scholarly journals Fetal hypoxia and apoptosis following maternal porcine reproductive and respiratory syndrome virus (PRRSV) infection

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Carolina M. Malgarin ◽  
Fiona Moser ◽  
J. Alex Pasternak ◽  
Glenn Hamonic ◽  
Susan E. Detmer ◽  
...  
Keyword(s):  
Viral Load ◽  
Strong Evidence ◽  
Fetal Death ◽  
Fetal Heart ◽  
High Viral Load ◽  
Group Differences ◽  
Respiratory Syndrome Virus ◽  
Third Trimester ◽  
Fetal Tissues ◽  
The Brain

Abstract Background Mechanisms of fetal death following maternal PRRSV2 infection remain uncharacterized, although hypoxia from umbilical cord lesions and/or placental detachment due to apoptosis are hypothesized. We performed two experiments examining hypoxia and apoptosis in PRRSV-infected and non-infected, third-trimester fetuses to elucidate possible associations with fetal death. Fetuses were selected based on four phenotypic infection groups: fetuses from non-challenged control gilts (CTRL); low viral load fetuses (LVL; Exp 1) or uninfected fetuses (UNINF; Exp 2) from inoculated gilts; viable high viral load fetuses (HVL-VIA); and HVL meconium-stained fetuses (HVL-MEC). Results In experiment 1, paraffin embedded fetal tissues collected 21 days post maternal infection (DPI) were examined for DNA fragmentation associated with apoptosis. Positively stained foci were larger and more numerous (P < 0.05) in heart, liver, and thymus of HVL-VIA and HVL-MEC compared to CTRL and LVL fetuses. In experiment 2, group differences in gene expression within the hypoxia (HIF1a, IDO1, VEGFa, LDHA, NOS2, NOX1) and apoptosis (CASP3, CASP7, CASP8, CASP9, RIPK1, RIPK3) pathways were assessed by RT-qPCR in fetal tissues collected at 12 DPI. High viral load fetuses showed differential expression relative to the CTRL and UNINF (P < 0.05 for all). Brain tissue from HVL-VIA and HVL-MEC fetuses presented increased expression of CASP7, CASP8, RIPK3, HIF1a and IDO1. Fetal heart showed increased expression of CASP8, HIF1a, IDO and NOX1 and a decrease in NOS2 expression in infected groups. CASP7, CASP9, RIPK1 and RIPK3 were only increased in the heart of HVL-VIA while VEGFa was only increased for HVL-MEC fetuses. Thymus from HVL-MEC had decreased expression of CASP9 and there was increased IDO1 in all infected fetuses. Conclusions There is strong evidence of apoptosis occurring in the heart, liver and thymus of highly viral load fetuses at 21 DPI. Furthermore, there was clear upregulation of apoptotic genes in the heart of high viral load infected fetuses and less prominent upregulation in the brain of PRRSV-infected fetuses, whereas thymus appears to be spared at 12 DPI. There was no strong evidence of hypoxia at 12 DPI in brain and thymus but some indication of hypoxia occurring in fetal heart.

scholarly journals Fetal Metabolomic Alterations Following Porcine Reproductive and Respiratory Syndrome Virus Infection

2020 ◽  
Vol 7 ◽  
Author(s):  
Carolina M. Malgarin ◽  
Daniel J. MacPhee ◽  
John C. S. Harding
Keyword(s):  
Viral Load ◽  
Disease Progression ◽  
Fetal Death ◽  
Normal Development ◽  
High Viral Load ◽  
Respiratory Syndrome Virus ◽  
Serum Samples ◽  
Intrauterine Growth ◽  
Nmr Techniques ◽  
Near Term

