mSphere

mSphere of Influence: Retreading old ground—the beauty in multi-omic data sets

ABSTRACT Ethan L. Morgan works on human papillomaviruses (HPVs), with a specific interest in identifying how HPV induces tumor formation. In this mSphere of Influence article, he reflects on how three papers influenced him. “Comprehensive genomic characterization of head and neck squamous cell carcinomas” (The Cancer Genome Atlas Network, Nature 517:576–582, 2015, https://doi.org/10.1038/nature14129 ) and “Integrated genomic and molecular characterization of cervical cancer” (The Cancer Genome Atlas Network, Nature 543: 378–384, 2017, https://doi.org/10.1038/nature21386 ) showed him the power behind comprehensive multi-omic analyses to understand disease biology, while “Human papillomavirus E7 oncoprotein targets RNF168 to hijack the host DNA damage response” (J. Sitz et al., Proc Natl Acad Sci U S A 116:19552–19562, 2019, https://doi.org/10.1073/pnas.1906102116 ) reinforced how this can be used to undercover potential new drug targets in HPV-associated disease.

Human Papillomavirus 16 E6 and E7 Synergistically Repress Innate Immune Gene Transcription

The role of human papillomavirus 16 (HPV16) in human cancers is well established; however, to date there are no antiviral therapeutics that are available for combatting these cancers. To identify such targets, we must enhance the understanding of the viral life cycle. Innate immune genes (IIGs) are repressed by HPV16, and we have reported that this repression persists through to cancer. Reversal of this repression would boost the immune response to HPV16-positive tumors, an area that is becoming more important given the advances in immunotherapy. This report demonstrates that E6 and E7 synergistically repress IIG expression in the context of the entire HPV16 genome. Removal of either protein activates the expression of IIGs by HPV16. Therefore, gaining a precise understanding of how the viral oncogenes repress IIG expression represents an opportunity to reverse this repression and boost the immune response to HPV16 infections for therapeutic gain.