Papillomaviruses

Stanley, Margaret; Pett, Mark R.

doi:10.1002/9780470688618.taw0229

Cited by 1 publication

(1 citation statement)

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“…Viral gene expression is confined to the keratinocyte; there is no evidence that viral genes are expressed in any cell other than keratinocytes, and importantly, there is a differential spatial and temporal pattern of HPV gene expression in the infected epithelium ( Fig. 1 and 2) (72). After infection of wound basal cells, it is thought that there is a round of viral DNA replication that appears to be independent of the cell cycle and amplifies the viral copy number to around 50 to 100 copies per cell.…”

Section: Hpv Infectious Cyclementioning

confidence: 99%

Epithelial Cell Responses to Infection with Human Papillomavirus

2012

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SUMMARY Human papillomavirus (HPV) infection of the genital tract is common in young sexually active individuals, the majority of whom clear the infection without overt clinical disease. Most of those who do develop benign lesions eventually mount an effective cell-mediated immune (CMI) response, and the lesions regress. Regression of anogenital warts is accompanied histologically by a CD4 + T cell-dominated Th1 response; animal models support this and provide evidence that the response is modulated by antigen-specific CD4 + T cell-dependent mechanisms. Failure to develop an effective CMI response to clear or control infection results in persistent infection and, in the case of the oncogenic HPVs, an increased probability of progression to high-grade intraepithelial neoplasia and invasive carcinoma. Effective evasion of innate immune recognition seems to be the hallmark of HPV infections. The viral infectious cycle is exclusively intraepithelial: there is no viremia and no virus-induced cytolysis or cell death, and viral replication and release are not associated with inflammation. HPV globally downregulates the innate immune signaling pathways in the infected keratinocyte. Proinflammatory cytokines, particularly the type I interferons, are not released, and the signals for Langerhans cell (LC) activation and migration, together with recruitment of stromal dendritic cells and macrophages, are either not present or inadequate. This immune ignorance results in chronic infections that persist over weeks and months. Progression to high-grade intraepithelial neoplasia with concomitant upregulation of the E6 and E7 oncoproteins is associated with further deregulation of immunologically relevant molecules, particularly chemotactic chemokines and their receptors, on keratinocytes and endothelial cells of the underlying microvasculature, limiting or preventing the ingress of cytotoxic effectors into the lesions. Recent evidence suggests that HPV infection of basal keratinocytes requires epithelial wounding followed by the reepithelization of wound healing. The wound exudate that results provides a mechanistic explanation for the protection offered by serum neutralizing antibody generated by HPV L1 virus-like particle (VLP) vaccines.

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Section: Hpv Infectious Cyclementioning

confidence: 99%