气候变化领域集成服务门户(CCPortal): HIV-1 cores retain their integrity until minutes before uncoating in the nucleus

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DOI	10.1073/pnas.2019467118
	HIV-1 cores retain their integrity until minutes before uncoating in the nucleus
	Li C.; Burdick R.C.; Nagashima K.; Hu W.-S.; Pathak V.K.
发表日期	2021
ISSN	00278424
卷号	118 期号:10
英文摘要	We recently reported that HIV-1 cores that retained >94% of their capsid (CA) protein entered the nucleus and disassembled (uncoated) near their integration site <1.5 h before integration. However, whether the nuclear capsids lost their integrity by rupturing or a small loss of CA before capsid disassembly was unclear. Here, we utilized a previously reported vector in which green fluorescent protein is inserted in HIV-1 Gag (iGFP); proteolytic processing efficiently releases GFP, some of which remains trapped inside capsids and serves as a fluid phase content marker that is released when the capsids lose their integrity. We found that nuclear capsids retained their integrity until shortly before integration and lost their GFP content marker ∼1 to 3 min before loss of capsid-associated mRuby-tagged cleavage and polyadenylation specificity factor 6 (mRuby-CPSF6). In contrast, loss of GFP fused to CA and mRuby-CPSF6 occurred simultaneously, indicating that viral cores retain their integrity until just minutes before uncoating. Our results indicate that HIV-1 evolved to retain its capsid integrity and maintain a separation between macromolecules in the viral core and the nuclear environment until uncoating occurs just before integration. These observations imply that intact HIV-1 capsids are imported through nuclear pores; that reverse transcription occurs in an intact capsid; and that interactions between the preintegration complex and LEDGF/p75, and possibly other host factors that facilitate integration, must occur during the short time period between loss of capsid integrity and integration. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Capsid; Core integrity; HIV-1; Nuclear import; Uncoating
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180418
作者单位	Viral Mutation Section, HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, United States; Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, United States; Viral Recombination Section, HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, United States
推荐引用方式 GB/T 7714	Li C.,Burdick R.C.,Nagashima K.,et al. HIV-1 cores retain their integrity until minutes before uncoating in the nucleus[J],2021,118(10).
APA	Li C.,Burdick R.C.,Nagashima K.,Hu W.-S.,&Pathak V.K..(2021).HIV-1 cores retain their integrity until minutes before uncoating in the nucleus.Proceedings of the National Academy of Sciences of the United States of America,118(10).
MLA	Li C.,et al."HIV-1 cores retain their integrity until minutes before uncoating in the nucleus".Proceedings of the National Academy of Sciences of the United States of America 118.10(2021).