PRRSV infection in third-trimester pregnant sows can lead to fetal death and abortions, although the mechanisms triggering these effects are not well understood. Since resistant and susceptible fetuses can coexist in the same litter, we propose that there may be differential mechanisms used by some fetuses to evade infection and/or disease progression. Our objectives were to investigate possible differences in the metabolome of PRRSV-infected and non-infected fetuses, as well as the interaction of altered intrauterine growth development and PRRSV infection to elucidate possible causes of fetal death following PRRSV infection. Near-term serum samples collected from fetuses on gestation day 106, 21 days post PRRSV-2 infection, were processed by direct flow injection mass spectrometry (DI-MS) and nuclear magnetic resonance (NMR) techniques. Experiment one investigated disease progression with 24 fetuses selected from each of four phenotypic groups: fetuses from non-inoculated gilts (CTRL); fetuses from inoculated gilts that escaped infection (UNINF); infected high viral load viable fetuses (INF); and infected high viral load meconium-stained fetuses (MEC). Experiment two investigated the interaction of intrauterine growth retardation (IUGR) and PRRSV infection by analyzing differences among: non-infected normal development (CON-N); CON-IUGR; PRRS infected normal development (PRRS-N); and PRRS-IUGR. Univariate and multivariate (PCA, PLS-DA) statistics determined group differences among various contrasts, and the most important metabolites associated with disease progression and fetal development. Significant differences in the metabolome were observed, especially between PRRSV-negative fetuses (CTRL and UNINF) and MEC fetuses, while INF fetuses appear to span both groups. The two metabolites with highest variable importance in projection (VIP) scores related to disease progression were alpha-aminoadipic acid (alpha-AAA) and kynurenine (KYN), having the highest concentration in MEC and INF fetuses, respectively, compared to CTRL and UNINF. In experiment two, non-IUGR fetuses were found to have increased levels of lysoPCs, PCs and amino acids compared to IUGR fetuses, while the near complete absence of lysoPCs and PCs in IUGR fetuses, even during infection, indicate a distinctive response to infection compared to non-growth retarded fetuses. Possible markers of PRRSV fetal susceptibility, such as alpha-AAA, kynurenine and lysoPCs, are presented and discussed.

Hyperglycemia and hyperinsulinemia increase glucose utilization in fetal rat tissues

1987 ◽  
Vol 253 (6) ◽  
pp. E616-E620
Author(s):  
A. Leturque ◽  
J. P. Revelli ◽  
S. Hauguel ◽  
J. Kande ◽  
J. Girard
Keyword(s):  
Glucose Utilization ◽  
Fetal Heart ◽  
Blood Glucose Concentration ◽  
Insulin Level ◽  
Rat Tissues ◽  
Exogenous Insulin ◽  
Fetal Tissues ◽  
Hindlimb Muscles ◽  
Metabolic Index ◽  
The Brain

In vivo measurement of glucose utilization by individual tissues of 19-day rat fetuses have been performed using radioactive 2-deoxy-D-glucose technique. In the basal state, glucose metabolic index was 13.6 +/- 0.5 ng.min-1.mg-1 for the whole fetus, 21 +/- 1 in the hindlimb muscles, 13 +/- 2 in the liver, and 16 +/- 2 in the brain, whereas the fetal heart had the highest value: 62 +/- 5 ng.min-1.mg-1. To raise the fetal glycemia, the basal maternal blood glucose concentration of 0.78 +/- 0.02 g/l was elevated to 1.04 +/- 0.02 g/l by mean of hyperglycemic clamps. The fetal hyperglycemia increased glucose metabolic index by 30-100% over basal values in all the tissues tested except in the brain. To raise fetal insulinemia, maternal euglycemic clamp with supraphysiological insulin concentrations were performed, then a fraction (1%) of exogenous insulin crossed the placenta. Fetal plasma insulin concentrations were thus elevated to 180 +/- 32 and 255 +/- 23 microU/ml. The fetal heart increased significantly its glucose metabolic index in response to the lower insulin level. Glucose metabolic index in hindlimb muscles and liver was increased by 50-100% for the highest insulin level, whereas the brain was unaffected by exogenous insulin. We conclude that glucose metabolic index is stimulated by physiological hyperglycemia in individual fetal tissues and that fetal tissues (heart, liver, and muscle) are sensitive to exogenous insulin.

scholarly journals Maternal and fetal predictors of fetal viral load and death in third trimester, type 2 porcine reproductive and respiratory syndrome virus infected pregnant gilts

2015 ◽  
Vol 46 (1) ◽  
Author(s):  
Andrea Ladinig ◽  
Carolyn Ashley ◽  
Susan E Detmer ◽  
Jamie M Wilkinson ◽  
Joan K Lunney ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Syndrome Virus ◽  
Third Trimester

scholarly journals T cells in the brain enhance neonatal mortality during peripheral LCMV infection

