scholarly journals An Immunomodulatory Transcriptional Signature Associated With Persistent Listeria Infection in Hepatocytes

2021 ◽  
Vol 11 ◽  
Author(s):  
Natalie Descoeudres ◽  
Luc Jouneau ◽  
Céline Henry ◽  
Kevin Gorrichon ◽  
Aurélie Derré-Bobillot ◽  
...  
Keyword(s):  
Persistent Infection ◽  
Cholesterol Metabolism ◽  
Interferon Response ◽  
Type I ◽  
Sequencing Analysis ◽  
Immune Functions ◽  
Transcriptional Signature ◽  
Huh7 Cells ◽  
Primary Mouse

Listeria monocytogenes causes severe foodborne illness in pregnant women and immunocompromised individuals. After the intestinal phase of infection, the liver plays a central role in the clearance of this pathogen through its important functions in immunity. However, recent evidence suggests that during long-term infection of hepatocytes, a subpopulation of Listeria may escape eradication by entering a persistence phase in intracellular vacuoles. Here, we examine whether this long-term infection alters hepatocyte defense pathways, which may be instrumental for bacterial persistence. We first optimized cell models of persistent infection in human hepatocyte cell lines HepG2 and Huh7 and primary mouse hepatocytes (PMH). In these cells, Listeria efficiently entered the persistence phase after three days of infection, while inducing a potent interferon response, of type I in PMH and type III in HepG2, while Huh7 remained unresponsive. RNA-sequencing analysis identified a common signature of long-term Listeria infection characterized by the overexpression of a set of genes involved in antiviral immunity and the under-expression of many acute phase protein (APP) genes, particularly involved in the complement and coagulation systems. Infection also altered the expression of cholesterol metabolism-associated genes in HepG2 and Huh7 cells. The decrease in APP transcripts was correlated with lower protein abundance in the secretome of infected cells, as shown by proteomics, and also occurred in the presence of APP inducers (IL-6 or IL-1β). Collectively, these results reveal that long-term infection with Listeria profoundly deregulates the innate immune functions of hepatocytes, which could generate an environment favorable to the establishment of persistent infection.

scholarly journals The Type I Interferon Response Determines Differences in Choroid Plexus Susceptibility between Newborns and Adults in Herpes Simplex Virus Encephalitis

mBio ◽  
2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Douglas R. Wilcox ◽  
Stephen S. Folmsbee ◽  
William J. Muller ◽  
Richard Longnecker
Keyword(s):  
Choroid Plexus ◽  
Type I Interferon ◽  
Adult Brain ◽  
Interferon Response ◽  
Type I ◽  
Β Receptor ◽  
Simplex Virus ◽  
The Brain ◽  
Hsv 1

ABSTRACTNewborns are significantly more susceptible to severe viral encephalitis than adults, with differences in the host response to infection implicated as a major factor. However, the specific host signaling pathways responsible for differences in susceptibility and neurologic morbidity have remained unknown. In a murine model of HSV encephalitis, we demonstrated that the choroid plexus (CP) is susceptible to herpes simplex virus 1 (HSV-1) early in infection of the newborn but not the adult brain. We confirmed susceptibility of the CP to HSV infection in a human case of newborn HSV encephalitis. We investigated components of the type I interferon (IFN) response in the murine brain that might account for differences in cell susceptibility and found that newborns have a dampened interferon response and significantly lower basal levels of the alpha/beta interferon (IFN-α/β) receptor (IFNAR) than do adults. To test the contribution of IFNAR to restricting infection from the CP, we infected IFNAR knockout (KO) adult mice, which showed restored CP susceptibility to HSV-1 infection in the adult. Furthermore, reduced IFNAR levels did not account for differences we found in the basal levels of several other innate signaling proteins in the wild-type newborn and the adult, including protein kinase R (PKR), that suggested specific regulation of innate immunity in the developing brain. Viral targeting of the CP, a region of the brain that plays a critical role in neurodevelopment, provides a link between newborn susceptibility to HSV and long-term neurologic morbidity among survivors of newborn HSV encephalitis.IMPORTANCECompared to adults, newborns are significantly more susceptible to severe disease following HSV infection. Over half of newborn HSV infections result in disseminated disease or encephalitis, with long-term neurologic morbidity in 2/3 of encephalitis survivors. We investigated differences in host cell susceptibility between newborns and adults that contribute to severe central nervous system disease in the newborn. We found that, unlike the adult brain, the newborn choroid plexus (CP) was susceptible early in HSV-1 infection. We demonstrated that IFN-α/β receptor levels are lower in the newborn brain than in the adult brain and that deletion of this receptor restores susceptibility of the CP in the adult brain. The CP serves as a barrier between the blood and the cerebrospinal fluid and plays a role in proper neurodevelopment. Susceptibility of the newborn choroid plexus to HSV-1 has important implications in viral spread to the brain and, also, in the neurologic morbidity following HSV encephalitis.

