Accelerated Prion Replication in, but Prolonged Survival Times of, Prion-Infected CXCR3−/− Mice

ABSTRACT Prion diseases have a significant inflammatory component. Glia activation, which is associated with increased production of cytokines and chemokines, may play an important role in disease development. Among the chemokines upregulated highly and early upregulated during scrapie infections are ligands of CXCR3. To gain more insight into the role of CXCR3 in a prion model, CXCR3-deficient (CXCR3−/−) mice were infected intracerebrally with scrapie strain 139A and characterized in comparison to similarly infected wild-type controls. CXCR3−/− mice showed significantly prolonged survival times of up to 30 days on average. Surprisingly, however, they displayed accelerated accumulation of misfolded proteinase K-resistant prion protein PrPSc and 20 times higher infectious prion titers than wild-type mice at the asymptomatic stage of the disease, indicating that these PrP isoforms may not be critical determinants of survival times. As demonstrated by immunohistochemistry, Western blotting, and gene expression analysis, CXCR3-deficient animals develop an excessive astrocytosis. However, microglia activation is reduced. Quantitative analysis of gliosis-associated gene expression alterations demonstrated reduced mRNA levels for a number of proinflammatory factors in CXCR3−/− compared to wild-type mice, indicating a weaker inflammatory response in the knockout mice. Taken together, this murine prion model identifies CXCR3 as disease-modifying host factor and indicates that inflammatory glial responses may act in concert with PrPSc in disease development. Moreover, the results indicate that targeting CXCR3 for treatment of prion infections could prolong survival times, but the results also raise the concern that impairment of microglial migration by ablation or inhibition of CXCR3 could result in increased accumulation of misfolded PrPSc.

Download Full-text

Effect of Heme Oxygenase-1 Overexpression in Two Models of Lung Inflammation

Experimental Biology and Medicine ◽

10.1177/15353702-0322805-02 ◽

2003 ◽

Vol 228 (5) ◽

pp. 442-446 ◽

Cited By ~ 49

Author(s):

A. Zampetaki ◽

T. Minamino ◽

S.A. Mitsialis ◽

S. Kourembanas

Keyword(s):

Transgenic Mice ◽

Heme Oxygenase ◽

Lung Inflammation ◽

Heme Oxygenase 1 ◽

Mrna Levels ◽

Wild Type ◽

Pronounced Increase ◽

Protein Levels ◽

Cytokines And Chemokines ◽

Genetically Engineered Mice

An increasing number of studies implicate heme oxygenase-1 (HO-1) in the regulation of inflammation. Although the mechanisms involved in this cytoprotection are largely unknown, HO-1 and its enzymatic products, carbon monoxide and bilirubin, downregulate the inflammatory response by either attenuating the expression of adhesion molecules and thus inhibiting leukocyte recruitment or by repressing the induction of cytokines and chemokines. In the present study we used genetically engineered mice that express high levels of a human cDNA HO-1 transgene in lung epithelium to assess the effect of HO-1 on lung inflammation. Two separate models of inflammation were studied: hypoxic exposure and lipopolysaccharide (LPS) challenge. We found that both mRNA and protein levels of specific cytokines and chemokines were significantly elevated in response to hypoxia in the lungs of wild-type mice after 2 and 5 days of exposure but significantly suppressed in the hypoxic lungs of transgenic mice, suggesting that inhibition of these cytokines was caused by overexpression of HO-1. However, LPS treatment resulted in a very pronounced increase in mRNA levels of several cytokines in both wild-type and transgenic mice. Despite the high mRNA levels, significantly lower cytokine protein levels were detected in the bronchoalveolar lavage of HO-1 overexpressing mice compared with wild type, indicating that HO-1 leads to repression of cytokines in the airway. These results demonstrate that HO-1 activity operates through distinct molecular mechanisms to confer cytoprotection in the hypoxic and the LPS models of inflammation.

Download Full-text

Effect of LCR 5′HS4 and 5′HS1 Deletions on β-Like Globin Gene Expression in β-Yac Transgenic Mice.

