Nipah virus Bangladesh infection elicits organ-specific innate and inflammatory responses in the marmoset model

2021 ◽  
Author(s):  
Christian S Stevens ◽  
Jake Lowry ◽  
Terry Juelich ◽  
Colm Atkins ◽  
Kendra Johnson ◽  
...  

The common marmoset (Callithrix jacchus) has, in recent years, received more recognition as an ideal non-human primate (NHP) model for studies at high-biocontainment due to its smaller size and relative ease of handling. Here, we evaluated the susceptibility and pathogenesis of Nipah virus Bangladesh strain (NiVB) infection in marmosets. Four marmosets were infected via the intranasal and intratracheal route and monitored for disease development. All four subjects developed fatal disease between days 8 and 11 post infection, with three animals showing severe respiratory disease and one marmoset recapitulating the neurologic clinical symptoms seen in humans, as well as cardiomyopathy on gross pathology. We obtained histopathological data, quantified genome copies on >25 tissue-types, and performed RNA-seq on six different organs from all infected and control marmosets. Three out of four marmosets showed pulmonary edema and hemorrhage as well as multi-focal hemorrhagic lymphadenopathy. In all animals, syncytia were evident in endothelial cells in pulmonary vessels, cells in alveolar septum, and in splenic follicles or red pulp. To define the organ-specific innate and inflammatory responses, we performed RNA-seq on six different organs from all infected and compared to naive non-infected marmoset tissues. RNA-seq gave 17.4 million reads per sample on average, with the most highly infected tissue sample, the lung of one marmoset, containing >180,000 virus-specific reads. NiV V and W transcripts comprised ~40% of all phosphoprotein-derived transcripts with V and W being very close to each other proportionally. Principal component analysis showed that in brain stem, the marmoset exhibiting neurological symptoms displayed a unique RNA transcriptome relative even to other infected marmosets. Upregulated genes in the various tissues belonged to distinct GO pathways. Additionally, one male and female animal had detectable viral reads in their ovaries (27,120) and testes (858). Our results provide a more comprehensive understanding of NiV pathogenesis in an accessible and novel NHP model, closely reflecting clinical disease as observed in NiV patients.

2019 ◽  
Vol 26 (11) ◽  
pp. 1485-1492
Author(s):  
Xiaochun Yi ◽  
Jie Zhang ◽  
Huixiang Liu ◽  
Tianxia Yi ◽  
Yuhua Ou ◽  
...  

The adverse clinical result and poor treatment outcome in recurrent spontaneous abortion (RSA) make it necessary to understand the pathogenic mechanism. The mating combination CBA/J × DBA/2 has been widely used as an abortion-prone model compared to DBA/2-mated CBA/J mice. Here, we used RNA-seq to get a comprehensive catalogue of genes differentially expressed between survival placenta in abortion-prone model and control. Five hundred twenty-four differentially expressed genes were obtained followed by clustering analysis, Gene Ontology analysis, and pathway analysis. We paid more attention to immune-related genes namely “immune response” and “immune system process” including 33 downregulated genes and 28 upregulated genes. Twenty-one genes contribute to suppressing immune system and 7 are against it. Six genes were validated by reverse transcription-polymerase chain reaction, namely Ccr1l1, Tlr4, Tgf-β1, Tyro3, Gzmb, and Il-1β. Furthermore, Tlr4, Tgf-β1, and Il-1β were analyzed by Western blot. Such immune profile gives us a better understanding of the complicated immune processing in RSA and immunosuppression can rescue pregnancy loss.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10668
Author(s):  
Juan Wang ◽  
Xiongfei Wu ◽  
Yafang Tu ◽  
Jianzhong Dang ◽  
Zhitao Cai ◽  
...  

