Abstract
Persistent infections with a high-risk type human papillomavirus (hrHPV) can progress to cancer. High-risk HPVs infect keratinocytes (KCs) and successfully suppress host immunity for up to two years despite the fact that KCs are well equipped to detect and initiate immune responses to invading pathogens. Viral persistence is achieved by active interference with KCs innate and adaptive immune mechanisms. To this end hrHPV utilizes proteins encoded by its viral genome, as well as exploits cellular proteins to interfere with signaling of innate and adaptive immune pathways. This results in impairment of interferon and pro-inflammatory cytokine production and subsequent immune cell attraction, as well as resistance to incoming signals from the immune system. Furthermore, hrHPV avoids the killing of infected cells by interfering with antigen presentation to antigen-specific cytotoxic T lymphocytes. Thus, hrHPV has evolved multiple mechanisms to avoid detection and clearance by both the innate and adaptive immune system, the molecular mechanisms of which will be dealt with in detail in this review.
Highlights
Human papillomaviruses (HPVs) are small, non-enveloped icosahedral viruses belonging to the Papillomaviridae family
Keratinocytes are well equipped to recognize and react to invading pathogens, and high-risk type human papillomavirus (hrHPV) is no exception to immune evasion mechanisms soon after infecting the to this
Of the thirty-two candidate genes involved in these pathways, including TLR3, NFκB1, NFκB2, RelA, RelB, TRAF3 and TRAF6, only a single nucleotide polymorphisms (SNPs) in the 5’ UTR of the lymphotoxin alpha (LTA; TNF superfamily member 1) was significantly associated with increased risks of cervical and vulvar cancers [103]
Summary
Human papillomaviruses (HPVs) are small, non-enveloped icosahedral viruses belonging to the Papillomaviridae family. High-risk HPV (hrHPV) types are responsible for 5% of all human cancers and are detected in 99.7% of cervical cancer cases, the fourth most common cancer in women, accounting for 7.5% of all cancer-associated deaths in women worldwide per year [6,7]. High-risk HPV infections can persist despite viral activity in keratinocytes This indicates that HPV has developed mechanisms to effectively evade or suppress the host’s innate and/or adaptive immune response. After the infection is established in basal keratinocytes, major viral gene expression is differentiation dependent and as such viral peptide presentation to immune cells is limited. Besides these passive mechanisms to evade the immune system, hrHPV actively interferes with innate and adaptive immune mechanisms.
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