Blood ◽

10.1182/blood.v104.11.1209.1209 ◽

2004 ◽

Vol 104 (11) ◽

pp. 1209-1209

Author(s):

Susanna Harju ◽

Halyna Fedosyuk ◽

Kenneth R. Peterson

Keyword(s):

Gene Expression ◽

Homologous Recombination ◽

Globin Gene ◽

Developmental Expression ◽

Mrna Levels ◽

Wild Type ◽

Rnase Protection ◽

Transgenic Lines ◽

Definitive Erythropoiesis ◽

Globin Gene Expression

Abstract A 213 Kb human β-globin locus yeast artificial chromosome (β-YAC) was modified by homologous recombination to delete 2.9 Kb of cross-species conserved sequence similarity encompassing the LCR 5′HS4 (Δ5′HS4 β-YAC). Three transgenic mouse lines were established; each contained two intact copies of the β-globin locus as determined by long range restriction enzyme mapping (LRRM) and Southern blot hybridization analyses. Human ε-, γ- and β-globin, and mouse α- and ζ-globin mRNAs were measured by RNAse protection in hematopoietic tissues derived from staged embryos, fetuses and adult mice. No difference in the temporal pattern of globin transgene expression was observed between Δ5′HS4 β-YAC mice and wild-type β-YAC mice. In addition, quantitative per-copy human β-like globin mRNA levels were similar between Δ5′HS4 and wild-type β-YAC transgenic lines, although γ-globin gene expression was slightly increased in the fetal liver, while β-globin gene expression was slightly decreased in Δ5′HS4 β-YAC mice. These data are in contrast to data obtained from β-YAC mice containing a deletion of the 280 bp 5′HS4 core. In these mice, γ- and β-globin gene expression was significantly decreased during fetal definitive erythropoiesis and β-globin gene expression was decreased during adult definitive erythropoiesis. However, these data are consistent with the observation that deletion of the 5′HS core elements is more deleterious than large deletions of the 5′HSs. Together, the compiled deletion data supports the hypothesis that the LCR exists as a holocomplex in which the 5′HS cores form an active site and the flanking 5′HS regions constrain the holocomplex conformation. In this model, 5′HS core mutations are dominant negative, whereas larger deletions allow the LCR to fold into alternate holocomplex structures that function normally, albeit less efficiently. To complete the study on the contribution of the individual 5′HSs to LCR function, a 0.8 Kb 5′HS1 fragment was deleted in the 213 Kb β-YAC by homologous recombination. Two ΔHS1 β-YAC transgenic lines have been established; four additional founders were recently identified. Of the two lines, one contains two intact copies of the globin locus; the other contains four deleted copies, one of which extends from the LCR through just 5′ to the β-globin gene. For both lines, ε-globin gene expression was markedly reduced, approximately 5–10 fold, during primitive erythropoiesis. Developmental expression profiles and levels of the γ- and β-globin genes (in the line that contains loci including the β-globin gene) were unaffected by deletion of 5′HS1. Breeding of the remaining four founders to obtain F1 and F2 progeny for similar structure/function studies is in progress. Decreased expression of the β-globin gene is the first phenotype ascribed to a 5′HS1 mutation, suggesting that this HS does indeed have a role in LCR function.

Download Full-text

A Targeted Resequencing Study Allows the Detection of a Common Polymorphism At Mirna-223 Binding Site in 3′Untranslated Region Which Deregulates HSP90B1 Expression in Chronic Lymphocytic Leukemia

Blood ◽

10.1182/blood.v120.21.1776.1776 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1776-1776

Author(s):

Ana E Rodríguez ◽

Dalia Qwaider ◽

Rocío Benito ◽

Irena Misiewicz-Krzeminska ◽

María Hernández-Sánchez ◽

...

Keyword(s):

