What function do the E6 and E7 (Early proteins 6 and 7) genes play in papillomavirus replication?

Function of HPV E6 and E7 Genes in Viral Replication

The E6 and E7 genes of papillomavirus primarily function to promote entry of the host cell into the S phase of the cell cycle, allowing the virus to commandeer the host replication apparatus for viral DNA replication.

Mechanism of Action of E6 and E7 Proteins

HPV E6 and E7 are early proteins that play crucial roles in the viral life cycle by manipulating host cell regulatory machinery. Their functions include:

E6 Protein:

• Binds to and promotes degradation of p53 tumor suppressor protein 1
• Blocks apoptosis (programmed cell death)
• Manipulates cell cycle regulators 1

E7 Protein:

• Binds to and inactivates retinoblastoma (Rb) tumor suppressor protein 1
• Disrupts the Rb-E2F complex, releasing E2F transcription factors
• Induces chromosomal abnormalities 1

Cell Cycle Manipulation for Viral Replication

Papillomaviruses have a small genome and lack their own DNA replication machinery. To replicate, they must:

1. Force normally non-dividing differentiated epithelial cells to re-enter the cell cycle
2. Access the host cell's DNA replication machinery
3. Create an environment conducive to viral genome replication

The E6 and E7 proteins accomplish this by:

• Promoting cell cycle progression into S phase where cellular DNA synthesis occurs
• Preventing cell cycle arrest that would normally occur in response to viral infection
• Creating an environment where viral DNA can replicate using host cell machinery 1

Specific Cellular Targets

E6 and E7 interact with multiple cellular proteins to achieve their functions:

• E6 targets p53, preventing it from inducing cell cycle arrest or apoptosis in response to abnormal DNA replication signals 1
• E7 targets Rb, disrupting its normal function of preventing cells from entering S phase 1
• Together, they manipulate cell cycle regulators, allowing infected cells that would normally be non-dividing to remain in an active cell cycle 1

Consequences for Viral Life Cycle

This manipulation of the cell cycle has important consequences:

• Differentiating epithelial cells that would normally exit the cell cycle remain active
• The host cell's DNA replication machinery becomes available for viral genome amplification
• The virus can complete its life cycle in cells that would otherwise not support replication

Oncogenic Potential

In high-risk HPV types, persistent expression of E6 and E7 can lead to:

• Immortalization of cells
• Accumulation of genetic mutations
• Chromosomal abnormalities
• Eventual malignant transformation 1

The ability of E6 and E7 to promote entry into S phase is therefore not only essential for viral replication but also underlies the oncogenic potential of high-risk HPV types.

Based on the evidence presented, the correct answer is D. Promotes entry of the cell into the S phase of the cell cycle to allow the virus to commandeer the host replication apparatus.