Formation of nuclear CPSF6/CPSF5 biomolecular condensates upon HIV-1 entry into the nucleus is important for productive infection DOI Creative Commons
Charlotte Luchsinger, Kyeongeun Lee, Gonzalo A. Mardones

и другие.

Scientific Reports, Год журнала: 2023, Номер 13(1)

Опубликована: Июль 6, 2023

The early events of HIV-1 infection involve the transport viral core into nucleus. This event triggers translocation CPSF6 from paraspeckles nuclear speckles forming puncta-like structures. Our investigations revealed that neither integration nor reverse transcription is required for formation Moreover, viruses without genome are competent induction In agreement with notion induced structures biomolecular condensates, we showed osmotic stress and 1,6-hexanediol disassembly condensates. Interestingly, replacing by isotonic media re-assemble condensates in cytoplasm cell. To test whether were important utilized hypertonic stress, which prevents during infection. Remarkably, preventing inhibits wild type but not bearing capsid changes N74D A77V, do form infection1,2. We also investigated functional partners recruited to upon experiments CPSF5, CPSF7, co-localized found containing CPSF6/CPSF5 human T cells primary macrophages Additionally, observed cofactor LEDGF/p75 distribution surrounds Overall, our work demonstrated CPSF5 viruses.

Язык: Английский

Liquid-liquid phase separation of nucleocapsid proteins during SARS-CoV-2 and HIV-1 replication DOI Creative Commons

Bao-An Chau,

Venessa Chen,

Alan Cochrane

и другие.

Cell Reports, Год журнала: 2022, Номер 42(1), С. 111968 - 111968

Опубликована: Дек. 26, 2022

The leap of retroviruses and coronaviruses from animal hosts to humans has led two ongoing pandemics tens millions deaths worldwide. Retrovirus coronavirus nucleocapsid proteins have been studied extensively as potential drug targets due their central roles in virus replication, among which is capacity bind respective genomic RNAs for packaging into nascent virions. This review focuses on fundamental studies these how intrinsic abilities condense through liquid-liquid phase separation (LLPS) contribute viral replication. Therapeutic targeting condensates methodological advances are also described address future questions contributes

Язык: Английский

Процитировано

35
When liquid-liquid phase separation meets viral infections DOI Creative Commons
Wenqiang Wei, Lu Bai, Bing Yan

и другие.

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Авг. 9, 2022

Eukaryotic cells have both membranous and membraneless organelles. While the formation mechanism of organelles is well understood, remains unknown. Many biomolecules in cytoplasm transition from liquid phase to agglutinated are known as liquid-liquid separation (LLPS). The biomolecular agglomerates' physical properties enable them function dynamic compartments that respond external pressures stimuli. Scientists gradually recognized importance during viral infections. LLPS provides a powerful new framework for understanding life cycle replication evasion host immune surveillance. As result, this review focuses on progress research infection regulation provide clues antiviral therapeutic strategies.

Язык: Английский

Процитировано

34
Defining basic rules for hardening influenza A virus liquid condensates DOI Creative Commons
Temitope Akhigbe Etibor, Sílvia Vale-Costa, Sindhuja Sridharan

и другие.

eLife, Год журнала: 2023, Номер 12

Опубликована: Апрель 4, 2023

In biological systems, liquid and solid-like biomolecular condensates may contain the same molecules but their behaviour, including movement, elasticity, viscosity, is different on account of distinct physicochemical properties. As such, it known that phase transitions affect function material properties can be tuned by several factors temperature, concentration, valency. It is, however, unclear if some are more efficient than others at regulating behaviour. Viral infections good systems to address this question as they form de novo part replication programmes. Here, we used influenza A virus (IAV) cytosolic condensates, AKA viral inclusions, provide a proof concept condensate hardening via changes in valency its components altering concentration or temperature cell. Liquid IAV inclusions hardened targeting vRNP (viral ribonucleoprotein) interactions NP (nucleoprotein) oligomerising molecule, nucleozin, both vitro vivo without affecting host proteome abundance nor solubility. This study starting point for understanding how pharmacologically modulate offer opportunities alternative antiviral strategies.

Язык: Английский

Процитировано

24
Cryo-Electron Tomography: The Resolution Revolution and a Surge of In Situ Virological Discoveries DOI Creative Commons
Ye Hong, Yutong Song, Zheyuan Zhang

и другие.

Annual Review of Biophysics, Год журнала: 2023, Номер 52(1), С. 339 - 360

Опубликована: Янв. 31, 2023

The recent proliferation of cryo-electron tomography (cryo-ET) techniques has led to the cryo-ET resolution revolution. Meanwhile, significant efforts have been made improve identification targets in cellular context and throughput cryo-focused ion beam (FIB) milling. Together, these developments a surge situ discoveries on how enveloped viruses are assembled interact with cells infected hosts. In this article, we review advances cryo-ET, high-resolution insights into virus assembly, findings from inside eukaryotic prokaryotic cells.

Язык: Английский

Процитировано

23
Biomolecular condensates: insights into early and late steps of the HIV-1 replication cycle DOI Creative Commons
Francesca Di Nunzio, Vladimir N. Uversky, Andrew J. Mouland

и другие.