Gene Expression ◽

Binding Site ◽

Cell Line ◽

B Lymphocytes ◽

Prognostic Significance ◽

Mrna Levels ◽

Healthy Controls ◽

Wild Type ◽

Single Nucleotide ◽

Custom Made

Abstract Abstract 1776 Array-based sequence capture (Roche NimbleGen) followed by next-generation sequencing (Roche GS FLX Titanium sequencing platform) was used to analyze genetic variations in 93 genes relevant in CLL and two chromosomal regions: 13q14.3 and 17p13.1. CD19+ cells from 4 patients with CLL and 4 patients with other hematological malignancies (used as controls) were studied. A custom-made data analysis pipeline was used to annotate detected variants, including known single-nucleotide polymorphisms (SNPs), amino acid consequences, genomic location and miRNA binding sites. The enrichment assay followed by NGS allowed the detection of over 1600 variations/sample (median 1721, range 1618–1823). All putative variants were first compared with published single nucleotide polymorphism (SNP) data (dbSNP build 130) and most of the variants detected were identified as known SNPs. Overall, 10% of variants detected in each sample were variations not previously described. Interestingly, a 4bp insertion/deletion polymorphism (rs2307842) in the 3′UTR of HSP90B1, target site for miR-223, was detected. There is an increasing evidence suggesting that SNPs in the 3′UTR targeted by miRNAs (known as miRSNPs) are associated with diseases by affecting gene expression. We hypothesized that this ‘GACT’ deletion disrupts the binding site for miR-223 thereby increasing the translation of HSP90B1 and we confirmed that miR-223 regulates HSP90B1 expression by 3′UTR reporter assays. The relative luciferase activity of the construct with wild-type 3′UTR (WT-3′UTR) was significantly repressed by 31% following miR-223 transfection (p<0.05). However, the presence of rs2307842 polymorphism in 3′UTR of HSP90B1 (VAR-3′UTR) abolished this suppression, suggesting that miR-223 directly binds to this site. We also validated HSP90B1 as a target gene of miR223 by transfecting MM1S and H929 cell lines with miR-223/NC mimics and then measuring HSP90B1 expression by semi-quantitative PCR and Western blot. Exogenous expression of miR-223 downregulated the expression levels of HSP90B1 in H929 cell line (WT-3′UTR) in both mRNA (p<0.05) and protein levels. By contrast, HSP90B1 expression was not modified in MM1S cell line (VAR-3′UTR). To evaluate the clinical impact of HSP90B1 3′UTR polymorphism, we expanded the study to 109 additional patients with CLL and 32 healthy controls. Sequencing of the HSP90B1 3′UTR region was performed by pyrosequencing (PyroMark Q24 system, Qiagen). The rs2307842 was detected in 27/109 (25%) patients and 8/32 (25%) healthy controls, as expected. Overall, we did not find any significant relationship between rs2307842 and clinical characteristics of CLL patients. To gain insight into its influence on gene expression, we measured HSP90B1 mRNA levels in paired samples (tumoral and normal) from CLL patients with rs2307842 (VAR-CLLs, n=6) and wild-type (WT-CLLs, n=12). PCR results showed that B lymphocytes (tumoral fraction) from VAR-CLLs have a higher expression of HSP90B1 than B lymphocytes from WT-CLLs (P=0.002) and also from the normal cells of the same patients (VAR-CLLs) (P=0.011). However, in WT-CLLs, no changes in mRNA expression were observed between tumor and normal fractions, being HSP90B1 mRNA levels similar to the normal fraction of VAR-CLLs. Thus, rs2307842 determined HSP90B1 overexpression only in the tumor fraction of the CLL patients with the polymorphism. Downregulation of miR-223 has prognostic significance in CLL. However, there is no evidence of the pathogenetic mechanism of this miRNA in CLL patients, and no target has been proposed or validated for miR-223 in CLL until date. Thus, this work provides novel information about how the downregulation of miR-223 can be determining the poor outcome of CLL patients, maybe through upregulation of HSP90B1 expression. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Tight Control of Respiration by NADH Dehydrogenase ND5 Subunit Gene Expression in Mouse Mitochondria

Molecular and Cellular Biology ◽

10.1128/mcb.20.3.805-815.2000 ◽

2000 ◽

Vol 20 (3) ◽

pp. 805-815 ◽

Cited By ~ 90

Author(s):

Yidong Bai ◽

Rebecca M. Shakeley ◽

Giuseppe Attardi

Keyword(s):

Gene Expression ◽

Nadh Dehydrogenase ◽

Mrna Level ◽

Mouse Cell ◽

Synthesis Rate ◽

Mrna Levels ◽

Wild Type ◽

Normal Number ◽

Nd5 Gene ◽

Cell Variant

ABSTRACT A mouse cell variant carrying in heteroplasmic form a nonsense mutation in the mitochondrial DNA-encoded ND5 subunit of the respiratory NADH dehydrogenase has been isolated and characterized. The derivation from this mutant of a large number of cell lines containing between 4 and 100% of the normal number of wild-type ND5 genes has allowed an analysis of the genetic and functional thresholds operating in mouse mitochondria. In wild-type cells, ∼40% of the ND5 mRNA level was in excess of that required for ND5 subunit synthesis. However, in heteroplasmic cells, the functional mRNA level decreased in proportion to the number of wild-type ND5 genes over a 25-fold range, pointing to the lack of any compensatory increase in rate of transcription and/or stability of mRNA. Most strikingly, the highest ND5 synthesis rate was just sufficient to support the maximum NADH dehydrogenase-dependent respiration rate, with no upregulation of translation occurring with decreasing wild-type mRNA levels. These results indicate that, despite the large excess of genetic potential of the mammalian mitochondrial genome, respiration is tightly regulated by ND5 gene expression.

