Human papillomavirus deregulates the response of a cellular network comprising of chemotactic and proinflammatory genes

Rezaul Karim, Craig Meyers, Claude Backendorf, Kristina Ludigs, Rienk Offringa, Gert Jan B. van Ommen, Cornelis J.M. Melief, Sjoerd H. van der Burg, Judith M. Boer

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94 Scopus citations

Abstract

Despite the presence of intracellular pathogen recognition receptors that allow infected cells to attract the immune system, undifferentiated keratinocytes (KCs) are the main targets for latent infection with high-risk human papilloma viruses (hrHPVs). HPV infections are transient but on average last for more than one year suggesting that HPV has developed means to evade host immunity. To understand how HPV persists, we studied the innate immune response of undifferentiated human KCs harboring episomal copies of HPV16 and 18 by genome-wide expression profiling. Our data showed that the expression of the different virus-sensing receptors was not affected by the presence of HPV. Poly(I:C) stimulation of the viral RNA receptors TLR3, PKR, MDA5 and RIG-I, the latter of which indirectly senses viral DNA through non-self RNA polymerase III transcripts, showed dampening in downstream signalling of these receptors by HPVs. Many of the genes downregulated in HPV-positive KCs involved components of the antigen presenting pathway, the inflammasome, the production of antivirals, pro-inflammatory and chemotactic cytokines, and components downstream of activated pathogen receptors. Notably, gene and/or protein interaction analysis revealed the downregulation of a network of genes that was strongly interconnected by IL-1β, a crucial cytokine to activate adaptive immunity. In summary, our comprehensive expression profiling approach revealed that HPV16 and 18 coordinate a broad deregulation of the keratinocyte's inflammatory response, and contributes to the understanding of virus persistence.

Original languageEnglish (US)
Article numbere17848
JournalPLoS One
Volume6
Issue number3
DOIs
StatePublished - Mar 21 2011

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Karim, R., Meyers, C., Backendorf, C., Ludigs, K., Offringa, R., van Ommen, G. J. B., Melief, C. J. M., van der Burg, S. H., & Boer, J. M. (2011). Human papillomavirus deregulates the response of a cellular network comprising of chemotactic and proinflammatory genes. PLoS One, 6(3), [e17848]. https://doi.org/10.1371/journal.pone.0017848