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