Host response to the attenuated poxvirus vector NYVAC: upregulation of apoptotic genes and NF-kappaB-responsive genes in infected HeLa cells.

Abstract:

:NYVAC has been engineered as a safe, attenuated vaccinia virus (VV) vector for use in vaccination against a broad spectrum of pathogens and tumors. Due to the interest in NYVAC-based vectors as vaccines and current phase I/II clinical trials with this vector, there is a need to analyze the human host response to NYVAC infection. Using high-density cDNA microarrays, we found 368 differentially regulated genes after NYVAC infection of HeLa cells. Clustering of the regulated genes identified six discrete gene clusters with altered expression patterns. Clusters 1 to 3 represented 47.5% of the regulated genes, with three patterns of gene activation kinetics, whereas clusters 4 to 6 showed distinct repression kinetics. Quantitative real-time reverse transcription-PCR analysis of selected genes validated the array data. Upregulated transcripts correlated with genes implicated in immune responses, including those encoding interleukin-1 receptor 2 (IL-1R2), IL-6, ISG-15, CD-80, and TNFSF7. NYVAC upregulated several intermediates of apoptotic cascades, including caspase-9, correlating with its ability to induce apoptosis. NYVAC infection also stimulated the expression of NF-kappaB1 and NF-kappaB2 as well as that of NF-kappaB target genes. Expression of the VV host range K1L gene during NYVAC infection prevented NF-kappaB activation, but not the induction of apoptosis. This study is the first overall analysis of the transcriptional response of human cells to NYVAC infection and provides a framework for future functional studies to evaluate this vector and its derivatives as human vaccines.

journal_name

J Virol

journal_title

Journal of virology

authors

Guerra S,López-Fernández LA,Pascual-Montano A,Nájera JL,Zaballos A,Esteban M

doi

10.1128/JVI.80.2.985-998.2006

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

985-98

issue

2

eissn

0022-538X

issn

1098-5514

pii

80/2/985

journal_volume

80

pub_type

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