2021 ◽  
Vol 17 (1) ◽  
pp. e1009066
Author(s):  
Laurie L. Kenney ◽  
Erik P. Carter ◽  
Anna Gil ◽  
Liisa K. Selin
Keyword(s):  
T Cells ◽  
Viral Load ◽  
T Cell ◽  
Viral Infections ◽  
Cd8 T Cell ◽  
High Viral Load ◽  
Viral Control ◽  
Neonatal Mice ◽  
The Impact ◽  
The Brain

In adult mice the severity of disease from viral infections is determined by the balance between the efficiency of the immune response and the magnitude of viral load. Here, the impact of this dynamic is examined in neonates. Newborns are highly susceptible to infections due to poor innate responses, lower numbers of T cells and Th2-prone immune responses. Eighty-percent of 7-day old mice, immunologically equivalent to human neonates, succumbed to extremely low doses (5 PFU) of the essentially non-lethal lymphocytic choriomeningitis virus (LCMV-Armstrong) given intraperitoneally. This increased lethality was determined to be dependent upon poor early viral control, as well as, T cells and perforin as assessed in knockout mice. By day 3, these neonatal mice had 400-fold higher viral loads as compared to adults receiving a 10,000-fold (5X104 PFU) higher dose of LCMV. The high viral load in combination with the subsequent immunological defect of partial CD8 T cell clonal exhaustion in the periphery led to viral entry and replication in the brain. Within the brain, CD8 T cells were protected from exhaustion, and thus were able to mediate lethal immunopathology. To further delineate the role of early viral control, neonatal mice were infected with Pichinde virus, a less virulent arenavirus, or LCMV was given to pups of LCMV-immune mothers. In both cases, peak viral load was at least 29-fold lower, leading to functional CD8 T cell responses and 100% survival.

scholarly journals High viral SARS-CoV-2 load in placenta of patients with hypertensive disorders after COVID-19 during pregnancy

2021 ◽  
Author(s):  
M Fabre ◽  
P Calvo ◽  
S Ruiz-Martinez ◽  
M Peran ◽  
D Oros ◽  
...  
Keyword(s):  
Viral Load ◽  
Group Versus ◽  
High Viral Load ◽  
Control Group ◽  
Rt Pcr ◽  
Third Trimester ◽  
Hypertensive Disorders ◽  
The Moment ◽  
The Relationship ◽  
Control Study

AbstractIntroductionStudies described an increased frequency of hypertensive disorders of pregnancy after a COVID-19 episode. There is limited evidence about SARS-CoV-2 viral load in placenta. This study aimed to investigate the relationship between SARS-CoV-2 viral load in placenta and clinical development of HDP after COVID-19 throughout different periods of gestation.MethodsThis was a case-control study in women with and without gestational hypertensive disorders (HDP) after SARS-CoV-2 infection diagnosed by RT-PCR during pregnancy. Patients were matched by gestational age at the moment of COVID-19 diagnosis. We performed an analysis of SARS-CoV-2 RNA levels in placenta.ResultsA total of 28 women were enrolled. Sixteen patients were diagnosed with COVID-19 during the third trimester and the remaining twelve patients in the others trimesters. Ten placentas (35.7%) were positive for SARS-CoV-2, nine of them (90%) belonged to the HDP group versus one (10%) in control group (p=0.009). Those cases with the highest loads of viral RNA developed severe-preeclampsia.ConclusionThe presence of SARS-CoV-2 was more frequent in placentas of patients with HDP after COVID-19. There seems to be a relationship between high viral load in the placenta and the development of hypertensive disorders. We found SARS-CoV-2 viral load in placenta after birth in mothers infected at the first half of pregnancy, but with negative nasopharyngeal RT-PCR at delivery. Our data suggest that SARS-CoV-2 infection during pregnancy could trigger gestational hypertensive disorders through placenta-related mechanisms.

scholarly journals Up-Regulation of Immune Checkpoints in the Thymus of PRRSV-1-Infected Piglets in a Virulence-Dependent Fashion

2021 ◽  
Vol 12 ◽  
Author(s):  
Inés Ruedas-Torres ◽  
Irene M. Rodríguez-Gómez ◽  
José María Sánchez-Carvajal ◽  
Silvia Guil-Luna ◽  
Fernanda Larenas-Muñoz ◽  
...  
Keyword(s):  
Immune Response ◽  
Viral Load ◽  
T Cell ◽  
High Viral Load ◽  
Lymphoid Organ ◽  
Immune Checkpoints ◽  
Respiratory Syndrome Virus ◽  
Cell Functions ◽  
Virulent Strains ◽  
Thymus Atrophy

