scholarly journals Rhesus negative males have an enhanced IFNγ-mediated immune response to influenza A virus

2021 ◽  
Author(s):  
Jamie A Sugrue ◽  
Megan Smith ◽  
Celine Posseme ◽  
Bruno Charbit ◽  
Nollaig M Bourke ◽  
...  
Keyword(s):  
Immune Response ◽  
Influenza A Virus ◽  
Influenza A ◽  
Viral Infections ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Human Immunology ◽  
Specific Effects ◽  
Specific Analysis ◽  
D Antigen

The Rhesus D antigen (RhD) has been associated with susceptibility to several viral infections. Reports suggest that RhD-negative individuals are better protected against infectious diseases and have overall better health. However, potential mechanisms contributing to these associations have not yet been defined. Here, we used transcriptomic and genomic data from the Milieu Interieur cohort of 1000 healthy individuals to explore the effect of RhD on immune responses. We used the rs590787 SNP in the RHD gene to classify the 1000 donors as either RhD-positive or -negative. Whole blood was stimulated with LPS, polyIC, and the live influenza A virus and the NanoString human immunology panel of 560 genes used to assess donor immune response and to investigate sex specific effects. Using regression analysis, we observed no significant differences in responses to polyIC or LPS between RhD-positive and -negative individuals. However, upon sex-specific analysis, we observed over 30 differentially expressed genes (DEGs) between RhD-positive (n=401) and RhD-negative males (n=78). Interestingly these Rhesus-associated differences were not seen in females. Further investigation, using gene set enrichment analysis, revealed enhanced IFNγ signalling in RhD-negative males. This amplified IFNγ signalling axis may explain the increased viral resistance previously described in RhD-negative individuals.

scholarly journals RNA-seq Analysis of Influenza A Virus-Induced Transcriptional Changes in Mice Lung and Its Possible Implications for the Virus Pathogenicity in Mice

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2031
Author(s):  
Tianxin Ma ◽  
Abdou Nagy ◽  
Guanlong Xu ◽  
Lingxiang Xin ◽  
Danqi Bao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Influenza A Virus ◽  
Influenza A ◽  
Enrichment Analysis ◽  
Alveolar Epithelial Cells ◽  
Gene Set Enrichment Analysis ◽  
Target Cells ◽  
Alveolar Epithelial ◽  
Raw264.7 Macrophages ◽  
Immune Related Genes

The influenza A virus (IAV) is an important cause of respiratory disease worldwide. It is well known that alveolar epithelial cells are the target cells for the IAV, but there is relatively limited knowledge regarding the role of macrophages during IAV infection. Here, we aimed to analyze transcriptome differences in mouse lungs and macrophage (RAW264.7) cell lines infected with either A/California/04/2009 H1N1 (CA09) or A/chicken/SD/56/2015 H9N2 (SD56) using deep sequencing. The uniquely differentially expressed genes (UDEGs) were analyzed with the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases; the results showed that the lungs infected with the two different viruses had different enrichments of pathways and terms. Interestingly, CA09 virus infection in mice was mostly involved with genes related to the extracellular matrix (ECM), while the most significant differences after SD56 infection in mice were in immune-related genes. Gene set enrichment analysis (GSEA) of RAW264.7 cells revealed that regulation of the cell cycle was of great significance after CA09 infection, whereas the regulation of the immune response was most enriched after SD56 infection, which was consistent with analysis results in the lung. Similar results were obtained from weighted gene co-expression network analysis (WGCNA)，where cell cycle regulation was extensively activated in RAW264.7 macrophages infected with the CA09 virus. Disorder of the cell cycle is likely to affect their normal immune regulation, which may be an important factor leading to their different prognoses. These results provide insight into the mechanism of the CA09 virus that caused a pandemic and explain the different reactivities of monocytes/macrophages infected by H9N2 and H1N1 IAV subtypes.

scholarly journals Links between fecal microbiota and the response to vaccination against influenza A virus in pigs

