A case of persistent human pegivirus infection in two separate pregnancies of a woman

Human pegivirus (HPgV) is best known for persistent, presumably non-pathogenic, infection and a propensity to co-infect with human immunodeficiency virus or hepatitis C virus. However, unique attributes, such as the increased risk of malignancy or immune modulation, have been recently recognized for HPgV. We have identified a unique case of a woman with high levels HPgV infection in two pregnancies, which occurred 4 years apart and without evidence of human immunodeficiency virus or hepatitis C virus infection. The second pregnancy was complicated by congenital heart disease. A high level of HPgV infection was detected in the maternal blood from different trimesters by RT-PCR and identified as HPgV type 1 genotype 2 in both pregnancies. In the second pregnancy, the decidua and intervillous tissue of the placenta were positive for HPgV by PCR but not the chorion or cord blood (from both pregnancies), suggesting no vertical transmission despite high levels of viremia. The HPgV genome sequence was remarkably conserved over the 4 years. Using VirScan, sera antibodies for HPgV were detected in the first trimester of both pregnancies. We observed the same anti-HPgV antibodies against the non-structural NS5 protein in both pregnancies, suggesting a similar non-E2 protein humoral immune response over time. To the best of our knowledge, this is the first report of persistent HPgV infection involving placental tissues with no clear indication of vertical transmission. Our results reveal a more elaborate viral-host interaction than previously reported, expand our knowledge about tropism, and opens avenues for exploring the replication sites of this virus

The quality of energy- and macronutrient-balanced diets regulates host susceptibility to influenza in mice

Modulation of individual macronutrients or caloric density is known to regulate host resistance to infection in mice. However, the impact of diet composition, independent of macronutrient and energy content, on infection susceptibility is unclear. We show that two laboratory rodent diets, widely used as standard animal feeds and experimental controls, display distinct abilities in supporting mice during influenza infection. Mice placed on the highly processed AIN93G showed increased mortality to infection compared with those on a grain-based chow diet, suggesting a detrimental role for highly processed food in host defense. We further demonstrate that the heightened susceptibility of AIN93G-fed mice was associated with the failure in homeostasis restoration mediated by the cytokine interferon (IFN)-γ. Our findings show that diet composition calibrates host survival threshold by regulating adaptive homeostasis and highlights a pivotal role for extrinsic signals in host phenotype and outcome of host-pathogen interaction

Life-threatening influenza pneumonitis in a child with inherited IRF9 deficiency

Life-threatening pulmonary influenza can be caused by inborn errors of type I and III IFN immunity. We report a 5-yr-old child with severe pulmonary influenza at 2 yr. She is homozygous for a loss-of-function IRF9 allele. Her cells activate gamma-activated factor (GAF) STAT1 homodimers but not IFN-stimulated gene factor 3 (ISGF3) trimers (STAT1/STAT2/IRF9) in response to IFN-α2b. The transcriptome induced by IFN-α2b in the patient's cells is much narrower than that of control cells; however, induction of a subset of IFN-stimulated gene transcripts remains detectable. In vitro, the patient's cells do not control three respiratory viruses, influenza A virus (IAV), parainfluenza virus (PIV), and respiratory syncytial virus (RSV). These phenotypes are rescued by wild-type IRF9, whereas silencing IRF9 expression in control cells increases viral replication. However, the child has controlled various common viruses in vivo, including respiratory viruses other than IAV. Our findings show that human IRF9- and ISGF3-dependent type I and III IFN responsive pathways are essential for controlling IAV

Disrupting Circadian Homeostasis of Sympathetic Signaling Promotes Tumor Development in Mice

and why disruption of circadian rhythm may lead to tumorigenesis. oncogenic potential, leading to tumor development in the same organ systems in wild-type and circadian gene-mutant mice. is a clock-controlled physiological function. The central circadian clock paces extracellular mitogenic signals that drive peripheral clock-controlled expression of key cell cycle and tumor suppressor genes to generate a circadian rhythm in cell proliferation. Frequent disruption of circadian rhythm is an important tumor promoting factor

Signal irreproducibility in high-field solution magnetic resonance experiments caused by spin turbulence

Turbulent spin dynamics arising from the joint action of radiation damping and the distant dipolar field are shown to generate irreproducible measurements in popular high-field, gradient-based magnetic resonance (MR) experiments, undermining the prevailing assumption of essentially predictable observables in MR. Sizeable fluctuations in echo amplitudes are reported and numerically simulated for pulsed gradient spin echo and stimulated echo diffusion measurements. The underlying microscopic dynamical instability is characterized by analysis of the finite-time Lyapunov exponents. Perturbations to the modulated magnetization are shown to render magic-angle gradients ineffective in suppressing signal fluctuations. Alternative approaches are suggested for cancelling out the feedback interactions leading to spin turbulence

Does MR arthrography cause intracranial gadolinium deposition?

