When HPV infects host cells, several HPV DNA-coded proteins initiate cellular changes. Two such areas in the genome are the open reading frames E1 to E7 and the late open reading frames L1 and L2. An open reading frame is a portion of a DNA molecule that contains no stop codons when translated into amino acids.
The proteins encoded by the E1 to E7 genome regions are responsible for HPV gene regulation and cell transformation. Proteins resulting from L1 and L2 form the viral shell.
The E6 and E7 encoded proteins are the most important HPV proteins in malignancy transformations. These viral proteins work together to convert normal host cells into malignant cells. E6 proteins interact with the intracellular protein p53, and E7 proteins interact with the intracellular retinoblastoma (Rb) protein. The intracellular proteins p53 and Rb regulate cellular growth. Both p53 and Rb are tumor suppressor proteins.
When chromosomal damage occurs during normal cellular growth, p53 halts growth and allows DNA repair enzymes to repair the damage. Rb also halts growth in DNA damage by inducing apoptosis (cellular death). When HPV E6 proteins bind to p53 and HPV E7 to Rb, mutations accumulate, unchecked cellular growth occurs, and chromosomal instability results. This instability and unregulated cellular growth increase the chance of forming malignant cells.
Viral E1, E2, and E5 encoded proteins may also damage cellular processes when HPV infects cells and can lead to malignant transformations.