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Marion Borey ◽  
Fany Blanc ◽  
Gaëtan Lemonnier ◽  
Jean-Jacques Leplat ◽  
Deborah Jardet ◽  
...  
Keyword(s):  
Immune Response ◽  
Influenza A Virus ◽  
Influenza A ◽  
16S Rrna Gene Sequencing ◽  
Serum Levels ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Vaccine Response ◽  
Specific Igg ◽  
Rrna Gene Sequencing

AbstractThis study describes the associations between fecal microbiota and vaccine response variability in pigs, using 98 piglets vaccinated against the influenza A virus at 28 days of age (D28) with a booster at D49. Immune response to the vaccine is measured at D49, D56, D63, and D146 by serum levels of IAV-specific IgG and assays of hemagglutination inhibition (HAI). Analysis of the pre-vaccination microbiota characterized by 16S rRNA gene sequencing of fecal DNA reveals a higher vaccine response in piglets with a richer microbiota, and shows that 23 operational taxonomic units (OTUs) are differentially abundant between high and low IAV-specific IgG producers at D63. A stronger immune response is linked with OTUs assigned to the genus Prevotella and family Muribaculaceae, and a weaker response is linked with OTUs assigned to the genera Helicobacter and Escherichia-Shigella. A set of 81 OTUs accurately predicts IAV-specific IgG and HAI titer levels at all time points, highlighting early and late associations between pre-vaccination fecal microbiota composition and immune response to the vaccine.

scholarly journals Increased VEGF-A in solid type of lung adenocarcinoma reduces the patients’ survival

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Woon Yong Jung ◽  
Kyueng-Whan Min ◽  
Young Ha Oh
Keyword(s):  
Immune Response ◽  
Survival Analysis ◽  
Lung Adenocarcinoma ◽  
Survival Rates ◽  
Treatment Strategies ◽  
Enrichment Analysis ◽  
Genetic Alterations ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Solid Type

AbstractThe histological classification of lung adenocarcinoma includes 5 types: lepidic, acinar, papillary, micropapillary and solid. The complex gene interactions and anticancer immune response of these types are not well known. The aim of this study was to reveal the survival rates, genetic alterations and immune activities of the five histological types and provide treatment strategies. This study reviewed the histological findings of 517 patients with lung adenocarcinoma from The Cancer Genome Atlas (TCGA) database and classified them into five types. We performed gene set enrichment analysis (GSEA) and survival analysis according to the different types. We found six oncogenic gene sets that were higher in lung adenocarcinoma than in normal tissues. In the survival analysis of each type, the acinar type had a favorable prognosis, and the solid subtype had an unfavorable prognosis; however, the survival differences between the other types were not significant. Our study focused on the solid type, which had the poorest prognosis. The solid type was related to adaptive immune resistance associated with elevated CD8 T cells and high CD274 (encoding PD-L1) expression. In the pathway analyses, the solid type was significantly related to high vascular endothelial growth factor (VEGF)-A expression, reflecting tumor angiogenesis. Non-necrosis/low immune response affected by high VEGF-A was associated with worse prognosis. The solid type associated with high VEGF-A expression may contribute to the development of therapeutic strategies for lung adenocarcinoma.

scholarly journals Identification of long noncoding RNAs reveals the effects of dinotefuran on the brain in Apis mellifera (Hymenopptera: Apidae)

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Minjie Huang ◽  
Jie Dong ◽  
Haikun Guo ◽  
Minghui Xiao ◽  
Deqian Wang
Keyword(s):  
Immune Response ◽  
Honey Bee ◽  
Honey Bees ◽  
Transforming Growth Factor ◽  
Sublethal Effects ◽  
Inflammatory Responses ◽  
Noncoding Rnas ◽  
Enrichment Analysis ◽  
Long Noncoding Rnas ◽  
Gene Set Enrichment Analysis

