Measles virus-induced modulation of host-cell gene expression.
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-kappaB 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.
Bolt
Gert
G
Laboratory of Virology and Immunology, Royal Veterinary and Agricultural University, Bülowsvej 17, 1870 Frederiksberg C, Denmark1.
Berg
Kurt
K
Department of Medical Microbiology and Immunology, Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark2.
Blixenkrone-Møller
Merete
M
Laboratory of Virology and Immunology, Royal Veterinary and Agricultural University, Bülowsvej 17, 1870 Frederiksberg C, Denmark1.
D000081242:B-Cell Lymphoma 3 Protein; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000821:virology; D008459:Measles virus / Q000502:physiology*; D016328:NF-kappa B / Q000235:genetics; D052002:NF-kappa B p50 Subunit; D020411:Oligonucleotide Array Sequence Analysis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D015854:Up-Regulation
D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D016898:Interferon-alpha; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors