Anti-L1 antibody-bound HPV16 pseudovirus is degraded intracellularly via TRIM21/proteasomal pathway

作者全名:"Li, Meiying; Huang, Jianmei; Zhu, Yi; Huang, Ziyi; Zhang, Guonan; Huang, Jianming"

作者地址:"[Li, Meiying; Huang, Jianming] Sichuan Canc Inst, Dept Biochem & Mol Biol, Chengdu 610041, Peoples R China; [Huang, Jianmei; Zhu, Yi; Zhang, Guonan] Univ Elect Sci & Technol China, Sch Med, Sichuan Canc Hosp, Dept Gynecol Oncol, Chengdu 610041, Peoples R China; [Zhu, Yi] Sichuan Canc Hosp, Dept Ultrasound, Chengdu 610041, Peoples R China; [Huang, Ziyi] Chongqing Med Univ, Dept Bioinformat, Basic Med Coll, Chongqing, Peoples R China"

通信作者:"Huang, JM (通讯作者),Sichuan Canc Inst, Dept Biochem & Mol Biol, Chengdu 610041, Peoples R China."

来源:VIROLOGY JOURNAL

ESI学科分类:MICROBIOLOGY

WOS号:WOS:000800562400003

JCR分区:Q2

影响因子:4.8

年份:2022

卷号:19

期号:1

开始页: 

结束页: 

文献类型:Article

关键词:HPV16; Persistent infection; Cervical cancer; TRIM21; Anti-L1 antibody; Intracellular neutralization

摘要:"Background: Persistent HPV16 infection is the leading risk factor for developing cervical cancer. Anti-L1 antibodies against HPV16 produced in HPV16 infections play diverse roles in the clearance of virus infection and prevention of persistence. It has been implicated that the cervicovaginal squamous epithelial cells actually express TRIM21 and that some HPV16 particles could escape leaky endosomal compartment into the cytosol and that Fc receptor TRIM21 directly neutralize infection by targeting antibody-opsonized viruses for proteasomal degradation. We explored whether anti-L1 antibody opsonized HPV16 pseudovirus (PsV) entered into the cytosol could be neutralized by TRIM21-mediated activation of a proteasomal pathway to reduce the chance of persistent HPV16 infection. Methods: HPV16 PsV were generated and extracted in HEK 293FT cells co-transfected with pcDNA3.1-eGFP and p16sheLL plasmids according to the standard protocol. The HPV16 PsV with capsid protein L1 was characterized by fluorescence microscopy and western blot, and the HPV16 PsV titer and anti-L1-bound PsV entry efficiency were detected by flow cytometry. The expressions of transcription factors (TF) and cytokines elicited by the TRIM21-activated proteasomal pathway were confirmed by dual-luciferase reporter assay and RT-qPCR. The changes in HPV16 PsV load with or without inhibitors in the infected HEK 293FT cells were determinated by qPCR. Results: Simultaneous transfection with pcDNA3.1-eGFP and p16sheLL plasmids into the HEK 293FT cells resulted in the self-assembly of HPV16 PsV with capsid protein L1. Both HPV16 PsV and anti-L1-bound HPV16 PsV could infect HEK 293FT cells. Anti-L1-bound PsV up-regulated TRIM21 mediated-activation of proteasome and increased expressions of TF and cytokines in the infected cells where HPV16 PsV load reduced by similar to 1000-fold in the presence of anti-L1 antibody, but inhibition of proteasomal activity increased HPV16 PsV load. Conclusion: Our preliminary results indicate that anti-L1 antibody entered with HPV16 PsV into the cells could mediate degradation of HPV16 PsV by TRIM21-activated proteasomal pathway intracellularly, giving anti-capsid protein L1 antibody a role in host defense of persistent HPV16 infection."

基金机构:Sichuan Key Research and Development Project from Sichuan Provincial Science & Technology Program [2019YFS0405]

基金资助正文:This work was supported by grants from Sichuan Key Research and Development Project from Sichuan Provincial Science & Technology Program (Grant No. 2019YFS0405).