gp120-derived amyloidogenic peptides form amyloid fibrils that increase HIV-1 infectivity  

作　　者：Suiyi Tan Wenjuan Li Chan Yang Qingping Zhan Kunyu Lu Jun Liu Yong-Mei Jin Jin-Song Bai Lin Wang Jinqing Li Zhaofeng Li Fei Yu Yu-Ye Li Yue-Xun Duan Lu Lu Tong Zhang Jiaqi Wei Lin Li Yong-Tang Zheng Shibo Jiang Shuwen Liu 

机构地区：[1]Guangdong-Hong Kong-Macao Joint Laboratory for New Drug Screening,NMPA Key Laboratory for Research and Evaluation of Drug Metabolism,Guangdong Provincial Key Laboratory of New Drug Screening,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou,510515,China [2]Department of Infectious Disease,The Third People’s Hospital of Kunming,Kunming,650041,China [3]Department of Pathology,The Third People’s Hospital of Kunming,Kunming,650041,China [4]Hebei Key Laboratory of Analysis and Control of Zoonotic Pathogenic Microorganism,College of Life Sciences,Hebei Agricultural University,Baoding,071001,China [5]Department of Dermatology and Venereology,First Affiliated Hospital of Kunming Medical University,Kunming,650032,China [6]Yunnan Provincial Infectious Disease Hospital,Kunming,650301,China [7]Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS),Shanghai Institute of Infectious Disease and Biosecurity,School of Basic Medical Sciences,Fudan University,Shanghai,200032,China [8]Beijing Key Laboratory for HIV/AIDS Research,Clinical and Research Center for Infectious Diseases,Beijing Youan Hospital,Capital Medical University,Beijing,100069,China [9]State Key Laboratory of Genetic Evolution&Animal Models,Key Laboratory of Bioactive Peptides of Yunnan Province,KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases,Center for Biosafety Mega-Science,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming,Yunnan,650223,China

出　　处：《Cellular & Molecular Immunology》2024年第5期479-494,共16页中国免疫学杂志（英文版）

基　　金：supported by grants from the Natural Science Foundation of China(82072276 and 81772194 to ST,82073898 and 31370781 to SL,and 81630090 to SJ).

摘　　要：Apart from mediating viral entry,the function of the free HIV-1 envelope protein(gp120)has yet to be elucidated.Our group previously showed that EP2 derived from oneβ-strand in gp120 can form amyloid fibrils that increase HIV-1 infectivity.Importantly,gp120 contains~30β-strands.We examined whether gp120 might serve as a precursor protein for the proteolytic release of amyloidogenic fragments that form amyloid fibrils,thereby promoting viral infection.Peptide array scanning,enzyme degradation assays,and viral infection experiments in vitro confirmed that manyβ-stranded peptides derived from gp120 can indeed form amyloid fibrils that increase HIV-1 infectivity.These gp120-derived amyloidogenic peptides,or GAPs,which were confirmed to form amyloid fibrils,were termed gp120-derived enhancers of viral infection(GEVIs).GEVIs specifically capture HIV-1 virions and promote their attachment to target cells,thereby increasing HIV-1 infectivity.Different GAPs can cross-interact to form heterogeneous fibrils that retain the ability to increase HIV-1 infectivity.GEVIs even suppressed the antiviral activity of a panel of antiretroviral agents.Notably,endogenous GAPs and GEVIs were found in the lymphatic fluid,lymph nodes,and cerebrospinal fluid(CSF)of AIDS patients in vivo.Overall,gp120-derived amyloid fibrils might play a crucial role in the process of HIV-1 infectivity and thus represent novel targets for anti-HIV therapeutics.

关 键 词：HIV-1 GP120 Amyloid fibril Enhancement of viral infectivity 

分 类 号：R512.91[医药卫生—内科学]