Elsevier

Virology

Volume 446, Issues 1–2, November 2013, Pages 378-388
Virology

HIV-associated disruption of mucosal epithelium facilitates paracellular penetration by human papillomavirus

https://doi.org/10.1016/j.virol.2013.08.018Get rights and content
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Highlights

  • HIV proteins tat and gp120 were expressed within the oral and anal mucosal epithelial microenvironment of HIV-infected individuals.

  • Expression of HIV proteins in the mucosal epithelium was correlated with the disruption of epithelial tight junctions.

  • Treatment of oral epithelial cells and tissue explants with tat and gp120 led to disruption of epithelial tight junctions.

  • HIV tat/gp120-induced disruption of tight junctions increased HPV pseudovirion paracellular penetration into the epithelium.

  • HIV-associated tight junctions disruption of mucosal epithelia may potentiate HPV infection and subsequent development of HPV-associated neoplasia.

Abstract

The incidence of human papillomavirus (HPV)-associated epithelial lesions is substantially higher in human immunodeficiency virus (HIV)-infected individuals than in HIV-uninfected individuals. The molecular mechanisms underlying the increased risk of HPV infection in HIV-infected individuals are poorly understood. We found that HIV proteins tat and gp120 were expressed within the oral and anal mucosal epithelial microenvironment of HIV-infected individuals. Expression of HIV proteins in the mucosal epithelium was correlated with the disruption of epithelial tight junctions (TJ). Treatment of polarized oral, cervical and anal epithelial cells, and oral tissue explants with tat and gp120 led to disruption of epithelial TJ and increased HPV pseudovirion (PsV) paracellular penetration in to the epithelium. PsV entry was observed in the basal/parabasal cells, the cells in which the HPV life cycle is initiated. Our data suggest that HIV-associated TJ disruption of mucosal epithelia may potentiate HPV infection and subsequent development of HPV-associated neoplasia.

Keywords

HIV
HPV
Mucosal epithelium
Disruption of tight junctions
HPV paracellular penetration

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