Abstract Background Dinotefuran (CAS No. 165252–70-0), a neonicotinoid insecticide, has been used to protect various crops against invertebrate pests and has been associated with numerous negative sublethal effects on honey bees. Long noncoding RNAs (lncRNAs) play important roles in mediating various biological and pathological processes, involving transcriptional and gene regulation. The effects of dinotefuran on lncRNA expression and lncRNA function in the honey bee brain are still obscure. Results Through RNA sequencing, a comprehensive analysis of lncRNAs and mRNAs was performed following exposure to 0.01 mg/L dinotefuran for 1, 5, and 10 d. In total, 312 lncRNAs and 1341 mRNAs, 347 lncRNAs and 1458 mRNAs, and 345 lncRNAs and 1155 mRNAs were found to be differentially expressed (DE) on days 1, 5 and 10, respectively. Gene set enrichment analysis (GSEA) indicated that the dinotefuran-treated group showed enrichment in carbohydrate and protein metabolism and immune-inflammatory responses such as glycine, serine and threonine metabolism, pentose and glucuronate interconversion, and Hippo and transforming growth factor-β (TGF-β) signaling pathways. Moreover, the DE lncRNA TCONS_00086519 was shown by fluorescence in situ hybridization (FISH) to be distributed mainly in the cytoplasm, suggesting that it may serve as a competing endogenous RNA and a regulatory factor in the immune response to dinotefuran. Conclusion This study characterized the expression profile of lncRNAs upon exposure to neonicotinoid insecticides in young adult honey bees and provided a framework for further study of the role of lncRNAs in honey bee growth and the immune response.

scholarly journals Impact of Influenza A Virus Shutoff Proteins on Host Immune Responses

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 629
Author(s):  
Megan M. Dunagan ◽  
Kala Hardy ◽  
Toru Takimoto
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Influenza A Virus ◽  
Influenza A ◽  
Human Populations ◽  
Lymphocyte Migration ◽  
Host Immune Responses ◽  
Mhc Molecules ◽  
The Impact

Influenza A virus (IAV) is a significant human pathogen that causes seasonal epidemics. Although various types of vaccines are available, IAVs still circulate among human populations, possibly due to their ability to circumvent host immune responses. IAV expresses two host shutoff proteins, PA-X and NS1, which antagonize the host innate immune response. By transcriptomic analysis, we previously showed that PA-X is a major contributor for general shutoff, while shutoff active NS1 specifically inhibits the expression of host cytokines, MHC molecules, and genes involved in innate immunity in cultured human cells. So far, the impact of these shutoff proteins in the acquired immune response in vivo has not been determined in detail. In this study, we analyzed the effects of PA-X and NS1 shutoff activities on immune response using recombinant influenza A/California/04/2009 viruses containing mutations affecting the expression of shutoff active PA-X and NS1 in a mouse model. Our data indicate that the virus without shutoff activities induced the strongest T and B cell responses. Both PA-X and NS1 reduced host immune responses, but shutoff active NS1 most effectively suppressed lymphocyte migration to the lungs, antibody production, and the generation of IAV specific CD4+ and CD8+ T cells. NS1 also prevented the generation of protective immunity against a heterologous virus challenge. These data indicate that shutoff active NS1 plays a major role in suppressing host immune responses against IAV infection.

scholarly journals COVID-19 Mortality is Associated with Impaired Innate Immunity in Pre-existing Health Conditions

2021 ◽  
Author(s):  
Matthew E Lee ◽  
Yung Chang ◽  
Navid Ahmadinejad ◽  
Crista E Johnson-Agbakwu ◽  
Celeste Bailey ◽  
...  
Keyword(s):  
Risk Factors ◽  
Innate Immunity ◽  
Viral Infections ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Therapeutic Interventions ◽  
Health Conditions ◽  
Molecular Abnormalities ◽  
Hazard Ratios ◽  
Increased Risk