scholarly journals Type-I interferon signatures in SARS-CoV-2 infected Huh7 cells

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Xi Chen ◽  
Elisa Saccon ◽  
K. Sofia Appelberg ◽  
Flora Mikaeloff ◽  
Jimmy Esneider Rodriguez ◽  
...  
Keyword(s):  
Immune Responses ◽  
Type I Interferon ◽  
Innate Immune ◽  
Interferon Response ◽  
Type I ◽  
Response Type ◽  
Innate Immune Responses ◽  
Interferon Stimulated Genes ◽  
Huh7 Cells ◽  
Related Proteins

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes Coronavirus disease 2019 (COVID-19) has caused a global health emergency. A key feature of COVID-19 is dysregulated interferon-response. Type-I interferon (IFN-I) is one of the earliest antiviral innate immune responses following viral infection and plays a significant role in the pathogenesis of SARS-CoV-2. In this study, using a proteomics-based approach, we identified that SARS-CoV-2 infection induces delayed and dysregulated IFN-I signaling in Huh7 cells. We demonstrate that SARS-CoV-2 is able to inhibit RIG-I mediated IFN-β production. Our results also confirm the recent findings that IFN-I pretreatment is able to reduce the susceptibility of Huh7 cells to SARS-CoV-2, but not post-treatment. Moreover, senescent Huh7 cells, in spite of showing accentuated IFN-I response were more susceptible to SARS-CoV-2 infection, and the virus effectively inhibited IFIT1 in these cells. Finally, proteomic comparison between SARS-CoV-2, SARS-CoV, and MERS-CoV revealed a distinct differential regulatory signature of interferon-related proteins emphasizing that therapeutic strategies based on observations in SARS-CoV and MERS-CoV should be used with caution. Our findings provide a better understanding of SARS-CoV-2 regulation of cellular interferon response and a perspective on its use as a treatment. Investigation of different interferon-stimulated genes and their role in the inhibition of SARS-CoV-2 pathogenesis may direct novel antiviral strategies.

scholarly journals Cell-mediated transmission of human T cell lymphotropic virus type I to human malignant trophoblastic cells results in long-term persistent infection

1995 ◽  
Vol 76 (1) ◽  
pp. 167-173 ◽  
Author(s):  
X. Liu ◽  
V. Zachar ◽  
N. Norskov-Lauritsen ◽  
G. Aboagye-Mathiesen ◽  
M. Zdravkovic ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Persistent Infection ◽  
Type I ◽  
Trophoblastic Cells ◽  
Human T Cell

scholarly journals Interplay of Acute and Persistent Infections Caused by Venezuelan Equine Encephalitis Virus Encoding Mutated Capsid Protein

2010 ◽  
Vol 84 (19) ◽  
pp. 10004-10015 ◽  
Author(s):  
Svetlana Atasheva ◽  
Valentina Krendelchtchikova ◽  
Anton Liopo ◽  
Elena Frolova ◽  
Ilya Frolov
Keyword(s):  
Capsid Protein ◽  
Virus Replication ◽  
Persistent Infection ◽  
Venezuelan Equine Encephalitis Virus ◽  
Encephalitis Virus ◽  
Type I ◽  
Venezuelan Equine Encephalitis ◽  
Antiviral State ◽  
Equine Encephalitis Virus

ABSTRACT Venezuelan equine encephalitis virus (VEEV) is a significant human and animal pathogen. The highlight of VEEV replication in vitro, in cells of vertebrate origin, is the rapid development of cytopathic effect (CPE), which is strongly dependent upon the expression of viral capsid protein. Besides being an integral part of virions, the latter protein is capable of (i) binding both the nuclear import and nuclear export receptors, (ii) accumulating in the nuclear pore complexes, (iii) inhibiting nucleocytoplasmic trafficking, and (iv) inhibiting transcription of cellular ribosomal and messenger RNAs. Using our knowledge of the mechanism of VEEV capsid protein function in these processes, we designed VEEV variants containing combinations of mutations in the capsid-coding sequences. These mutations made VEEV dramatically less cytopathic but had no effect on infectious virus production. In cell lines that have defects in type I interferon (IFN) signaling, the capsid mutants demonstrated very efficient persistent replication. In other cells, which have no defects in IFN production or signaling, the same mutants were capable of inducing a long-term antiviral state, downregulating virus replication to an almost undetectable level. However, ultimately, these cells also developed a persistent infection, characterized by continuous virus replication and beta IFN (IFN-β) release. The results of this study demonstrate that the long-term cellular antiviral state is determined by the synergistic effects of type I IFN signaling and the antiviral reaction induced by replicating viral RNA and/or the expression of VEEV-specific proteins. The designed mutants represent an important model for studying the mechanisms of cell interference with VEEV replication and development of persistent infection.

