mutation accumulation experiments to record the frequency of mutations and their effect on fitness in hypermutator strains of the environmental bacterium Pseudomonas aeruginosa in comparison to the host-niche-adapted Salmonella enterica. We demonstrate that P.

Targeted metabolomic profiling of cerebrospinal fluid from patients with progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML), caused by JC polyomavirus, is a demyelinating disease of the central nervous system that primarily affects oligodendrocytes. It can cause significant morbidity and mortality. An early diagnosis is of high relevance as timely immune reconstitution is essential.

Triple RNA-Seq Reveals Synergy in a Human Virus-Fungus Co-infection Model.

High-throughput RNA sequencing (RNA-seq) is routinely applied to study diverse biological processes; however, when performed separately on interacting organisms, systemic noise intrinsic to RNA extraction, library preparation, and sequencing hampers the identification of cross-species interaction nodes. Here, we develop triple RNA-seq to simultaneously detect transcriptomes of monocyte-derived dendritic cells (moDCs) infected with the frequently co-occurring pulmonary pathogens Aspergillus fumigatus and human cytomegalovirus (CMV). Comparing expression patterns after co-infection with those after single infections, our data reveal synergistic effects and mutual interferences between host responses to the two pathogens.

Liver-expressed and limit hepatitis C virus cross-species transmission to mice.

Hepatitis C virus (HCV) has no animal reservoir, infecting only humans. To investigate species barrier determinants limiting infection of rodents, murine liver complementary DNA library screening was performed, identifying transmembrane proteins Cd302 and Cr1l as potent restrictors of HCV propagation. Combined ectopic expression in human hepatoma cells impeded HCV uptake and cooperatively mediated transcriptional dysregulation of a noncanonical program of immunity genes.

Analysis of the organization and expression patterns of the convergent Pseudomonas aeruginosa lasR/rsaL gene pair uncovers mutual influence.

The two adjacent genes encoding the major Pseudomonas aeruginosa quorum-sensing regulator, LasR, and its opponent, RsaL, overlap in their coding 3' ends and produce mRNA transcripts with long untranslated 3' ends that overlap with the sense transcripts of the gene on the opposing DNA strand. In this study, we evaluated whether the overlapping genes are involved in mutual regulatory events and studied interference by natural antisense transcripts. We introduced various gene expression constructs into a P.

Mice defective in interferon signaling help distinguish between primary and secondary pathological pathways in a mouse model of neuronal forms of Gaucher disease.

Background: The type 1 interferon (IFN) response is part of the innate immune response and best known for its role in viral and bacterial infection. However, this pathway is also induced in sterile inflammation such as that which occurs in a number of neurodegenerative diseases, including neuronopathic Gaucher disease (nGD), a lysosomal storage disorder (LSD) caused by mutations in GBA.

Methods: Mice were injected with conduritol B-epoxide, an irreversible inhibitor of acid beta-glucosidase, the enzyme defective in nGD.

MicroRNA-221: A Fine Tuner and Potential Biomarker of Chronic Liver Injury.

The last decade has witnessed significant advancements in our understanding of how small noncoding RNAs, such as microRNAs (miRNAs), regulate disease progression. One such miRNA, miR-221, has been shown to play a key role in the progression of liver fibrosis, a common feature of most liver diseases. Many reports have demonstrated the upregulation of miR-221 in liver fibrosis caused by multiple etiologies such as viral infections and nonalcoholic steatohepatitis.

Cross-order host switches of hepatitis C-related viruses illustrated by a novel hepacivirus from sloths.

The genealogy of the hepatitis C virus (HCV) and the genus remains elusive despite numerous recently discovered animal hepaciviruses (HVs). Viruses from evolutionarily ancient mammals might elucidate the HV macro-evolutionary patterns. Here, we investigated sixty-seven two-toed and nine three-toed sloths from Costa Rica for HVs using molecular and serological tools.

OCIAD1 is a host mitochondrial substrate of the hepatitis C virus NS3-4A protease.

The hepatitis C virus (HCV) nonstructural protein 3-4A (NS3-4A) protease is a key component of the viral replication complex and the target of protease inhibitors used in current clinical practice. By cleaving and thereby inactivating selected host factors it also plays a role in the persistence and pathogenesis of hepatitis C. Here, we describe ovarian cancer immunoreactive antigen domain containing protein 1 (OCIAD1) as a novel cellular substrate of the HCV NS3-4A protease.

Mesenchymal to epithelial transition driven by canine distemper virus infection of canine histiocytic sarcoma cells contributes to a reduced cell motility in vitro.

Sarcomas especially of histiocytic origin often possess a poor prognosis and response to conventional therapies. Interestingly, tumours undergoing mesenchymal to epithelial transition (MET) are often associated with a favourable clinical outcome. This process is characterized by an increased expression of epithelial markers leading to a decreased invasion and metastatic rate.

Systemic Type I IFN Inflammation in Human ISG15 Deficiency Leads to Necrotizing Skin Lesions.

Most monogenic disorders have a primary clinical presentation. Inherited ISG15 deficiency, however, has manifested with two distinct presentations to date: susceptibility to mycobacterial disease and intracranial calcifications from hypomorphic interferon-II (IFN-II) production and excessive IFN-I response, respectively. Accordingly, these patients were managed for their infectious and neurologic complications.

Hepatitis E virus is effectively inactivated in platelet concentrates by ultraviolet C light.

Background And Objectives: As previous investigations have shown, THERAFLEX UV-Platelets, a UVC-based pathogen inactivation (PI) system, is effective against non-enveloped transfusion-relevant viruses such as hepatitis A virus (HAV), which are insensitive to most PI treatments for blood products. This study investigated the PI efficacy of THERAFLEX UV-Platelets against HEV in platelet concentrates (PCs).

Materials And Methods: Buffy coat-derived PCs in additive solution were spiked with cell culture-derived HEV and treated with the THERAFLEX UV-Platelets system using various doses of UVC (0·05, 0·10, 0·15 and 0·20 (standard) J/cm ).

C19orf66 is an interferon-induced inhibitor of HCV replication that restricts formation of the viral replication organelle.

Background & Aims: HCV is a positive-strand RNA virus that primarily infects human hepatocytes. Recent studies have reported that C19orf66 is expressed as an interferon (IFN)-stimulated gene; however, the intrinsic regulation of this gene within the liver as well as its antiviral effects against HCV remain elusive.

Methods: Expression of C19orf66 was quantified in both liver biopsies and primary human hepatocytes, with or without HCV infection.