Background: COVID-19 poses a life-threatening endangerment to individuals with chronic diseases. However, not all comorbidities affect COVID-19 prognosis equally. Some increase the risk of COVID-19 related death by more than six folds while others show little to no impact. To prevent severe outcomes, it is critical that we comprehend pre-existing molecular abnormalities in common health conditions that predispose patients to poor prognoses. In this study, we aim to discover some of these molecular risk factors by associating gene expression dysregulations in common health conditions with COVID-19 mortality rates in different cohorts. Methods: We focused on fourteen pre-existing health conditions, for which age-and-sex-adjusted hazard ratios of COVID-19 mortality have been documented. For each health condition, we analyzed existing transcriptomics data to identify differentially expressed genes (DEGs) between affected individuals and unaffected individuals. We then tested if fold changes of any DEG in these pre-existing conditions were correlated with hazard ratios of COVID-19 mortality to discover molecular risk factors. We performed gene set enrichment analysis to identify functional groups overrepresented in these risk factor genes and examined their relationships with the COVID-19 disease pathway. Results: We found that upregulated expression of 70 genes and downregulated expression of 181 genes in pre-existing health conditions were correlated with increased risk of COVID-19 related death. These genes were significantly enriched with endoplasmic reticulum (ER) function, proinflammatory reaction, and interferon production that participate in viral transcription and immune responses to viral infections. Conclusions: Impaired innate immunity in pre-existing health conditions are associated with increased hazard of COVID-19 mortality. The discovered molecular risk factors are potential prognostic biomarkers and targets for therapeutic interventions.

scholarly journals MHV68 Latency Modulates the Host Immune Response to Influenza A Virus

Inflammation ◽  
2013 ◽  
Vol 36 (6) ◽  
pp. 1295-1303 ◽  
Author(s):  
Fumitake Saito ◽  
Toshihiro Ito ◽  
Judith M. Connett ◽  
Matthew A. Schaller ◽  
William F. Carson ◽  
...  
Keyword(s):  
Immune Response ◽  
Influenza A Virus ◽  
Influenza A ◽  
Host Immune Response

scholarly journals Response Modifiers: Tweaking the Immune Response Against Influenza A Virus

2019 ◽  
Vol 10 ◽  
Author(s):  
Husni Elbahesh ◽  
Thomas Gerlach ◽  
Giulietta Saletti ◽  
Guus F. Rimmelzwaan
Keyword(s):  
Immune Response ◽  
Influenza A Virus ◽  
Influenza A

scholarly journals Immunogenicity, Boostability, and Sustainability of the Immune Response after Vaccination against Influenza A Virus (H1N1) 2009 in a Healthy Population

2011 ◽  
Vol 18 (9) ◽  
pp. 1401-1405 ◽  
Author(s):  
Elisabeth Huijskens ◽  
John Rossen ◽  
Paul Mulder ◽  
Ruud van Beek ◽  
Hennie van Vugt ◽  
...  
Keyword(s):  
Immune Response ◽  
Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Virus H1n1 ◽  
Prospective Longitudinal Study ◽  
Virus Vaccination ◽  
Short Period ◽  
Prospective Longitudinal

ABSTRACTThe emergence of a new influenza A virus (H1N1) variant in 2009 led to a worldwide vaccination program, which was prepared in a relatively short period of time. This study investigated the humoral immunity against this virus before and after vaccination with a 2009 influenza A virus (H1N1) monovalent MF59-adjuvanted vaccine, as well as the persistence of vaccine-induced antibodies. Our prospective longitudinal study included 498 health care workers (mean age, 43 years; median age, 44 years). Most (89%) had never or only occasionally received a seasonal influenza virus vaccine, and 11% were vaccinated annually (on average, for >10 years). Antibody titers were determined by a hemagglutination inhibition (HI) assay at baseline, 3 weeks after the first vaccination, and 5 weeks and 7 months after the second vaccination. Four hundred thirty-five persons received two doses of the 2009 vaccine. After the first dose, 79.5% developed a HI titer of ≥40. This percentage increased to 83.3% after the second dose. Persistent antibodies were found in 71.9% of the group that had not received annual vaccinations and in 43.8% of the group that had received annual vaccinations. The latter group tended to have lower HI titers (P=0.09). With increasing age, HI titers decreased significantly, by 2.4% per year. A single dose of the 2009 vaccine was immunogenic in almost 80% of the study population, whereas an additional dose resulted in significantly increased titers only in persons over 50. Finally, a reduced HI antibody response against the 2009 vaccine was found in adults who had previously received seasonal influenza virus vaccination. More studies on the effect of yearly seasonal influenza virus vaccination on the immune response are warranted.

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