HPV-host interactions
HPV enters the host cells through microtraumas or breaches in the epithelial barrier. The virus attaches to the host cell surface receptors, which can include heparan sulfate proteoglycans and specific cellular receptors such as alpha-6 integrin. These interactions facilitate the internalization of the virus into the host cell.12,19,20,22,40-42
HPV has evolved strategies to evade the host immune response. The virus can inhibit interferon signaling, interfere with antigen presentation, and modulate immune cell functions. By evading immune detection and clearance, HPV can establish persistent infections and increase the risk of disease progression.12,19,22,42
Once inside the host cell, HPV relies on the host cell machinery for gene expression. The viral genome is replicated and transcribed using host cell enzymes. The expression of viral genes is tightly regulated to ensure that specific viral proteins are produced at different stages of the infection cycle.9,19,20,40-44
High-risk HPV types, such as HPV16 and HPV18, can cause cellular transformation, leading to the development of cancer. The viral oncoproteins E6 and E7 play a critical role in this process. E6 proteins can bind and degrade p53, a tumor suppressor protein that regulates cell cycle arrest and DNA repair. E7 proteins bind and inactivate retinoblastoma (Rb) protein, which regulates cell cycle progression. Dysregulation of these key cellular processes by viral oncoproteins can lead to uncontrolled cell proliferation and the formation of tumors.9,12,20,22,40-44
HPV replicates its DNA in synchrony with the host cell’s DNA replication machinery. The viral genome utilizes host cell factors and enzymes to replicate its DNA during S phase of the cell cycle. The virus has mechanisms to ensure proper timing and coordination between viral and host DNA replication.7,9,12,21,39
HPV infections are typically associated with the differentiation of epithelial cells. As infected cells move toward the upper layers of the epithelium and differentiate, viral gene expression changes. Late viral genes, which encode structural proteins, are expressed, leading to the production of new viral particles.2,9,20-22,41-43
The host immune response plays a critical role in controlling HPV infection. Both innate and adaptive immune responses are involved in recognizing and eliminating HPV-infected cells. Immune cells, such as cytotoxic T lymphocytes (CTLs), natural killer (NK) cells, and antigen-presenting cells (APCs), are involved in recognizing and clearing infected cells.9,12,22,29,42,44