Purpose: To determine (i) whether intra-articular gadolinium from MR arthrography (MRA) results in gadolinium deposition in the brain and (ii) whether there is a correlation between intra-articular gadolinium dose and intracranial gadolinium deposition. Materials and methods: This retrospective study was institutional review board (IRB) approved and HIPAA compliant. The study group included consecutive adult patients who had undergone MRA of the hip or shoulder and subsequent MRI of the brain. None of the patients had a history of intravenous gadolinium exposure. A control group of patients of similar age and sex who were never exposed to gadolinium and had brain MRIs available was included. Signal intensities (SI) of four brain regions: pons, dentate nuclei (DN), globus pallidi (GP), and thalamus (Thal) normalized to cerebrospinal fluid (CSF) and expressed in SI ratios were measured on T1-weighted non-contrast MR images. Groups were compared using the student’s t test. Linear correlation analysis of gadolinium dose and brain SI ratios was performed, and Pearson correlation coefficients (r) are reported. Results: We identified 109 patients (mean age 44 ± 14 years, 54% men) who had undergone MRA and 149 controls of similar age and sex distribution. There was no significant difference in mean SI ratios of the brain regions between patients and controls: pons/CSF (p = 0.7), DN/CSF (p = 0.4), GP/CSF (p > 0.99), Thal/CSF (p = 0.3). Within the MRA group, gadolinium dose was not associated with SI ratios (p > 0.2). Conclusion: Our study found no MR evidence of intracranial gadolinium deposition following MRA. In addition, there was no association between intra-articular gadolinium dose and SI ratios in commonly affected regions of the brain

Transcriptome and Literature Mining Highlight the Differential Expression of ERLIN1 in Immune Cells during Sepsis

Sepsis results from the dysregulation of the host immune system. This highly variable disease affects 19 million people globally, and accounts for 5 million deaths annually. In transcriptomic datasets curated from public repositories, we observed a consistent upregulation (3.26–5.29 fold) of ERLIN1—a gene coding for an ER membrane prohibitin and a regulator of inositol 1, 4, 5-trisphosphate receptors and sterol regulatory element-binding proteins—under septic conditions in healthy neutrophils, monocytes, and whole blood. In vitro expression of the ERLIN1 gene and proteins was measured by stimulating the whole blood of healthy volunteers to a combination of lipopolysaccharide and peptidoglycan. Septic stimulation induced a significant increase in ERLIN1 expression; however, ERLIN1 was differentially expressed among the immune blood cell subsets. ERLIN1 was uniquely increased in whole blood neutrophils, and confirmed in the differentiated HL60 cell line. The scarcity of ERLIN1 in sepsis literature indicates a knowledge gap between the functions of ERLIN1, calcium homeostasis, and cholesterol and fatty acid biosynthesis, and sepsis. In combination with experimental data, we bring forth the hypothesis that ERLIN1 is variably modulated among immune cells in response to cellular perturbations, and has implications for ER functions and/or ER membrane protein components during sepsis

Does MR arthrography cause intracranial gadolinium deposition?

PURPOSE: To determine (i) whether intra-articular gadolinium from MR arthrography (MRA) results in gadolinium deposition in the brain and (ii) whether there is a correlation between intra-articular gadolinium dose and intracranial gadolinium deposition. MATERIALS AND METHODS: This retrospective study was institutional review board (IRB) approved and HIPAA compliant. The study group included consecutive adult patients who had undergone MRA of the hip or shoulder and subsequent MRI of the brain. None of the patients had a history of intravenous gadolinium exposure. A control group of patients of similar age and sex who were never exposed to gadolinium and had brain MRIs available was included. Signal intensities (SI) of four brain regions: pons, dentate nuclei (DN), globus pallidi (GP), and thalamus (Thal) normalized to cerebrospinal fluid (CSF) and expressed in SI ratios were measured on T1-weighted non-contrast MR images. Groups were compared using the student's t test. Linear correlation analysis of gadolinium dose and brain SI ratios was performed, and Pearson correlation coefficients (r) are reported. RESULTS: We identified 109 patients (mean age 44 ± 14 years, 54% men) who had undergone MRA and 149 controls of similar age and sex distribution. There was no significant difference in mean SI ratios of the brain regions between patients and controls: pons/CSF (p = 0.7), DN/CSF (p = 0.4), GP/CSF (p > 0.99), Thal/CSF (p = 0.3). Within the MRA group, gadolinium dose was not associated with SI ratios (p > 0.2). CONCLUSION: Our study found no MR evidence of intracranial gadolinium deposition following MRA. In addition, there was no association between intra-articular gadolinium dose and SI ratios in commonly affected regions of the brain

Virome Analysis and Association of Positive Coxsackievirus B Serology during Pregnancy with Congenital Heart Disease

Background: We have previously shown coxsackievirus B (CVB) to be a potent inducer of congenital heart disease (CHD) in mice. The clinical relevance of these findings in humans and the roles of other viruses in the pathogenesis of CHD remain unknown. Methods: We obtained plasma samples, collected at all trimesters, from 89 subjects (104 pregnancies), 73 healthy controls (88 pregnancies), and 16 with CHD–affected birth (16 pregnancies), from the Perinatal Family Tissue Bank (PFTB). We performed CVB IgG/IgM serological assays on plasma. We also used ViroCap sequencing and PCR to test for viral nucleic acid in plasma, circulating leukocytes from the buffy coat, and in the media of a co-culture system. Results: CVB IgG/IgM results indicated that prior exposure was 7.8 times more common in the CHD group (95% CI, 1.14–54.24, adj. p-value = 0.036). However, the CVB viral genome was not detected in plasma, buffy coat, or co-culture supernatant by molecular assays, although other viruses were detected. Conclusion: Detection of viral nucleic acid in plasma was infrequent and specifically no CVB genome was detected. However, serology demonstrated that prior CVB exposure is higher in CHD-affected pregnancies. Further studies are warranted to understand the magnitude of the contribution of the maternal blood virome to the pathogenesis of CHD