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探索 HIV-1 成熟:抗病毒药物开发的新前沿。

Exploring HIV-1 Maturation: A New Frontier in Antiviral Development.

机构信息

Department Biology, College of Arts and Sciences, American University, Washington, DC 20016, USA.

Virus-Cell Interaction Section, HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MS 21702, USA.

出版信息

Viruses. 2024 Sep 6;16(9):1423. doi: 10.3390/v16091423.


DOI:10.3390/v16091423
PMID:39339899
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11437483/
Abstract

HIV-1 virion maturation is an essential step in the viral replication cycle to produce infectious virus particles. Gag and Gag-Pol polyproteins are assembled at the plasma membrane of the virus-producer cells and bud from it to the extracellular compartment. The newly released progeny virions are initially immature and noninfectious. However, once the Gag polyprotein is cleaved by the viral protease in progeny virions, the mature capsid proteins assemble to form the fullerene core. This core, harboring two copies of viral genomic RNA, transforms the virion morphology into infectious virus particles. This morphological transformation is referred to as maturation. Virion maturation influences the distribution of the Env glycoprotein on the virion surface and induces conformational changes necessary for the subsequent interaction with the CD4 receptor. Several host factors, including proteins like cyclophilin A, metabolites such as IP6, and lipid rafts containing sphingomyelins, have been demonstrated to have an influence on virion maturation. This review article delves into the processes of virus maturation and Env glycoprotein recruitment, with an emphasis on the role of host cell factors and environmental conditions. Additionally, we discuss microscopic technologies for assessing virion maturation and the development of current antivirals specifically targeting this critical step in viral replication, offering long-acting therapeutic options.

摘要

HIV-1 病毒粒子成熟是病毒复制周期中的一个必要步骤,可产生感染性病毒颗粒。Gag 和 Gag-Pol 多聚蛋白在病毒产生细胞的质膜上组装,并从质膜出芽到细胞外腔。新释放的子代病毒粒子最初是不成熟和无感染力的。然而,一旦子代病毒粒子中的病毒蛋白酶切割 Gag 多聚蛋白,成熟的衣壳蛋白就会组装形成富勒烯核心。这个核心含有两份病毒基因组 RNA,将病毒粒子形态转变为感染性病毒颗粒。这种形态转变称为成熟。病毒粒子成熟影响 Env 糖蛋白在病毒粒子表面的分布,并诱导随后与 CD4 受体相互作用所需的构象变化。已经证明几种宿主因子,包括蛋白如亲环素 A、代谢物如 IP6 和含有神经鞘磷脂的脂筏,对病毒粒子成熟有影响。本文深入探讨了病毒成熟和 Env 糖蛋白募集的过程,重点介绍了宿主细胞因子和环境条件的作用。此外,我们还讨论了评估病毒粒子成熟的微观技术以及专门针对病毒复制这一关键步骤的现有抗病毒药物的开发,为长效治疗提供了选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d7b/11437483/66e4ef8e8a6c/viruses-16-01423-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d7b/11437483/14ce744ca241/viruses-16-01423-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d7b/11437483/bf499297972f/viruses-16-01423-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d7b/11437483/ffe700538158/viruses-16-01423-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d7b/11437483/66e4ef8e8a6c/viruses-16-01423-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d7b/11437483/14ce744ca241/viruses-16-01423-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d7b/11437483/bf499297972f/viruses-16-01423-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d7b/11437483/ffe700538158/viruses-16-01423-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d7b/11437483/66e4ef8e8a6c/viruses-16-01423-g004.jpg

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[2]
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[3]
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本文引用的文献

[1]
The HIV-1 capsid serves as a nanoscale reaction vessel for reverse transcription.

PLoS Pathog. 2024-9

[2]
Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women.

N Engl J Med. 2024-10-3

[3]
Evaluating HIV-1 Infectivity and Virion Maturation across Varied Producer Cells with a Novel FRET-Based Detection and Quantification Assay.

Int J Mol Sci. 2024-6-10

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Imaging HIV-1 Nuclear Import, Uncoating, and Proviral Transcription.

Methods Mol Biol. 2024

[5]
Pharmacologic hyperstabilisation of the HIV-1 capsid lattice induces capsid failure.

Elife. 2024-2-13

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Antivir Ther. 2023-12

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mBio. 2024-1-16

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HIV-1 Env trimers asymmetrically engage CD4 receptors in membranes.

Nature. 2023-11

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Cabotegravir + Rilpivirine Long-Acting Injections for HIV Treatment in the US: Real World Data from the OPERA Cohort.

Infect Dis Ther. 2023-12

[10]
Lenacapavir: A novel injectable HIV-1 capsid inhibitor.

Int J Antimicrob Agents. 2024-1

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