scholarly journals Type-I interferon signatures in SARS-CoV-2 infected Huh7 cells

2021 ◽  
Author(s):  
Xi Chen ◽  
Elisa Saccon ◽  
K. Sofia Appelberg ◽  
Flora Mikaeloff ◽  
Jimmy Esneider Rodriguez ◽  
...  
Keyword(s):  
Immune Responses ◽  
Type I Interferon ◽  
Innate Immune ◽  
Interferon Response ◽  
Type I ◽  
Response Type ◽  
Innate Immune Responses ◽  
Interferon Stimulated Genes ◽  
Huh7 Cells ◽  
Related Proteins

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes Coronavirus disease 2019 (COVID-19) has caused a global health emergency. A key feature of COVID-19 is dysregulated interferon-response. Type-I interferon (IFN-I) is one of the earliest antiviral innate immune responses following viral infection and plays a significant role in the pathogenesis of SARS-CoV-2. In this study, using a proteomics-based approach, we identified that SARS-CoV-2 infection induces delayed and dysregulated IFN-I signaling in Huh7 cells. We demonstrate that SARS-CoV-2 is able to inhibit RIG-I mediated IFN-β production. Our results also confirm the recent findings that IFN-I pretreatment is able to reduce susceptibility of Huh7 cells to SARS-CoV-2, but not post-treatment. Moreover, senescent Huh7 cells, in spite of showing accentuated IFN-I response were more susceptible to SARS-CoV-2 infection, and the virus effectively inhibited IFIT1 in these cells. Finally, proteomic comparison between SARS-CoV-2, SARS-CoV and MERS-CoV revealed a distinct differential regulatory signature of interferon-related proteins emphasizing that therapeutic strategies based on observations in SARS-CoV and MERS-CoV should be used with caution. Our findings provide a better understanding of SARS-CoV-2 regulation of cellular interferon response and a perspective on its use as a treatment. Investigation of different interferon stimulated genes and their role in inhibition of SARS-CoV-2 pathogenesis may direct novel antiviral strategies.

Molecular Characterization of a Type I Quantitative Factor V Deficiency in a Thrombosis Patient that Is “Pseudo Homozygous” for Activated Protein C Resistance

1997 ◽  
Vol 77 (02) ◽  
pp. 252-257 ◽  
Author(s):  
Joan F Guasch ◽  
Ruud P M Lensen ◽  
Rogier M Bertina
Keyword(s):  
Protein C ◽  
Dna Analysis ◽  
Activated Protein C ◽  
Type I ◽  
Factor V ◽  
Sequencing Analysis ◽  
Apc Resistance ◽  
Quantitative Factor ◽  
Factor V Deficiency ◽  
Fv Leiden

SummaryResistance to activated protein C (APC), which is associated with the FV Leiden mutation in the large majority of the cases, is the most common genetic risk factor for thrombosis. Several laboratory tests have been developed to detect the APC-resistance phenotype. The result of the APC-resistance test (APC-sensitivity ratio, APC-SR) usually correlates well with the FV Leiden genotype, but recently some discrepancies have been reported. Some thrombosis patients that are heterozygous for FV Leiden show an APC-SR usually found only in homozygotes for the defect. Some of those patients proved to be compound heterozygotes for the FV Leiden mutation and for a type I quantitative factor V deficiency. We have investigated a thrombosis patient characterized by an APC-SR that would predict homozygosity for FV Leiden. DNA analysis showed that he was heterozygous for the mutation. Sequencing analysis of genomic DNA revealed that the patient also is heterozygous for a G5509→A substitution in exon 16 of the factor V gene. This mutation interferes with the correct splicing of intron 16 and leads to the presence of a null allele, which corresponds to the “non-FV Leiden” allele. The conjunction of these two defects in the patient apparently leads to the same phenotype as observed in homozygotes for the FV Leiden mutation.