Long noncoding RNAs (lncRNAs) are persistently expressed and have been described as potential biomarkers and therapeutic targets in various diseases. However, there is limited information regarding lncRNA expression in the tissue of kidney exhibiting lupus nephritis (LN)a serious complication of systemic lupus erythematosus (SLE). In this study, RNA sequencing (RNA-seq) was performed to characterize the lncRNA and mRNA expression in kidney tissues from LN (MRL/lpr) and control mice. We identified 12,979 novel lncRNAs in mouse. The expression profiles of both mRNAs and lncRNAs were differed significantly between LN and control mice. In particular, there were more upregulated lncRNAs and mRNAs than downregulated ones in the kidney tissues of LN mice. However, GO analysis showed that more downregulated genes were enriched in immune and inflammatory response-associated pathways. KEGG analysis showed that both downregulated and upregulated genes were enriched in a number of pathways, including the SLE pathway, and approximately half of these SLE-associated genes encoded inflammatory factors. Moreover, we observed that 2,181 DElncRNAs may have targeted and regulated the expression of 778 mRNAs in LN kidney tissues. The results of this study showed that 11 DElncRNAs targeted and were co-expressed with six immune and SLE-associated genes. qPCR analysis confirmed that lncRNA Gm20513 positively regulated the expression of the SLE-associated gene H2-Aa. In conclusion, the results of our study demonstrates that lncRNAs influence the progression of LN and provide some cues for further study of lncRNAs in LN. These results regarding the lncRNA-mRNAregulatory network may have important value in LN diagnosis and therapy.


2019 ◽  
Author(s):  
Akanksha Rajput ◽  
Manoj Kumar

AbstractThe Nipah virus is responsible various outbreaks among countries of south east Asia, most recent is in Kerala, India. It is considered to be highly contagious and having a range of vectors for transmission. The condition worsens due to the lack of effective inhibitors. This study is first study, which focused to detect the differentially expressed genes among two different NiV studies from 2012 and 2017. The transcriptomic profiling data were retrieved from the sequence archives. The multivariate gene enrichment analyses were performed on the log transformed data from them using pathway, gene ontology, disease, reactome, etc. The comparison study suggests that the down regulated differentially expressed genes are common among them as compared to up regulated ones with statistical significance. However, among the diseased category the upregulated genes are mostly from metabolic pathways and diseased category like metabolic pathways, heart failure, cholesterol metabolism while the downregulated genes linked to various cancers, and viral diseases like hepatitis, dengue, influenza, etc. We found various small molecules mapped in the pathways which are differentially expressed among the studies, which could be targeted so as to control the Nipah infection. In order to design the inhibitors, our study would be useful to extract the effective and broad-spectrum drug targets.


2020 ◽  
Vol 16 ◽  
Author(s):  
Yasemin Taşcı ◽  
Rahime Bedir Fındık ◽  
Meryem Kuru Pekcan ◽  
Ozan Kaplan ◽  
Mustafa Çelebier

Background: Metabolomics is one of the main areas to understand cellular process at molecular level by analyzing metabolites. In recent years metabolomics has been emerged as key tool to understand molecular basis of disease, find diagnostic and prognostic biomarkers, and develop new treatment opportunities and drug molecules. Objective: In this study, an untargeted metabolite and lipid analysis were performed to identify potential biomarkers on premature ovarian insufficiency plasma samples. 43 POI subject plasma samples were compared with 32 healthy subject plasma samples. Methods: Plasma samples were pooled and extracted using chloroform:methanol:water (3:3:1 v/v/v) mixture. Agilent 6530 LC/MS Q-TOF instrument equipped with ESI source was used for analysis. A C18 column (Agilent Zorbax 1.8 μM, 50 x 2.1 mm) was used for separation of metabolites and lipids. XCMS, an “R software” based freeware program, was used for peak picking, grouping and comparing the findings. Isotopologue Parameter Optimization (IPO) software was used in order to optimize XCMS parameters. The analytical methodology and data mining process were validated according to the literature. Results: 83 metabolite peaks and 213 lipid peaks were found to be in semi-quantitatively and statistically different (fold change >1.5, p <0.05) between the POI plasma samples and control subjects. Conclusion: According to the results, two groups were successfully separated through principal component analysis. Among the peaks, phenyl alanine, decanoyl-L-carnitine, 1-palmitoyllysophosphatidylcholine and PC(O-16:0/2:0) were identified through auto MS/MS and matched with human metabolome database and proposed as plasma biomarker for POI and monitoring the patients in treatment period.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Pengxiu Cao ◽  
Natalie M. Walker ◽  
Russell R. Braeuer ◽  
Serina Mazzoni-Putman ◽  
Yoshiro Aoki ◽  
...  

