Gene expression patterns in dendritic cells infected with measles virus compared with other pathogens

Abstract

Gene expression patterns supply insight into complex biological networks that provide the organization in which viruses and host cells interact. Measles virus (MV) is an important human pathogen that induces transient immunosuppression followed by life-long immunity in infected individuals. Dendritic cells (DCs) are potent antigen-presenting cells that initiate the immune response to pathogens and are postulated to play a role in MV-induced immunosuppression. To better understand the interaction of MV with DCs, we examined the gene expression changes that occur over the first 24 h after infection and compared these changes to those induced by other viral, bacterial, and fungal pathogens. There were 1,553 significantly regulated genes with nearly 60% of them down-regulated. MV-infected DCs up-regulated a core of genes associated with maturation of antigen-presenting function and migration to lymph nodes but also included genes for IFN-regulatory factors 1 and 7, 2 5 oligoadenylate synthetase, Mx, and TNF superfamily proteins 2, 7, 9, and 10 (TNF-related apoptosisinducing ligand). MV induced genes for IFNs, ILs, chemokines, antiviral proteins, histones, and metallothioneins, many of which were also induced by influenza virus, whereas genes for protein synthesis and oxidative phosphorylation were down-regulated. Unique to MV were the induction of genes for a broad array of IFN-␣s and the failure to up-regulate dsRNA-dependent protein kinase. These results provide a modular view of common and unique DC responses after infection and suggest mechanisms by which MV may modulate the immune response.immunosuppression ͉ IFN ͉ microarray ͉ dsRNA-dependent protein kinase

Unravelling the interaction of human cytomegalovirus with dendritic cells by using SuperSAGE

“…The genes induced most strongly by HCMV infection included three chemokines (CCL5, CCL8, CXCL10) and the ISGs MX1 and G1P2 (Table 2). Upregulation of CCL4, CCL5 and CXCL10 is characteristic of DC maturation (Hashimoto et al, 2000;Sallusto et al, 1999) and is also seen after measles virus infection of DCs (Zilliox et al, 2006). We confirmed the upregulation of CCL4, CCL5 and CXCL10 from 0 to 12 h by using qRT-PCR (Fig.…”

“…This downregulation may be potentiated further by transcripts such as IFIT1, which is known to inhibit eIF3e (Hui et al, 2003). In addition, the downregulation of the mitochondrial ATPase (MT-ATP6) and the mitochondrial cytochrome c oxidase subunit II (MT-CO2) ( Table 3) parallels downregulation of genes in the oxidative phosphorylation pathway seen during measles virus infection (Zilliox et al, 2006). Finally, our results indicate an unexpected divergence in genes controlled by the class II transactivator (CIITA).…”

“…We further compared our data with RNA virus infection of DCs (Huang et al, 2001;Zilliox et al, 2006). The cellular genes QKI, G1P3, HLA-DPB1, ECGF and GRIM19 are altered by HCMV infection in DCs, but have not been reported previously to be affected either by HCMV infection or in RNA virus-infected DCs.…”

“…The genes expressed within DCs, both viral and cellular, are of particular interest to understand how viruses evade the immune response and replicate in these rare cells. Recent research has revealed the changes in cellular transcripts taking place in DCs upon infection with RNA viruses (Huang et al, 2001;Izmailova et al, 2003;Zilliox et al, 2006), but no data are available for herpesviruses. The betaherpesvirus human cytomegalovirus (HCMV) is a clinically relevant DNA virus that causes significant pathology in immunosuppressed patients and newborn infants.…”

Measles virus modulates chemokine release and chemotactic responses of dendritic cells

“…Additionally, CCL-20 was not induced by higher virus doses (not shown). In contrast, CCL-20 transcripts were found to accumulate in MV-infected DCs in a microarray-based study (Zilliox et al, 2006). Given the reproducibility of our assay systems for LPS-DC SNs, technical issues are unlikely to account for this discrepancy.…”