Comparative Study of effectiveness of mobilization with movement (MWM) and End range mobilization (ERM) techniques in frozen shoulder

2018 ◽  
Vol 4 (4) ◽  
pp. 519-522
Author(s):  
Jeyakumar S ◽  
Jagatheesan Alagesan ◽  
T.S. Muthukumar
Keyword(s):  
Range Of Motion ◽  
Frozen Shoulder ◽  
Type I ◽  
Mean Values ◽  
Functional Activities ◽  
Group A ◽  
The Mean ◽  
Group B

Background: Frozen shoulder is disorder of the connective tissue that limits the normal Range of motion of the shoulder in diabetes, frozen shoulder is thought to be caused by changes to the collagen in the shoulder joint as a result of long term Hypoglycemia. Mobilization is a therapeutic movement of the joint. The goal is to restore normal joint motion and rhythm. The use of mobilization with movement for peripheral joints was developed by mulligan. This technique combines a sustained application of manual technique “gliding” force to the joint with concurrent physiologic motion of joint, either actively or passively. This study aims to find out the effects of mobilization with movement and end range mobilization in frozen shoulder in Type I diabetics. Materials and Methods: 30 subjects both male and female, suffering with shoulder pain and clinically diagnosed with frozen shoulder was recruited for the study and divided into two groups with 15 patients each based on convenient sampling method. Group A patients received mobilization with movement and Group B patients received end range mobilization for three weeks. The outcome measurements were SPADI, Functional hand to back scale, abduction range of motion using goniometer and VAS. Results: The mean values of all parameters showed significant differences in group A as compared to group B in terms of decreased pain, increased abduction range and other outcome measures. Conclusion: Based on the results it has been concluded that treating the type 1 diabetic patient with frozen shoulder, mobilization with movement exercise shows better results than end range mobilization in reducing pain and increase functional activities and mobility in frozen shoulder.

Effects of long-term optimization and short-term deterioration of glycemic control on glucose counterregulation in type I diabetes mellitus

Diabetes ◽  
1984 ◽  
Vol 33 (4) ◽  
pp. 394-400 ◽  
Author(s):  
G. Bolli ◽  
P. De Feo ◽  
S. De Cosmo ◽  
G. Perriello ◽  
G. Angeletti ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Glycemic Control ◽  
Type I Diabetes ◽  
Type I Diabetes Mellitus ◽  
Type I ◽  
Short Term

PLASMACYTOID DENDRITIC CELLS FUNCTION IN HIV INFECTION

2008 ◽  
Vol 31 (4) ◽  
pp. 13
Author(s):  
Martin Hyrcza ◽  
Mario Ostrowski ◽  
Sandy Der
Keyword(s):  
Dendritic Cells ◽  
Influenza Virus ◽  
Hiv Infection ◽  
Gene Transcription ◽  
Sendai Virus ◽  
Plasmacytoid Dendritic Cells ◽  
Type I Interferons ◽  
Interferon Response ◽  
Type I ◽  
Type I Ifn

Plasmacytoid dendritic cells (pDCs) are innate immune cells able to produce large quantities of type I interferons (IFN) when activated. Human immunodeficiency virus (HIV)-infected patients show generalized immune dysfunction characterized in part by chronic interferon response. In this study we investigated the role of dendritic cells inactivating and maintaining this response. Specifically we compared the IFN geneactivity in pDCs in response to several viruses and TLR agonists. We hypothesized that 1) the pattern of IFN gene transcription would differ in pDCs treated with HIV than with other agents, and 2) that pDCs from patients from different stages of disease would respond differently to the stimulations. To test these hypotheses, we obtained pDCs from 15 HIV-infected and uninfected individuals and treated freshly isolated pDCs with either HIV (BAL strain), influenza virus (A/PR/8/34), Sendai virus (Cantell strain), TLR7 agonist(imiquimod), or TLR9 agonist (CpG-ODN) for 6h. Type I IFN gene transcription was monitored by real time qPCRfor IFNA1, A2, A5, A6, A8,A17, B1, and E1, and cytokine levels were assayed by Cytometric Bead Arrays forTNF?, IL6, IL8, IL10, IL1?, and IL12p70. pDC function as determined by these two assays showed no difference between HIV-infected and uninfected patients or between patients with early or chronic infection. Specifically, HIV did notinduce type I IFN gene expression, whereas influenza virus, Sendai virus and imiquimod did. Similarly, HIV failed to induce any cytokine release from pDCs in contrast to influenza virus, Sendai virus and imiquimod, which stimulatedrelease of TNF?, IL6, or IL8. Together these results suggest that the reaction of pDCs to HIV virus is quantitatively different from the response to agents such as virus, Sendai virus, and imiquimod. In addition, pDCs from HIV-infected persons have responses similar to pDCs from uninfected donors, suggesting, that the DC function may not be affected by HIV infection.

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