Download Full-text

Increased plasma non-esterified fatty acids and platelet-activating factor acetylhydrolase are associated with susceptibility to atherosclerosis in mice

Clinical Science ◽

10.1042/cs20030375 ◽

2004 ◽

Vol 106 (4) ◽

pp. 421-432 ◽

Cited By ~ 30

Author(s):

Uma SINGH ◽

Shumei ZHONG ◽

Momiao XIONG ◽

Tong-bin LI ◽

Allan SNIDERMAN ◽

...

Keyword(s):

Gene Expression ◽

Fatty Acids ◽

Animal Models ◽

Enzyme Activities ◽

Platelet Activating Factor ◽

Density Lipoprotein ◽

Mrna Levels ◽

Wild Type ◽

Platelet Activating Factor Acetylhydrolase ◽

Esterified Fatty Acids

Animal models provide vital tools to explicate the pathogenesis of atherosclerosis. Accordingly, we established two atherosclerosis-prone mice models: (i) mice lacking the LDL (low-density lipoprotein) receptor (LDLR) and the ability to edit apo (apolipoprotein) B mRNA (Apobec1; designated LDb: LDLR-/-Apobec1-/-), and (ii) mice with the LDb background, who also overexpressed human apoB100 (designated LTp: LDLR-/-Apobec1-/-ERhB+/+). Both LDb and LTp mice had markedly elevated levels of LDL and increased levels of NEFAs (non-esterified fatty acids) compared with C57BL/6 wild-type mice. However, fasting glucose and insulin levels in both animals were not different than those in C57BL/6 wild-type mice. It has been suggested that PAF-AH (platelet-activating factor acetylhydrolase) increases susceptibility to vascular disease. Both LDb and LTp mice had significantly higher PAF-AH mRNA levels compared with C57BL/6 wild-type mice. PAF-AH gene expression was also significantly influenced by age and sex. Interestingly, PAF-AH mRNA levels were significantly higher in both LTp male and female mice than in the LDb mice. This increased PAF-AH gene expression was associated with elevated plasma PAF-AH enzyme activities (LTp>LDb>C57BL/6). Moreover, a greater proportion of PAF-AH activity was associated with the apoB-containing lipoproteins: 29% in LTp and 13% in LDb mice compared with C57BL/6 wild-type animals (6.7%). This may explain why LTp mice developed more atherosclerotic lesions than LDb mice by 8 months of age. In summary, increased plasma NEFAs, PAF-AH mRNA and enzyme activities are associated with accelerated atherogenesis in these animal models.

Download Full-text

Induction of mucin gene expression in human colonic cell lines by PMA is dependent on PKC-ε

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1999.277.5.g1041 ◽

1999 ◽

Vol 277 (5) ◽

pp. G1041-G1047 ◽

Cited By ~ 12

Author(s):

D.-H. Hong ◽

G. Petrovics ◽

W. B. Anderson ◽

J. Forstner ◽

G. Forstner

Keyword(s):

