IPVC 2021 Basic Sciences Virtual Poster Walk with Dr. Alix Warburton

Laboratory of Viral Diseases, National Institute of Allergy And Infectious Diseases, National Institutes Of Health, Bethesda, Maryland, USA

Specialty: Viral persistence and integration

The quality of the E-Posters presented at IPVC 2021 was outstanding. Several posters described high-throughput screens that advance our understanding of HPV gene regulation and viral persistence. Poster 252, entitled IDENTIFICATION OF HUMAN TRANSCRIPTION FACTORS THAT REGULATE THE LCR OF DIFFERENT VARIANTS OF HPV-18 AND -16, identified novel transcription factors that were shown to regulate the transcriptional activity of HPV16 and HPV18 variants through a reporter-based assay. Several transcription factors were identified as putative regulators of the LCR through in silico analyses, which could open therapeutic avenues for the treatment of persistent HPV infections.

In Poster 115, HIGH THROUGHPUT SCREENING IDENTIFIES SMALL MOLECULE INHIBITORS AGAINST PERSISTENT HPV16 INFECTIONS, Zheng et al. performed a high-throughput screen of small molecule inhibitors against persistent HPV infection and identified drug L as an antagonist of HPV16 E6 protein function in keratinocytes that was shown to act through a p53-independent mechanism.

Poster 508, HPV18-RELATED CARCINOGENESIS PROVIDES CANCER STEM CELL FEATURES: CHARACTERIZATION OF THE IPS CELL-DERIVED RESERVE-LIKE CELL (IRC) WITH INTEGRATION OF HPV16 OR 18 ONCOGENES, also caught my attention as an innovative way of dissecting the distinct regulatory pathways of HPV16 and HPV18 infected cells. In this study, Kamata et al. generated reserve-like cells from induced pluripotent stem cells and performed global gene expression profiling following HPV16 and HPV18 E6/E7 transduction. The findings of this study will inform our understanding of the distinct carcinogenic potential of these high-risk viral types in HPV-associated cancers.

Another poster of interest, entitled THE HIGH-RISK HPV16 E7 CARBOXYL-TERMINUS BINDS TO ZER1 IN HUMAN KERATINOCYTES (Poster 200), identified the specific residues within the C-terminal domain of the HPV16 E7 protein that are required for its interaction with ZER1 and Cullin 2, an E3 ubiquitin ligase complex that is required for HPV16 E7-induced degradation of RB1. Cellular growth was shown to be impaired in HPV16-positve ZER1 knockout cells, and cells expressing the C-terminal domain mutants reduced the immortalization capacity of the HPV16 E7 protein. These data build on our knowledge of the carcinogenic activity of HPV16-E7 and provide potential druggable targets for therapeutic intervention in HPV-positive tumors.

Please check out the fantastic work presented at this year’s IPVC E-poster gallery and swing by Poster 355, THE PAPILLOMAVIRUS EPISTEME – AN UPDATE, to explore the new features of PaVE 2.0 (https://pave.niaid.nih.gov/) that will be launched soon.