Mechanisms of persistence by small DNA tumor viruses

Abstract

Virus infection contributes to nearly 15% of human cancers worldwide. Many of the oncogenic viruses tend to cause cancer in immunosuppressed individuals, but maintain asymptomatic, persistent infection for decades in the general population. In this review, we discuss the tactics employed by two small DNA tumor viruses, Human papillomavirus (HPV) and Merkel cell polyomavirus (MCPyV), to establish persistent infection. We will also highlight recent key findings as well as outstanding questions regarding the mechanisms by which HPV and MCPyV evade host immune control to promote their survival. Since persistent infection enables virus-induced tumorigenesis, identifying the mechanisms by which small DNA tumor viruses achieve latent infection may inform new approaches for preventing and treating their respective human cancers.

Figure 1.

The HPV infectious cycle. HPV virions (green circles) access basal epithelial cells through microabrasions in the epidermis. HPV genomes replicate at a low level in these cells and are maintained as episomes tethered to host chromatin. Late gene expression and virion production are completed upon keratinocyte differentiation and migration to the outer layers of the epidermis where immune surveillance is reduced. (Not drawn to scale).

Figure 2.

The proposed MCPyV infectious cycle. MCPyV infects human dermal fibroblasts, and not other skin cell types, in ex vivo culture. MCPyV infectious particles (yellow circles) may reach the dermal layer through deep abrasions. Fibroblasts closest to the basement membrane and hair follicles support the greatest MCPyV infection in ex vivo culture. Cells within the hair follicle may support MCPyV infection or may be a critical route of transmission. (Not drawn to scale).