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Journal of Virology, August 2007, p. 8707-8721, Vol. 81, No. 16
0022-538X/07/$08.00+0     doi:10.1128/JVI.00444-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Distinct Gene Expression Profiling after Infection of Immature Human Monocyte-Derived Dendritic Cells by the Attenuated Poxvirus Vectors MVA and NYVAC{triangledown} ,{dagger}

Susana Guerra,1 José Luis Nájera,1 José Manuel González,1 Luis A. López-Fernández,2 Nuria Climent,3,5 José M. Gatell,3,5 Teresa Gallart,4,5 and Mariano Esteban1*

Department of Molecular and Cellular Biology,1 Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Campus Universidad Autónoma, E-28049 Madrid, Spain,2 Servicios de Enfermedades Infecciosas,3 de Inmunología, Hospital Clínic de Barcelona,4 AIDS Research Group, Instituto de Investigaciones Biomedicas August Pi i Sunyer (IDIBAPS), Universidad de Barcelona, Villaroel 170, 08036 Barcelona, Spain5

Received 1 March 2007/ Accepted 17 May 2007

Although recombinants based on the attenuated poxvirus vectors MVA and NYVAC are currently in clinical trials, the nature of the genes triggered by these vectors in antigen-presenting cells is poorly characterized. Using microarray technology and various analysis conditions, we compared specific changes in gene expression profiling following MVA and NYVAC infection of immature human monocyte-derived dendritic cells (MDDC). Microarray analysis was performed at 6 h postinfection, since these viruses induced extensive cytopathic effects, rRNA breakdown, and apoptosis at late times postinfection. MVA- and NYVAC-infected MDDC shared upregulation of 195 genes compared to uninfected cells: MVA specifically upregulated 359 genes, and NYVAC upregulated 165 genes. Microarray comparison of NYVAC and MVA infection revealed 544 genes with distinct expression patterns after poxvirus infection and 283 genes specifically upregulated after MVA infection. Both vectors upregulated genes for cytokines, cytokine receptors, chemokines, chemokine receptors, and molecules involved in antigen uptake and processing, including major histocompatibility complex genes. mRNA levels for interleukin 12ß (IL-12ß), beta interferon, and tumor necrosis factor alpha were higher after MVA infection than after NYVAC infection. The expression profiles of transcription factors such as NF-{kappa}B/Rel and STAT were regulated similarly by both viruses; in contrast, OASL, MDA5, and IRIG-I expression increased only during MVA infection. Type I interferon, IL-6, and Toll-like receptor pathways were specifically induced after MVA infection. Following MVA or NYVAC infection in MDDC, we found similarities as well as differences between these virus strains in the expression of cellular genes with immunological function, which should have an impact when these vectors are used as recombinant vaccines.

* Corresponding author. Mailing address: Centro Nacional de Biotecnología, CSIC, Campus Universidad Autónoma, 28049 Madrid, Spain. Phone: (34) 91/585-4553. Fax: (34) 91/585-4506. E-mail: mesteban{at}cnb.uam.es

{triangledown} Published ahead of print on 30 May 2007.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, August 2007, p. 8707-8721, Vol. 81, No. 16
0022-538X/07/$08.00+0     doi:10.1128/JVI.00444-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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