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.

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.

Thyroid hormone suppression in feeder pigs following polymicrobial or porcine reproductive and respiratory syndrome virus-2 challenge

2021 ◽  
Author(s):  
J Alex Pasternak ◽  
Daniel J MacPhee ◽  
Joan K Lunney ◽  
Raymond R R Rowland ◽  
PigGen Canada ◽  
...  
Keyword(s):  
Viral Load ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Average Daily Gain ◽  
Respiratory Syndrome Virus ◽  
Post Inoculation ◽  
Serum Samples ◽  
Cross Sectional ◽  
Post Exposure ◽  
Daily Gain

Abstract Thyroid hormones are powerful regulators of growth, development and basal metabolic rate and can be dysregulated under conditions of severe stress or illness. To understand the role of these hormones in porcine disease response, serum samples were obtained from 3 batches of nursery-aged pigs (n=208) exposed to a natural polymicrobial disease challenge with an array of bacterial and viral pathogens. Levels of total thyroxin (T4) and triiodothyronine (T3) assessed in sera by radioimmunoassay (RIA), decreased significantly by 14 days post exposure (DPE). Levels of T3 partially rebounded by 48 DPE, while T4 levels remain depressed. Post-exposure T3 and T4 levels were positively correlated with acute and long-term average daily gain. Cross-sectional sampling of animals maintained at the high health source farms, showed no equivalent change in either hormone when managed under standard industry conditions. To further elucidate the effect of PRRSV-infection on thyroid hormone levels, archived sera over 42 days post inoculation (DPI) from nursery pigs (N=190) challenged with one of two PRRSV2 strains by the PRRS Host Genetics Consortium (PHGC) were similarly assessed, with animals selected in a two-by-two design, to investigate biological extremes in average daily gain (ADG) and viral load. All animals showed a similar decrease in both thyroid hormones reaching a minimum at 7 DPI and returning to near pre challenge levels by 42 DPI. Post challenge T3 and T4 levels were significantly greater in high ADG groups, with no significant association with viral load or strain. The results of this study demonstrate porcine susceptibility to thyroid disruption in response to disease challenge and demonstrate a relationship between this response and growth performance.

scholarly journals Viral load and antibody levels in patients with COVID-19

2021 ◽  
Vol 8 (3) ◽  
pp. 010-018
Author(s):  
Iva Christova ◽  
Iva Trifonova ◽  
Teodora Gladnishka ◽  
Elena Dragusheva ◽  
Georgi Popov ◽  
...  
Keyword(s):  
Viral Load ◽  
High Viral Load ◽  
Igg Antibodies ◽  
Rt Pcr ◽  
Serum Samples ◽  
Weekly Basis ◽  
Specific Antibody Response ◽  
Viral Loads ◽  
Antibody Levels ◽  
Kinetics Of

Relations between viral load, antibody levels and COVID-19 severity are not well studied and results from such investigations are controversial. In this study, we investigated kinetics of viral load and antibody responses to SARS-CoV-2 in 20 patients with COVID-19 and analysed the association with disease severity. The patients were followed on weekly basis within the first month after the onset and then once per month for the next 4 months. Serum samples were tested for IgA, IgM, and IgG antibodies against SARS-CoV-2 using ELISA tests. SARS-CoV-2 viral load in nasopharyngeal swabs was measured by quantitative Realtime RT-PCR. For vast majority of the patients, the viral loads were at their highest levels at presentation and then declined gradually. Despite development of specific antibody response 7-11 days after the onset of COVID-19, SARS-CoV-2 RNA was still detected in nasopharyngeal swabs of most of the patients. There was no direct link between viral load and severity of COVID-19: some of mild and some of severe cases started with a high viral load. There was a relationship between the time from the onset of the disease and the viral load: the highest viral load was in the first days. In more severe cases, there was a tendency for slower reduction in viral load and longer detection of SARS-CoV-2 virus. Levels of the specific antibodies increased earlier and to higher levels and were present for longer time in patients with more severe manifestations of COVID-19 than in those with milder disease.

scholarly journals Clinical, immunological and genomic characterization of asymptomatic and symptomatic cases with SARS-CoV-2 infection, India

