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.
Virology. 2013 Nov;446(1-2):378-88. doi: 10.1016/j.virol.2013.08.018. Epub 2013 Sep 17.
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.
人乳头瘤病毒（HPV）相关上皮病变在人类免疫缺陷病毒（HIV）感染个体中的发病率明显高于 HIV 未感染个体。HIV 感染个体中 HPV 感染风险增加的分子机制尚不清楚。我们发现，HIV 蛋白 tat 和 gp120 在 HIV 感染个体的口腔和肛门黏膜上皮微环境中表达。黏膜上皮中 HIV 蛋白的表达与上皮紧密连接（TJ）的破坏有关。用 tat 和 gp120 处理极化的口腔、宫颈和肛门上皮细胞和口腔组织外植体导致上皮 TJ 破坏，并增加 HPV 假病毒（PsV）旁细胞渗透进入上皮细胞。在基底/副基底细胞中观察到 PsV 进入，这是 HPV 生命周期开始的细胞。我们的数据表明，HIV 相关的黏膜上皮 TJ 破坏可能增强 HPV 感染和随后 HPV 相关肿瘤的发展。