AbstractForkhead box F1 (FOXF1) is a lung embryonic mesenchyme-associated transcription factor that demonstrates persistent expression into adulthood in mesenchymal stromal cells. However, its biologic function in human adult lung-resident mesenchymal stromal cells (LR-MSCs) remain to be elucidated. Here, we demonstrate that FOXF1 expression acts as a restraint on the migratory function of LR-MSCs via its role as a novel transcriptional repressor of autocrine motility-stimulating factor Autotaxin (ATX). Fibrotic human LR-MSCs demonstrated lower expression of FOXF1 mRNA and protein, compared to non-fibrotic controls. RNAi-mediated FOXF1 silencing in LR-MSCs was associated with upregulation of key genes regulating proliferation, migration, and inflammatory responses and significantly higher migration were confirmed in FOXF1-silenced LR-MSCs by Boyden chamber. ATX is a secreted lysophospholipase D largely responsible for extracellular lysophosphatidic acid (LPA) production, and was among the top ten upregulated genes upon Affymetrix analysis. FOXF1-silenced LR-MSCs demonstrated increased ATX activity, while mFoxf1 overexpression diminished ATX expression and activity. The FOXF1 silencing-induced increase in LR-MSC migration was abrogated by genetic and pharmacologic targeting of ATX and LPA1 receptor. Chromatin immunoprecipitation analyses identified three putative FOXF1 binding sites in the 1.5 kb ATX promoter which demonstrated transcriptional repression of ATX expression. Together these findings identify FOXF1 as a novel transcriptional repressor of ATX and demonstrate that loss of FOXF1 promotes LR-MSC migration via the ATX/LPA/LPA1 signaling axis.


Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 933
Author(s):  
Amin S. Asfor ◽  
Salik Nazki ◽  
Vishwanatha R.A.P. Reddy ◽  
Elle Campbell ◽  
Katherine L. Dulwich ◽  
...  

In order to better understand differences in the outcome of infectious bursal disease virus (IBDV) infection, we inoculated a very virulent (vv) strain into White Leghorn chickens of inbred line W that was previously reported to experience over 24% flock mortality, and three inbred lines (15I, C.B4 and 0) that were previously reported to display no mortality. Within each experimental group, some individuals experienced more severe disease than others but line 15I birds experienced milder disease based on average clinical scores, percentage of birds with gross pathology, average bursal lesion scores and average peak bursal virus titre. RNA-Seq analysis revealed that more severe disease in line W was associated with significant up-regulation of pathways involved in inflammation, cytoskeletal regulation by Rho GTPases, nicotinic acetylcholine receptor signaling, and Wnt signaling in the bursa compared to line 15I. Primary bursal cell populations isolated from uninfected line W birds contained a significantly greater percentage of KUL01+ macrophages than cells isolated from line 15I birds (p < 0.01) and, when stimulated ex vivo with LPS, showed more rapid up-regulation of pro-inflammatory gene expression than those from line 15I birds. We hypothesize that a more rapid induction of pro-inflammatory cytokine responses in bursal cells following IBDV infection leads to more severe disease in line W birds than in line 15I.


Algorithms ◽  
2021 ◽  
Vol 14 (6) ◽  
pp. 174
Author(s):  
Wenxiao Zhao

The stochastic approximation algorithm (SAA), starting from the pioneer work by Robbins and Monro in 1950s, has been successfully applied in systems and control, statistics, machine learning, and so forth. In this paper, we will review the development of SAA in China, to be specific, the stochastic approximation algorithm with expanding truncations (SAAWET) developed by Han-Fu Chen and his colleagues during the past 35 years. We first review the historical development for the centralized algorithm including the probabilistic method (PM) and the ordinary differential equation (ODE) method for SAA and the trajectory-subsequence method for SAAWET. Then, we will give an application example of SAAWET to the recursive principal component analysis. We will also introduce the recent progress on SAAWET in a networked and distributed setting, named the distributed SAAWET (DSAAWET).


2012 ◽  
Vol 4 (1) ◽  
pp. e2012018 ◽  
Author(s):  
Cengiz Bayram ◽  
Ali Fettah ◽  
Nese Yarali ◽  
Abdurrahman Kara ◽  
Fatih Mehmet Azik ◽  
...  