2021 ◽  
Author(s):  
Sanchari Chatterjee ◽  
Ankita Datey ◽  
Soumya Sengupta ◽  
Arup Ghosh ◽  
Atimukta Jha ◽  
...  
Keyword(s):  
Viral Load ◽  
Biochemical Parameters ◽  
Mutational Analysis ◽  
Control Strategies ◽  
High Viral Load ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Serum Samples ◽  
Asymptomatic Patients ◽  
Significant Difference

Background: The current global pandemic of Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 led to the investigation with clinical, biochemical, immunological and genomic information of the patients to understand the pathophysiology of this viral infection. Methods: Samples were collected from six asymptomatic and six symptomatic SARS-CoV-2 confirmed hospitalized patients in Bhubaneswar, Odisha, India. Clinical details, biochemical parameters, treatment regime were collected from hospital, viral load was determined by RT-PCR, levels of cytokines and circulating antibodies in plasma were assessed by Bioplex and isotyping respectively. In addition, the whole genome sequencing of viral strains and mutational analysis were carried out. Findings Analysis of the biochemical parameters highlighted the increased levels of C-Reactive protein (CRP), lactate dehydrogenase (LDH), serum SGPT, serum SGOT and ferritin in symptomatic patients indicating that patients with higher levels of few biochemical parameters might experience severe pathophysiological complications after SARS-CoV-2 infection. This was also observed that symptomatic patients were mostly with one or more comorbidities, especially diabetes (66.6%). Surprisingly the virological estimation revealed that there was no significant difference in viral load of oropharyngeal (OP) samples between the two groups. This suggests that the viral load in OP sample does not correlate with disease severity and both asymptomatic and symptomatic patients are equally capable of transmitting the virus. Whereas, viral load was higher in plasma and serum samples of symptomatic patients suggesting that the development of clinical complications is mostly associated to high viral load in plasma and serum. This also demonstrated that the patients with high viral load in plasma and serum samples were found to develop sufficient amounts of antibodies (IgG, IgM and IgA). Interestingly, the levels of 7 cytokines (IL-6, IL-1@, IP-10, IL-8, IL-10, IFN-@2, IL-15) were found to be highly elevated in symptomatic patients, while three cytokines (soluble CD40L, GRO and MDC) were remarkably higher in asymptomatic patients. Therefore, this data suggest that cytokines and chemokines may serve as predictive indicator of SARS-CoV-2 infection and contribute to understand the pathogenesis of COVID-19. The whole genome sequence analysis revealed that the current isolates were clustered with 19B, 20A and 20B clades, however acquired 11 additional changes in Orf1ab, spike, Orf3a, Orf8 and nucleocapsid proteins. The data also confirmed that the D614G mutation in spike protein is mostly linked with severe SARS-CoV-2 infection as two patients with this mutation passes away. Interpretation This is the first comprehensive study of SARS CoV-2 patients from India. This will contribute to a better understanding of the pathophysiology of SARS-CoV-2 infection and advance in the implementation of effective disease control strategies.

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.

Pathological features of the sequence in pregnant women with delayed fetal growth

2019 ◽  
pp. 50-54
Author(s):  
V.O. Golyanovskiy ◽  
◽  
Ye.O. Didyk ◽  
Keyword(s):  
Pregnant Women ◽  
Intrauterine Growth Restriction ◽  
Normal Development ◽  
Intrauterine Infection ◽  
Normal Pregnancy ◽  
Growth Restriction ◽  
Control Group ◽  
Intrauterine Growth ◽  
Increased Risk ◽  
Infection And Inflammation

Pregnant women with intrauterine growth restriction (IUGR) have an increased risk of adverse perinatal and long-term complications compared with the birth of children with normal body weight. Thus, IUGR is one of the main challenges for the global health system, especially in poor and developing countries. Morpho-functional studies of the placentas help in determining the causes of IUGR, and therefore, timely prevent complications in pregnant women with IUGR. The objective: The purpose of this study is to investigate various morphometric and pathomorphological changes in the placenta, including inflammatory, in cases of IUGR, and to establish a correlation of these results with the etiology and complications for the fetus. Materials and methods. In the current study, 54 placentas of the fetuses with IUGR (the main group) were compared with 50 placentas of the fetuses with normal development (control group). The criteria for the inclusion of IUGR were gestational age more than 30 weeks and all fetuses with a weight less than 10th percentile for this period of pregnancy. The placenta material was studied pathomorphologically with laboratory screening for infection and inflammation. Similarly, the results were determined for placentas of the fetuses with normal development compared to placentas with IUGR. Results. The placenta study showed the presence of calcification in the case of IUGR, as well as in the case of prolonged pregnancy. However, calcification of the placenta in the case of IUGR was more progressive compared with placenta in the normal pregnancy. In addition, the presence of intrauterine infection and inflammation was observed, which could also lead to an adverse outcome for the further progression of pregnancy with IUGR. Conclusion. A comparative macro- and microscopic pathomorphological study of the placentas in the two groups has shown a significant increase in the pathological changes in all the anatomical structures of the fetuses with IUGR. Key words: Intrauterine growth restriction (IUGR), fetal weight, pathomorphological changes of the placenta.

