Analysis of wild-type and C mutant human HPIV1 and interferon beta treatment in human respiratory epithelial A549 cells

ABSTRACT: HPIV1 is an important respiratory pathogen in children and the most common cause of viral croup. We performed a microarray-based analysis of gene expression kinetics to examine how wild-type (wt) HPIV1 infection altered gene expression in human respiratory epithelial cells and what role IFN-beta played in this response. We similarly evaluated HPIV1-P(C-), a highly attenuated and apoptosis-inducing virus that does not express any of the four C proteins, and HPIV1-C(F170S), a less attenuated mutant that contains a single point mutation in C and, like wt HPIV1, does not efficiently induce apoptosis, to examine the role of the C proteins in controlling host gene expression. We also used this data to investigate whether the phenotypic differences between the two C mutants could be explained at the transcriptional level. Mutation or deletion of the C proteins of HPIV1 permitted the activation of over 2000 cellular genes that otherwise would be repressed by HPIV1 infection. Thus, the C proteins profoundly suppress the response of human respiratory cells to HPIV1 infection. Cellular pathways targeted by the HPIV1 C proteins were identified and their transcriptional control was analyzed using bioinformatics. Transcription factor binding sites for IRF and NF-kappaB were over-represented in some of the C protein targeted pathways, but other pathways were dominated by less known factors such as forkhead transcription factor FOXD1. Surprisingly, the host response to the C knockout and C(F170S) mutants was very similar, and thus the phenotypic differences between these two viruses could not be explained at the host cell transcriptional level. Keywords: Time course; response to viral infection; response to IFN-beta

ORGANISM(S): Homo sapiens

PROVIDER: GSE12664 | GEO | 2008/12/22

SECONDARY ACCESSION(S): PRJNA112731

REPOSITORIES: GEO