Gene Expression ◽

Cell Lines ◽

Dominant Negative ◽

Mrna Levels ◽

Wild Type ◽

Mucin Gene ◽

Time Period ◽

Mucin Expression ◽

Mucin Genes

Treatment of HT-29 cells with phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC), induces MUC2 expression. To investigate the role of PKC in regulating mucin genes in intestinal cells, we examined the regulation of MUC1, MUC2, MUC5AC, MUC5B, and MUC6 expression in two human mucin-producing colonic cell lines, T84 and HT29/A1. T84 and HT29/A1 cells (at 80–90% confluency) were exposed to 100 nM PMA for 0, 3, and 6 h. Twofold or greater increases in mRNA levels for MUC2 and MUC5AC were observed in both cell lines during this time period, whereas the levels of MUC1, MUC5B, and MUC6 mRNAs were only marginally affected. These results indicated that PKC differentially regulates mucin gene expression and that it may be responsible for altered mucin expression. Our previous results suggested that the Ca2+-independent PKC-ε isoform appeared to mediate PMA-regulated mucin exocytosis in these cell lines. To determine if PKC-ε was also involved in MUC2/MUC5AC gene induction, HT29/A1 cells were stably transfected with either a wild-type PKC-ε or a dominant-negative ATP-binding mutant of PKC-ε (PKC-ε K437R). Overexpression of the dominant-negative PKC-ε K437R blocked induction of both mucin genes, whereas PMA-induced mucin gene expression was not prevented by overexpression of wild-type PKC-ε. PMA-dependent MUC2 mucin secretion was also blocked in cells overexpressing the dominant-negative PKC-ε K437R. On the basis of these observations, PKC-ε appears to mediate the expression of two major gastrointestinal mucins in response to PMA as well as PMA-regulated mucin exocytosis.

Download Full-text

A Redox-Responsive Regulator of Photosynthesis Gene Expression in the Cyanobacterium Synechocystis sp. Strain PCC 6803

Journal of Bacteriology ◽

10.1128/jb.182.15.4268-4277.2000 ◽

2000 ◽

Vol 182 (15) ◽

pp. 4268-4277 ◽

Cited By ~ 100

Author(s):

Hong Li ◽

Louis A. Sherman

Keyword(s):

Gene Expression ◽

Reaction Center ◽

D1 Protein ◽

Insertion Mutation ◽

Mrna Levels ◽

Related Gene ◽

Wild Type ◽

Unicellular Cyanobacterium ◽

Redox Poise ◽

Pcc 6803

ABSTRACT We have identified genes in the unicellular cyanobacteriumSynechocystis sp. strain PCC 6803 that are involved with redox control of photosynthesis and pigment-related genes. The genes,rppA (sll0797) and rppB (sll0798), represent a two-component regulatory system that controls the synthesis of photosystem II (PSII) and PSI genes, in addition to photopigment-related genes. rppA (regulator of photosynthesis- and photopigment-related gene expression) andrppB exhibit strong sequence similarity to prokaryotic response regulators and histidine kinases, respectively. In the wild type, the steady-state mRNA levels of PSII reaction center genes increased when the plastoquinone (PQ) pool was oxidized and decreased when the PQ pool was reduced, whereas transcription of the PSI reaction center genes was affected in an opposite fashion. Such results suggested that the redox poise of the PQ pool is critical for regulation of the photosystem reaction center genes. In ΔrppA, an insertion mutation of rppA, the PSII gene transcripts were highly up-regulated relative to the wild type under all redox conditions, whereas transcription of phycobilisome-related genes and PSI genes was decreased. The higher transcription of the psbA gene in ΔrppA was manifest by higher translation of the D1 protein and a concomitant increase in O2 evolution. The results demonstrated that RppA is a regulator of photosynthesis- and photopigment-related gene expression, is involved in the establishment of the appropriate stoichiometry between the photosystems, and can sense changes in the PQ redox poise.

Download Full-text

Organ-Specific Role of MyD88 for Gene Regulation during Polymicrobial Peritonitis

Infection and Immunity ◽

10.1128/iai.01681-05 ◽

2006 ◽

Vol 74 (6) ◽

pp. 3618-3632 ◽

Cited By ~ 12

Author(s):

Heike Weighardt ◽

Jörg Mages ◽

Gabriela Jusek ◽

Simone Kaiser-Moore ◽

Roland Lang ◽

...

Keyword(s):

Gene Expression ◽

Transcriptional Activation ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Dependent Manner ◽

Wild Type ◽

Cytokines And Chemokines ◽

Organ Specific ◽

Deficient Mice

ABSTRACT Sepsis leads to the rapid induction of proinflammatory signaling cascades by activation of the innate immune system through Toll-like receptors (TLR). To characterize the role of TLR signaling through MyD88 for sepsis-induced transcriptional activation, we investigated gene expression during polymicrobial septic peritonitis by microarray analysis. Comparison of gene expression profiles for spleens and livers from septic wild-type and MyD88-deficient mice revealed striking organ-specific differences. Whereas MyD88 deficiency strongly reduced sepsis-induced gene expression in the liver, gene expression in the spleen was largely independent of MyD88, indicating organ-specific transcriptional regulation during polymicrobial sepsis. In addition to genes regulated by MyD88 in an organ-dependent manner, we also identified genes that exhibited an organ-independent influence of MyD88 and mostly encoded cytokines and chemokines. Notably, the expression of interferon (IFN)-regulated genes was markedly increased in septic MyD88-deficient mice compared to that in septic wild-type controls. Expression of IFN-regulated genes was dependent on the adapter protein TRIF. These results suggest that the influence of MyD88 on gene expression during sepsis strongly depends on the organ compartment affected by inflammation and that the lack of MyD88 may lead to disbalance of the expression of IFN-regulated genes.

