Virus–Host Protein–Protein Interactions between Human Papillomavirus 16 E6 A1 and D2/D3 Sub-Lineages: Variances and Similarities

Round 1

Reviewer 1 Report

This is an interesting manuscript that provides mechanistic explanation on the oncogenicity of different human papillomavirus (HPV) E6 variants. The work is solid and of interest for the HPV community. Although, the manuscript is descriptive, it will facilitate additional studies focused on elucidating the HPV-mediated mechanisms in cellular transformation.

Reviewer 2 Report

Human papillomavirus type 16 is responsible for most cancers associated with HPV infection. Population studies by authors and others demonstrated that the common Asian–American E6 variant is a higher risk factor for cervical cancer than the European prototype. However, a complete understanding of the molecular processes fundamental to these epidemiological findings is still lacking. The studies showed that AAE6 had a higher immortalization and transformation potential than European prototype. Here the study identified using liquid chromatography-mass spectrometry and stringent interactor selection criteria several unique cellular interacting proteins. The study showed the intratypic HPV 16 variants differ Notch signaling, energetics and hypoxia, DNA replication and repair, and immune response. The future in HPV field is not only identified the high-risk HPV types but also the variants of these type. The study like this is necessary for understanding of the molecular processes of HPV 16 variants.