Host cell transcriptome modification upon exogenous HPV16 L2 protein expression

Human papillomavirus type 16 minor capsid protein L2 has been shown to assist in the initial entry and intracellular trafficking events leading to nuclear translocation of the viral genome. During our investigations of L2 function, we observed that expression of L2 in a keratinocyte cell line (HaCaT) resulted in phenotypic changes. In this manuscript, we present data that expression of the L2 protein in this cellular model system HaCaTs resulted in a shift from G0/G1 phase to mitotic S phase, as well as a reduced amount of retinoblastoma protein (Rb) and an increase in Cdc2 phosphorylation. We performed genome-wide host cell mRNA sequencing and identified 2586 differentially expressed genes upon HPV16 L2 expression. Via machine learning and protein network analysis, genes involved in cellular differentiation and proliferation were highlighted as impacted by L2. Our results have implications for the role of L2 at the viral production stages when the virus needs to prevent cellular differentiation while maintaining the cells ability to replicate DNA. Our study suggests a potential novel function of the L2 protein, as a regulator of cellular gene transcription.