Download Full-text

SARS-CoV-2 variants of concern infect the respiratory tract and induce inflammatory response in wild-type laboratory mice

10.1101/2021.09.29.462373 ◽

2021 ◽

Author(s):

Shannon Stone ◽

Hussin A. Rothan ◽

Janhavi P. Natekar ◽

Pratima Kumari ◽

Shaligram Sharma ◽

...

Keyword(s):

Immune Escape ◽

Mrna Levels ◽

Laboratory Mice ◽

Wild Type ◽

The Public ◽

Cytokines And Chemokines ◽

Tnf Α ◽

New Hosts ◽

High Concentrations ◽

Old Mice

AbstractThe emergence of new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern poses a major threat to the public health due to possible enhanced virulence, transmissibility and immune escape. These variants may also adapt to new hosts in part through mutations in the spike protein. In this study, we evaluated the infectivity and pathogenicity of SARS-CoV-2 variants of concern in wild-type C57BL/6 mice. Six-week-old mice were inoculated intranasally with a representative virus from the original B.1 lineage or emerging B.1.1.7 and B.1.351 lineages. We also infected a group of mice with a mouse-adapted SARS-CoV-2 (MA10). Viral load and mRNA levels of multiple cytokines and chemokines were analyzed in the lung tissues on day 3 after infection. Our data show that unlike the B.1 virus, the B.1.1.7 and B.1.351 viruses are capable of infecting C57BL/6 mice and replicating at high concentrations in the lungs. The B.1.351 virus replicated to higher titers in the lungs compared to the B.1.1.7 and MA10 viruses. The levels of cytokines (IL-6, TNF-α, IL-1β) and chemokine (CCL2) were upregulated in response to the B.1.1.7 and B.1.351 infection in the lungs. Overall, these data indicate a greater potential for infectivity and adaptation to new hosts by emerging SARS-CoV-2 variants.

Download Full-text

Measles virus-induced modulation of host-cell gene expression

Journal of General Virology ◽

10.1099/0022-1317-83-5-1157 ◽

2002 ◽

Vol 83 (5) ◽

pp. 1157-1165 ◽

Cited By ~ 46

Author(s):

Gert Bolt ◽

Kurt Berg ◽

Merete Blixenkrone-Møller

Keyword(s):

Gene Expression ◽

Host Cell ◽

Measles Virus ◽

Mononuclear Cells ◽

Human Peripheral Blood ◽

B Cell Lymphoma ◽

Endoplasmic Reticulum Stress Response ◽

Wild Type Virus ◽

Mrna Levels ◽

Wild Type

The influence of measles virus (MV) infection on gene expression by human peripheral blood mononuclear cells (PBMCs) was examined with cDNA microarrays. The mRNA levels of more than 3000 cellular genes were compared between uninfected PBMCs and cells infected with either the Edmonston MV strain or a wild-type MV isolate. The MV-induced upregulation of individual genes identified by microarray analyses was confirmed by RT–PCR. In the present study, a total of 17 genes was found to be upregulated by MV infection. The Edmonston strain grew better in the PBMC cultures than the wild-type MV, and the Edmonston strain was a stronger inducer of the upregulated host cell genes than the wild-type virus. The anti-apoptotic B cell lymphoma 3 (Bcl-3) protein and the transcription factor NF-κB p52 subunit were upregulated in infected PBMCs both at the mRNA and at the protein level. Several genes of the interferon system including that for interferon regulatory factor 7 were upregulated by MV. The genes for a number of chaperones, transcription factors and other proteins of the endoplasmic reticulum stress response were also upregulated. These included the gene for the pro-apoptotic and growth arrest-inducing CHOP/GADD153 protein. Thus, the present study demonstrated the activation by MV of cellular mechanisms and pathways that may play a role in the pathogenesis of measles.

Download Full-text