Hepatosplenic candidiasis (HSC) is a form of invasive fungal infection that occurs most commonly in patients with acute leukemia treated with chemotherapy and requires protracted antifungal therapy. Immune reconstitution inflammatory syndrome (IRIS) is best characterized as a dysregulated inflammatory responses triggered by rapid resolution of immunosuppression.We present a child diagnosed with standard-risk precursor B cell-acute lymphoblastic leukemia who developed HSC and Candida-related IRIS during recovery of neutropenia associated with induction chemotherapy. Addition of corticosteroid therapy to antifungal treatment is associated with the resolution of the clinical symptoms and laboratory findings


2021 ◽  
Vol 11 (4) ◽  
pp. 435
Author(s):  
Andreas-Christian Hade ◽  
Mari-Anne Philips ◽  
Ene Reimann ◽  
Toomas Jagomäe ◽  
Kattri-Liis Eskla ◽  
...  

The Mediodorsal (MD) thalamus that represents a fundamental subcortical relay has been underrepresented in the studies focusing on the molecular changes in the brains of subjects with alcohol use disorder (AUD). In the current study, MD thalamic regions from AUD subjects and controls were analyzed with Affymetrix Clariom S human microarray. Long-term alcohol use induced a significant (FDR ≤ 0.05) upregulation of 2802 transcripts and downregulation of 1893 genes in the MD thalamus of AUD subjects. A significant upregulation of GRIN1 (glutamate receptor NMDA type 1) and FTO (alpha-ketoglutarate dependent dioxygenase) was confirmed in western blot analysis. Immunohistochemical staining revealed similar heterogenous distribution of GRIN1 in the thalamic nuclei of both AUD and control subjects. The most prevalent functional categories of upregulated genes were related to glutamatergic and GABAergic neurotransmission, cellular metabolism, and neurodevelopment. The prevalent gene cluster among down-regulated genes was immune system mediators. Forty-two differentially expressed genes, including FTO, ADH1B, DRD2, CADM2, TCF4, GCKR, DPP6, MAPT and CHRH1, have been shown to have strong associations (FDR p < 10−8) with AUD or/and alcohol use phenotypes in recent GWA studies. Despite a small number of subjects, we were able to detect robust molecular changes in the mediodorsal thalamus caused by alcohol emphasizing the importance of deeper brain structures such as diencephalon, in the development of AUD-related dysregulation of neurocircuitry.


2010 ◽  
Vol 78 (11) ◽  
pp. 4763-4772 ◽  
Author(s):  
Raquel M. Gonçalves ◽  
Karina C. Salmazi ◽  
Bianca A. N. Santos ◽  
Melissa S. Bastos ◽  
Sandra C. Rocha ◽  
...  

ABSTRACT Clearing blood-stage malaria parasites without inducing major host pathology requires a finely tuned balance between pro- and anti-inflammatory responses. The interplay between regulatory T (Treg) cells and dendritic cells (DCs) is one of the key determinants of this balance. Although experimental models have revealed various patterns of Treg cell expansion, DC maturation, and cytokine production according to the infecting malaria parasite species, no studies have compared all of these parameters in human infections with Plasmodium falciparum and P. vivax in the same setting of endemicity. Here we show that during uncomplicated acute malaria, both species induced a significant expansion of CD4+ CD25+ Foxp3+ Treg cells expressing the key immunomodulatory molecule CTLA-4 and a significant increase in the proportion of DCs that were plasmacytoid (CD123+), with a decrease in the myeloid/plasmacytoid DC ratio. These changes were proportional to parasite loads but correlated neither with the intensity of clinical symptoms nor with circulating cytokine levels. One-third of P. vivax-infected patients, but no P. falciparum-infected subjects, showed impaired maturation of circulating DCs, with low surface expression of CD86. Although vivax malaria patients overall had a less inflammatory cytokine response, with a higher interleukin-10 (IL-10)/tumor necrosis factor alpha (TNF-α) ratio, this finding did not translate to milder clinical manifestations than those of falciparum malaria patients. We discuss the potential implications of these findings for species-specific pathogenesis and long-lasting protective immunity to malaria.


Sign in / Sign up

Export Citation Format

Share Document