Virulent porcine reproductive and respiratory syndrome virus (PRRSV) strains, such as the Lena strain, have demonstrated a higher thymus tropism than low virulent strains. Virulent PRRSV strains lead to severe thymus atrophy, which could be related to marked immune dysregulation. Impairment of T-cell functions through immune checkpoints has been postulated as a strategy executed by PRRSV to subvert the immune response, however, its role in the thymus, a primary lymphoid organ, has not been studied yet. Therefore, the goal of this study was to evaluate the expression of selected immune checkpoints (PD1/PDL1, CTLA4, TIM3, LAG3, CD200R1 and IDO1) in the thymus of piglets infected with two different PRRSV-1 strains. Thymus samples from piglets infected with the low virulent 3249 strain, the virulent Lena strain and mock-infected were collected at 1, 3, 6, 8 and 13 days post-infection (dpi) to analyze PRRSV viral load, relative quantification and immunohistochemical staining of immune checkpoints. PD1/PDL1, CTLA4, TIM3, LAG3 and IDO1 immune checkpoints were significantly up-regulated in the thymus of PRRSV infected piglets, especially in those infected with the virulent Lena strain from 6 dpi onwards. This up-regulation was associated with disease progression, high viral load and cell death. Co-expression of these molecules can affect T-cell development, maturation and selection, negatively regulating the host immune response against PRRSV.

Update in management of hepatitis B in pregnancy and prevention of mother to child hepatitis B transmission

2018 ◽  
Vol 1 (3) ◽  
pp. 1-8
Author(s):  
Naichaya Chamroonkul
Keyword(s):  
Chronic Hepatitis ◽  
Viral Load ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
High Viral Load ◽  
World Population ◽  
Hepatitis B Infection ◽  
Mother To Child Transmission ◽  
Child Transmission ◽  
Mother To Child

Even with two decades of widespread using hepatitis B vaccination, chronic hepatitis B remains a major global health problem. In Thailand, the prevalence of chronic hepatitis B infection was down from 8 - 10% in last decade to 5% recently. Failure to control mother to child transmission is one of the important barriers to the total elimination of hepatitis B infection from world population. In the majority, vertical transmission can be prevented with a universal screening program, immunoprophylaxis by administration of hepatitis B vaccine and hepatitis B immunoglobulin (HBIg) for babies born to mothers with HBV. However, in mothers with a high viral load, the chance of immunoprophylaxis failure remains high. To date, there are standard recommendations by all international liver societies including AASLD, EASL and APASL suggest introducing an antiviral agent during the third trimester to CHB pregnant women with a high viral load. Previous US FDA pregnancy category B agents such as Tenofovir and Telbivudine are allowed through all trimesters of pregnancy and are effective for prevention of mother to child transmission. Breastfeeding for patients who receive antiviral agents can be allowed after a risk-benefit discussion with the patient and family.

scholarly journals Adapting the role of handheld echocardiography during the COVID-19 pandemic: A practical guide

Perfusion ◽  
2021 ◽  
pp. 026765912098653
Author(s):  
Hafiz Naderi ◽  
Shaun Robinson ◽  
Martin J Swaans ◽  
Nina Bual ◽  
Wing-See Cheung ◽  
...  
Keyword(s):  
Viral Load ◽  
Potential Role ◽  
Assessment Tool ◽  
High Viral Load ◽  
First Line ◽  
Scanning Time ◽  
Contagious Disease ◽  
Core Dataset ◽  
Clinical Questions

The COVID-19 pandemic has altered our approach to inpatient echocardiography delivery. There is now a greater focus to address key clinical questions likely to make an immediate impact in management, particularly during the period of widespread infection. Handheld echocardiography (HHE) can be used as a first-line assessment tool, limiting scanning time and exposure to high viral load. This article describes a potential role for HHE during a pandemic. We propose a protocol with a reporting template for a focused core dataset necessary in delivering an acute echocardiography service in the setting of a highly contagious disease, minimising risk to the operator. We cover the scenarios typically encountered in the acute cardiology setting and how an expert trained echocardiography team can identify such pathologies using a limited imaging format and include cardiac presentations encountered in those patients acutely unwell with COVID-19.

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