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 Treatment of HIV-associated facial lipoatrophy: impact on infection progression assessed by viral load and CD4 count

2013 ◽  
Vol 88 (4) ◽  
pp. 570-577 ◽  
Author(s):  
Flávia Machado Gonçalves Soares ◽  
Izelda Maria Carvalho Costa
Keyword(s):  
Viral Load ◽  
Disease Progression ◽  
Statistical Significance ◽  
Undetectable Viral Load ◽  
Fat Distribution ◽  
Cd4 Count ◽  
Before And After ◽  
Facial Lipoatrophy ◽  
A Prospective Study ◽  
The Impact

BACKGROUND: HIV/AIDS-Associated Lipodystrophy Syndrome includes changes in body fat distribution, with or without metabolic changes. The loss of fat from the face, called facial lipoatrophy, is one of the most stigmatizing signs of the syndrome.OBJECTIVES:To evaluate the effect of FL treatment using polymethylmethacrylate (PMMA) implants on disease progression, assessed by viral load and CD4 cell count.METHODS: This was a prospective study of 44 patients treated from July 2009 to December 2010. Male and female patients, aged over 18 years, with clinically detectable FL and who had never been treated were included in the study. PMMA implantation was done to fill atrophic areas. Laboratory tests were conducted to measure viral load and CD4 count before and after treatment.RESULTS: Of the 44 patients, 72.72% were male and 27.27% female, mean age of 44.38 years. Before treatment, 82% of patients had undetectable viral load, which increased to 88.6% after treatment, but without statistical significance (p = 0.67). CD4 count before treatment ranged from 209 to 1293, averaging 493.97. After treatment, the average increased to 548.61. The increase in CD4 count after treatment was statistically significant with p = 0.02.CONCLUSION: The treatment of FL with PMMA implants showed a statistically significant increase in CD4 count after treatment, revealing the impact of FL treatment on disease progression. Viral load before and after treatment did not vary significantly.

scholarly journals PRRSV detection by qPCR in processing fluids and serum samples collected in a positive stable breeding herd following mass vaccination of sows with a modified live vaccine

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
A. Lebret ◽  
P. Berton ◽  
V. Normand ◽  
I. Messager ◽  
N. Robert ◽  
...  
Keyword(s):  
The United States ◽  
Live Vaccine ◽  
Mass Vaccination ◽  
Respiratory Syndrome Virus ◽  
Serum Samples ◽  
Blood Samples ◽  
Stability Monitoring ◽  
Breeding Herd ◽  
Modified Live Vaccine ◽  
Processing Fluid

AbstractIn the last two decades, in France, Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) stabilization protocols have been implemented using mass vaccination with a modified live vaccine (MLV), herd closure and biosecurity measures. Efficient surveillance for PRRSV is essential for generating evidence of absence of viral replication and transmission in pigs. The use of processing fluid (PF) was first described in 2018 in the United States and was demonstrated to provide a higher herd-level sensitivity compared with blood samples (BS) for PRRSV monitoring. In the meantime, data on vertical transmission of MLV viruses are rare even as it is a major concern. Therefore, veterinarians usually wait for several weeks after a sow mass vaccination before starting a stability monitoring. This clinical study was conducted in a PRRSV-stable commercial 1000-sow breed-to-wean farm. This farm suffered from a PRRS outbreak in January 2018. After implementing a stabilisation protocol, this farm was controlled as stable for more than 9 months before the beginning of the study. PF and BS at weaning were collected in four consecutive batches born after a booster sow mass MLV vaccination. We failed to detect PRRSV by qPCR on PF and BS collected in a positive-stable breeding herd after vaccination with ReproCyc® PRRS EU (Boehringer Ingelheim, Ingelheim, Germany).

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