Department of Dermatology and Venereology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Department of Microbiology and Parasitology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Zhejiang University, Hangzhou, China.
Aging (Albany NY). 2020 Nov 16;12(22):23017-23028. doi: 10.18632/aging.104046.
Human papillomavirus type 11 (HPV11) is one of the main causes of condyloma acuminatum, a widespread sexually transmitted disease. During infection of its primary target cell, keratinocytes, it is likely to encounter the autophagy pathway, which is an intracellular maintenance process that is also able to target invading pathogens. It is currently unknown whether HPV11 is targeted by autophagy or whether it is able to escape autophagy-mediated killing. Here, we investigated the autophagy response during HPV11 pseudovirion (PsV) entry in human keratinocytes. Transmission electron microscopy showed that intracellular PsVs were sequestered in lumen of double-membrane autophagosomes that subsequently appeared to fuse with lysosomes, while confocal microscopy showed induction LC3 puncta, the hallmark of induced autophagy activity. Furthermore, quantitative infection assays showed that high autophagy activity resulted in reduced HPV11 PsV infectivity. Therefore, the autophagy pathway seemed to actively target invading HPV11 PsVs for destruction in the autolysosome. Western analysis on the phosphorylation state of autophagy regulators and upstream pathways indicated that autophagy was activated through interplay between Erk and Akt signaling. In conclusion, autophagy functions as a cellular protection mechanism against intracellular HPV11 and therefore therapies that stimulate autophagy may prevent recurrent condyloma acuminatum by helping eliminate latent HPV11 infections.
人乳头瘤病毒 11 型（HPV11）是导致尖锐湿疣的主要原因之一，尖锐湿疣是一种广泛传播的性传播疾病。在感染其主要靶细胞角质形成细胞时，它可能会遇到自噬途径，自噬是一种细胞内维持过程，也能够靶向入侵的病原体。目前尚不清楚 HPV11 是否被自噬靶向，或者它是否能够逃避自噬介导的杀伤。在这里，我们研究了 HPV11 假病毒（PsV）在人角质形成细胞中进入时的自噬反应。透射电子显微镜显示，细胞内的 PsVs 被隔离在双层自噬体的腔中，随后似乎与溶酶体融合，而共聚焦显微镜显示诱导 LC3 斑点，这是诱导自噬活性的标志。此外，定量感染实验表明，高自噬活性导致 HPV11 PsV 感染性降低。因此，自噬途径似乎主动靶向入侵的 HPV11 PsVs 以在自溶酶体中进行破坏。自噬调节剂和上游途径磷酸化状态的 Western 分析表明，自噬通过 Erk 和 Akt 信号的相互作用而被激活。总之，自噬作为一种针对细胞内 HPV11 的细胞保护机制而发挥作用，因此刺激自噬的疗法可能通过帮助消除潜伏的 HPV11 感染来预防尖锐湿疣的复发。
