Infections with human papillomaviruses (HPVs) are the most common sexually transmitted infection in the US. In addition to causing cervical and other anogenital cancers and a rising incidence of head and neck cancer, HPVs are responsible for an estimated 5% of cancers worldwide. Importantly, persistent infection, and not an acute infection, is the primary risk factor for (cervical) cancer development. Thus, understanding the virus-host interplay that promotes or restricts viral persistence has important implications for HPV biology and human cancers. Until recently, it has been challenging to study the immediate early events of the HPV lifecycle following infection and how these events contribute to initial genome amplification during the establishment phase and long-term viral persistence. We used a single-cell genomics approach to identify cellular factors involved in viral infection and persistence. The R01, this diversity supplement proposal is associated with, explores how protein arginine N- methyltransferase 1 (PRMT1) regulates RBM15 controlled m6a deposition on viral mRNA to regulate alternative splicing throughout viral infection temporally. Amy Banka recently joined my lab to reanalyze large published genomics datasets using gene coexpression networks. Specifically, by comparing transcriptomes of HPV(+) cells along the progression from early infection to cancer progression, we aim to identify coexpression networks that will illuminate how HPV rewires these cells throughout the viral life cycle. This approach may identify new druggable targets or identify biomarkers to inform clinical practice.