Retrovirology, Год журнала: 2023, Номер 20(1)

Опубликована: Апрель 7, 2023

Abstract A rapidly evolving understanding of phase separation in the biological and physical sciences has led to redefining virus-engineered replication compartments many viruses with RNA genomes. Condensation viral, host genomic subgenomic RNAs can take place evade innate immunity response help viral replication. Divergent prompt liquid–liquid (LLPS) invade cell. During HIV there are several steps involving LLPS. In this review, we characterize ability individual partners that assemble into biomolecular condensates (BMCs). Of note, bioinformatic analyses predict models line published observations. Importantly, BMCs contribute function key retroviral For example, reverse transcription takes within nuclear BMCs, called HIV-MLOs while during late steps, nucleocapsid acts as a driver or scaffold recruit client components aid assembly progeny virions. Overall, LLPS infections represents newly described event now appreciated virology field, also be considered an alternative pharmacological target current drug therapies especially when become resistant antiviral treatment.

Язык: Английский

Процитировано

21
Intrinsic factors behind long COVID: IV. Hypothetical roles of the SARS‐CoV‐2 nucleocapsid protein and its liquid–liquid phase separation DOI

Ahmed Eltayeb,

Faisal Al‐Sarraj, Mona G. Alharbi

и другие.

Journal of Cellular Biochemistry, Год журнала: 2024, Номер 125(3)

Опубликована: Фев. 13, 2024

Abstract When the SARS‐CoV‐2 virus infects humans, it leads to a condition called COVID‐19 that has wide spectrum of clinical manifestations, from no symptoms acute respiratory distress syndrome. The initiates damage by attaching ACE‐2 protein on surface endothelial cells line blood vessels and using these as hosts for replication. Reactive oxygen species levels are increased during viral replication, which oxidative stress. About three‐fifths (~60%) people who get infected with eradicate their body after 28 days recover normal activity. However, large fraction (~40%) suffer various (anosmia and/or ageusia, fatigue, cough, myalgia, cognitive impairment, insomnia, dyspnea, tachycardia) beyond 12 weeks diagnosed syndrome long COVID. Long‐term studies in group contracted have been contrasted noninfected matched people. A subset can be distinguished set cytokine markers persistent, low‐grade inflammation often self‐report two or more bothersome symptoms. No medication alleviate efficiently. Coronavirus nucleocapsid proteins investigated extensively potential drug targets due key roles among is ability bind respective genomic RNAs incorporation into emerging virions. This review highlights basic its undergo liquid–liquid phase separation. We hypothesize this separation may contribute hypothesis unlocks new investigation angles could potentially open novel avenues better understanding COVID treating condition.

Язык: Английский

Процитировано

9
Fluorescent protein tags affect the condensation properties of a phase-separating viral protein DOI
Russell J. R. Barkley, Jack C. Crowley, Andrew J. Brodrick

и другие.

Molecular Biology of the Cell, Год журнала: 2024, Номер 35(7)

Опубликована: Май 29, 2024

Fluorescent protein (FP) tags are extensively used to visualize and characterize the properties of biomolecular condensates despite a lack investigation into effects these on phase separation. Here, we characterized dynamic µNS, viral hypothesized undergo separation main component mammalian orthoreovirus factories. Our interest in sequence determinants nucleation process µNS led us compare size density formed by FP::µNS untagged protein. We found an FP-dependent increase droplet density, which suggests that FP can promote condensation. To further assess effect formation, fused mutants show could variably induce otherwise noncondensing proteins. By comparing fluorescent constructs with identified mNeonGreen as least artifactual tag minimally perturbed These results some more suitable for visualizing characterizing minimal experimental artifacts.

Язык: Английский

Процитировано

8
RNA and condensates: Disease implications and therapeutic opportunities DOI Creative Commons

Tina W. Han,

Bede Portz, Richard A. Young

и другие.

Cell chemical biology, Год журнала: 2024, Номер 31(9), С. 1593 - 1609

Опубликована: Сен. 1, 2024

Язык: Английский

Процитировано

7
Rotavirus research: 2014–2020 DOI
Sarah Caddy, Guido Papa, Alexander Borodavka

и другие.

Virus Research, Год журнала: 2021, Номер 304, С. 198499 - 198499

Опубликована: Июль 2, 2021

Язык: Английский

Процитировано

41
Scaffolding viral protein NC nucleates phase separation of the HIV-1 biomolecular condensate DOI Creative Commons
Anne Monette,

Meijuan Niu,

Maya Nijhoff Asser

и другие.

Cell Reports, Год журнала: 2022, Номер 40(8), С. 111251 - 111251

Опубликована: Авг. 1, 2022

Membraneless biomolecular condensates (BMCs) contribute to the replication of a growing number viruses but remain be functionally characterized. Previously, we demonstrated that pan-retroviral nucleocapsid (NC) proteins phase separated into regulating virus assembly. Here discover intrinsically disordered human immunodeficiency virus-type 1 (HIV-1) core condense with viral genomic RNA (vRNA) assemble as BMCs attaining geometry characteristic reverse transcription complexes. We explore predisposition, mechanisms, and pharmacologic sensitivity HIV-1 in living cells. vRNA-interacting NC were found scaffolds onto which client capsid, transcriptase, integrase assemble. exhibit fundamental characteristics are drug-sensitive. Lastly, protease-mediated maturation Gag Gag-Pol precursor yield abundant visible This study redefines components fluid advances our understanding nature cores during ingress.

Язык: Английский

Процитировано

28