A Mathematical Model of Cell Cycle Dysregulation Due to Human Papillomavirus Infection

作者：Miller Anna K^*; Munger Karl; Adler Frederick R

来源：Bulletin of Mathematical Biology, 2017, 79(7): 1564-1585.

DOI：10.1007/s11538-017-0299-9

• Mathematical model
• Retinoblastoma protein
• Human papillomaviruses
• HPV E7

Human papillomaviruses (HPVs) that infect mucosal epithelium can be classified as high risk or low risk based on their propensity to cause lesions that can undergo malignant progression. HPVs produce the E7 protein that binds to cell cycle regulatory proteins including the retinoblastoma tumor suppressor protein (RB) to modulate cell cycle control. Generally, high-risk HPV E7 proteins bind to RB with a higher affinity than low-risk HPV E7s, but both are able to deactivate RB and trigger S phase progression. In uninfected cells, RB inactivation is a tightly controlled process that must coincide with growth factor stimulation to commit cells to division. High-risk HPV E7 proteins short-circuit this control by decreasing growth factor requirement for cell division. We develop a mathematical model to examine the role that RB binding affinity, growth factor concentration, and E7 concentration have on cell cycle progression. Our model predicts that high RB binding affinity and E7 concentration accelerate the to S phase transition and weaken the dependence on growth factor. This model thus captures a key step in high-risk HPV oncogenesis.

• 出版日期2017-7