论文题目: | Gp120-derived Amyloidogenic Peptides Form Amyloid Fibrils that Increase HIV-1 Infectivity |
作者: | Suiyi Tan, Wenjuan Li等 |
联系作者: | liusw@smu.edu.cn |
发表年度: | 2024 |
DOI: | DOI: 10.1038/s41423-024-01144-y |
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 one beta-strand in gp120 can form amyloid fibrils that increase HIV-1 infectivity. Importantly, gp120 contains similar to 30 beta-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 many beta-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. |
刊物名称: | Cellular & Molecular Immunology |
论文出处: | https://www.nature.com/articles/s41423-024-01144-y |
影响因子: | 24.1(2022IF) |