HIV-associated disruption of mucosal epithelium facilitates paracellular penetration by human papillomavirus.
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.
Department of Medicine, University of California San Francisco, 513 Parnassus Ave, San Francisco, CA 94143-0512, USA; Department of Orofacial Sciences, University of California San Francisco, 513 Parnassus Ave, San Francisco, CA 94143-0512, USA. Electronic address: sharof.tugizov@ucsf.edu.
Sharof M
SM
Tugizov
Rossana
R
Herrera
Peter
P
Chin-Hong
Piri
P
Veluppillai
Deborah
D
Greenspan
J
J
Michael Berry
Christopher D
CD
Pilcher
Caroline H
CH
Shiboski
Naomi
N
Jay
Mary
M
Rubin
Aung
A
Chein
Joel M
JM
Palefsky
D002478:Cells, Cultured; D004848:Epithelium / Q000473:pathology* / Q000821:virology*; D015658:HIV Infections / Q000150:complications* / Q000473:pathology / Q000821:virology; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology* / Q000821:virology*; D009924:Organ Culture Techniques; D027383:Papillomaviridae / Q000472:pathogenicity*; D030361:Papillomavirus Infections / Q000473:pathology / Q000821:virology*; D019108:Tight Junctions / Q000502:physiology
Disruption of tight junctions; HIV; HPV; HPV paracellular penetration; Mucosal epithelium