A systems biology approach to identify the combination effects of human herpesvirus 8 genes on NF-kappaB activation.

Journal of Virology
Andreas KonradMichael Stürzl

Abstract

Human herpesvirus 8 (HHV-8) is the etiologic agent of Kaposi's sarcoma and primary effusion lymphoma. Activation of the cellular transcription factor nuclear factor-kappa B (NF-kappaB) is essential for latent persistence of HHV-8, survival of HHV-8-infected cells, and disease progression. We used reverse-transfected cell microarrays (RTCM) as an unbiased systems biology approach to systematically analyze the effects of HHV-8 genes on the NF-kappaB signaling pathway. All HHV-8 genes individually (n = 86) and, additionally, all K and latent genes in pairwise combinations (n = 231) were investigated. Statistical analyses of more than 14,000 transfections identified ORF75 as a novel and confirmed K13 as a known HHV-8 activator of NF-kappaB. K13 and ORF75 showed cooperative NF-kappaB activation. Small interfering RNA-mediated knockdown of ORF75 expression demonstrated that this gene contributes significantly to NF-kappaB activation in HHV-8-infected cells. Furthermore, our approach confirmed K10.5 as an NF-kappaB inhibitor and newly identified K1 as an inhibitor of both K13- and ORF75-mediated NF-kappaB activation. All results obtained with RTCM were confirmed with classical transfection experiments. Our work describes the first suc...Continue Reading

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Citations

Apr 7, 2010·The Journal of Clinical Investigation·Don Ganem
Jan 17, 2015·Viruses·Pravinkumar PurushothamanSubhash C Verma
Jul 21, 2015·Reviews in Medical Virology·Annie Cristhine Moraes Sousa-SquiavinatoDeilson Elgui De Oliveira
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Aug 5, 2017·Pathogens·Jennifer L DeCotiis, David M Lukac
Oct 6, 2019·Medical Microbiology and Immunology·Juliana Prado GonçalesMaria Rosangela Cunha Duarte Coêlho
Jan 31, 2020·PloS One·Barbara RuderChristoph Becker
Feb 23, 2012·Lab on a Chip·Elisabeth KuhnMichael Stürzl
Nov 4, 2015·Aging·Vinay MurtadakMichael Stürzl
May 6, 2017·Frontiers in Microbiology·Kawalpreet K Aneja, Yan Yuan
Aug 10, 2017·Pathogens·Jennifer L DeCotiis, David M Lukac

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