Immune evasion mechanisms of human papillomavirus: An update

Abstract

Human papillomavirus (HPV) is the most frequently sexually transmitted agent in the world. It can cause cervical and other anogenital malignancies, and oropharyngeal cancer. HPV has the unique ability to persist in the host's epithelium for a long time-longer than most viruses do-which is necessary to complete its replication cycle. To this end, HPV has developed a variety of immune evasion mechanisms, which unfortunately also favor the progression of the disease from infection to chronic dysplasia and eventually to cancer. This article summarizes the current knowledge about HPV immune evasion strategies. A special emphasis lies in HPV-mediated changes of the antigen processing machinery, which is generating epitopes for T cells and contributes to the detectability of infected cells.

A Targeted LC‐MS Strategy for Low‐Abundant HLA Class‐I‐Presented Peptide Detection Identifies Novel Human Papillomavirus T‐Cell Epitopes

“…However, only one HLA‐A2‐restricted HPV16 peptide, E7 11–19 , was directly detected on the surface of HPV16 + cell lines13 and primary tumors 14. This is probably due to the fact that the amounts of HPV epitopes presented on the cell surface are extremely low, because of low viral protein expression and known HPV immune evasion mechanisms 15, 16…”

Is there a role played by HLA‐E, if any, in HPV immune evasion?

“…In addition, HLA‐A and HLA‐B molecules can be retained intracellularly by various mechanisms mediated by the viral protein E5. Interestingly, HLA‐C and HLA‐E are not influenced by the E5 protein …”

“…Viral avoidance strategies that interfere with peptide transportation pathways prevent proper detection of T‐lymphocyte‐infected cells. Furthermore, as HPV does not cross the basement membrane, it becomes less exposed to the action of immune cells, which contribute to the progression of the infection and the establishment of cervical neoplasms and/or cervical cancer …”

WHIM syndrome: Immunopathogenesis, treatment and cure strategies

“…There are over 200 known types of HPV which are defined by genetic differences of >10% in the major viral envelope gene L1, and immunity is often type‐specific . HPV has coevolved with humans and is species‐specific with multiple mechanisms of immune evasion making it difficult for the immune system to quickly eliminate the infection even in those with fully functional immune systems . Thus, it is not surprising that HPV infection is particularly severe in individuals who have acquired or congenital immunodeficiency and who may lack the means to efficiently recognize and eradicate the virus .…”

“…27 HPV has coevolved with humans and is species-specific with multiple mechanisms of immune evasion making it difficult for the immune system to quickly eliminate the infection even in those with fully functional immune systems. 28 Thus, it is not surprising that HPV infection is particularly severe in individuals who have acquired or congenital immunodeficiency and who may lack the means to efficiently recognize and eradicate the virus. 29 Nevertheless, the association of HPV as the signature pathogen in WHIM syndrome is unusually strong for a primary immunodeficiency disease.…”