Department of Microbiology, University of Colorado School of Medicine, Aurora, CO 80045, United States.
Virology. 2013 Mar 1;437(1):12-9. doi: 10.1016/j.virol.2012.12.004. Epub 2013 Jan 4.
Human papillomavirus (HPV) infection is severely limited in its natural host, primary human keratinocytes. Our data show HPV infectivity in primary keratinocytes is over 100- and 1,000-fold lower than in established keratinocyte cell lines NIKS and HaCaT, respectively. Here, we show that the basal level of autophagy in primary human foreskin keratinocytes (HFKs) is higher than in immortalized keratinocytes, and that HPV16 virions significantly induce autophagy in HFKs. Interestingly, HPV16 infectivity is dramatically enhanced by knockdown of essential autophagy genes as well as biochemical inhibition of autophagy. The increase in HPV16 infectivity by autophagy inhibition is most significant in HFKs, showing an inverse correlation with basal HPV16 infectivity in HFK, NIKS, HaCaT, and 293FT cells. Further, inhibition of autophagy delays degradation of HPV16 capsid proteins during virus trafficking, indicating that host autophagy induced by HPV16 virions inhibits infection of primary keratinocytes through rapid degradation of viral capsid proteins.
人乳头瘤病毒（HPV）在其自然宿主原发性人角质形成细胞中感染受到严重限制。我们的数据表明，HPV 在原代角质形成细胞中的感染性分别比已建立的角质形成细胞系 NIKS 和 HaCaT 低 100 倍和 1000 倍。在这里，我们表明原代人包皮角质形成细胞（HFKs）中的自噬基础水平高于永生化角质形成细胞，并且 HPV16 病毒粒子在 HFKs 中显著诱导自噬。有趣的是，HPV16 感染性通过必需自噬基因的敲低以及自噬的生化抑制显著增强。自噬抑制对 HPV16 感染性的增加在 HFKs 中最为显著，与 HFK、NIKS、HaCaT 和 293FT 细胞中基础 HPV16 感染性呈负相关。此外，自噬的抑制会延迟病毒运输过程中 HPV16 衣壳蛋白的降解，表明 HPV16 病毒粒子诱导的宿主自噬通过快速降解病毒衣壳蛋白抑制原代角质形成细胞的感染。
