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Nuclear pore blockade reveals that HIV-1 completes reverse transcription and uncoating in the nucleus
Open accessAbstract
Retroviral infection involves the reverse transcription of the viral RNA genome into DNA, which is subsequently integrated into the host cell genome. Human immunodeficiency virus type 1 (HIV-1) and other lentiviruses mediate the infection of non-dividing cells through the ability of the capsid protein 1 to engage the cellular nuclear import pathways of the target cell and mediate their nuclear translocation through components of the nuclear pore complex 2-4. Although recent studies have observed the presence of the capsid protein in the nucleus during infection 5-8, reverse transcription and disassembly of the viral core have conventionally been considered to be cytoplasmic events. Here, we use an inducible nuclear pore complex blockade to monitor the kinetics of HIV-1 nuclear import and define the biochemical staging of these steps of infection. Surprisingly, we observe that nuclear import occurs with relatively rapid kinetics (<5 h) and precedes the completion of reverse transcription in target cells, demonstrating that reverse transcription is completed in the nucleus. We also observe that HIV-1 remains susceptible to the capsid-destabilizing compound PF74 following nuclear import, revealing that uncoating is completed in the nucleus. Additionally, we observe that certain capsid mutants are insensitive to a Nup62-mediated nuclear pore complex blockade in cells that potently block infection by wild-type capsid, demonstrating that HIV-1 can use distinct nuclear import pathways during infection. These studies collectively define the spatio-temporal staging of critical steps of HIV-1 infection and provide an experimental system to separate and thereby define the cytoplasmic and nuclear stages of infection by other viruses.
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“Beyond its structural role, CA participates in multiple stages of the viral replication cycle, including reverse transcription (RT), cytoplasmic transport via microtubules, uncoating of the viral pre-integration complex, nuclear import, integration, and viral assembly (12, 13).”
From Research progress on HIV-1 structural proteins and antiviral therapies (2026) · cites this paper as [12]
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“However, using HIV-1 as a model, it has now been established that reverse transcription begins in the cytoplasm and is completed within the intact CA in the nucleus (Fig. 5).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Dharan et al. 2020
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“Recent studies have shown that in HIV-1, the intact CA containing the reverse transcription complex, which includes dimerized RNA, RT, CA, NC, IN, Vpr, and host factors such as APOBEC3G gains access to the nucleus (Fig. 5) (Burdick et al. 2020, Dharan et al. 2020, Selyutina et al. 2020, Li et al. 2021, Müller et al. 2021).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Dharan et al. 2020
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“some recent studies report the presence of intact CA and CA-like structures inside the nucleus, challenging the prevailing notions about retroviral CA uncoating”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Dharan et al. 2020
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“uncoating occurs near the integration site ~1.5 hours before integration due to the mounting physical pressure exerted by the newly reverse transcribed DNA”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Dharan et al. 2020
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“In contrast to this, HIV-1 PICs have been found to contain CA molecules; furthermore, some recent studies report the presence of intact CA and CA-like structures inside the nucleus, challenging the prevailing notions about retroviral CA uncoating (Burdick et al. 2020, Dharan et al. 2020, Selyutina et al. 2020, Müller et al. 2021).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Dharan et al. 2020
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“Thus, for at least HIV-1, once the CA is inside the nucleus, reverse transcription and PIC formation are completed, and uncoating occurs near the integration site ~1.5 hours before integration due to the mounting physical pressure exerted by the newly reverse transcribed DNA (Fig. 5) (Rankovic et al. 2017, Burdick et al. 2020, Dharan et al. 2020, Li et al. 2021, Müller et al. 2021, Yu et al. 2022)”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Dharan et al. 2020
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Citations
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Self-citation
Cited by
Sorted by citations
Cone-shaped HIV-1 capsids are transported through intact nuclear pores
Žíla, V., Margiotta, E., Turoňová, B., Müller, T. G., Zimmerli, C. E., Mattei, S., Allegretti, M., Börner, K., Rada, J., Müller, B., et al. (2021) · Cell · doi:10.1016/j.cell.2021.01.025 · Cited by 361
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. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2019467118 · Cited by 168
“We and others have recently reported that time-of-addition assays with capsid inhibitors PF74 and GS-CA1 (25, 30, 54) inhibited viral replication and resulted in disassembly of nuclear viral cores (25), supporting the view that premature un-coating of the viral core prevents formation of a functional PIC that can inte…”
InfluentialLiquid Biomolecular Condensates and Viral Lifecycles: Review and Perspectives
Etibor, T. A., Yamauchi, Y., & Amorim, M. J. (2021) · Viruses · doi:10.3390/v13030366 · Cited by 134
“The viral lifecycle of HIV is complex, the +ssRNA is reverse transcribed to cDNA, the cDNA is integrated in the genome, and upon being transcribed, both mRNAs and genomic RNA are transported to the cytosol [205,206] to produce viral proteins Gag polyprotein precursor (also known as Pr55Gag), GagPol polyprotein precurs…”
BackgroundMüller, T. G., Žíla, V., Peters, K., Schifferdecker, S., Stanić, M., Lucic, B., Laketa, V., Lušić, M., Müller, B., & Kräusslich, H. (2021) · eLife · doi:10.7554/elife.64776 · Cited by 129
HIV-1 Maturation: Lessons Learned from Inhibitors
Kleinpeter, A. B., & Freed, E. O. (2020) · Viruses · doi:10.3390/v12090940 · Cited by 106
“Although early models proposed that the capsid uncoats soon after membrane fusion, accumulating evidence now suggests that upon release into the cytoplasm, the capsid remains intact, or nearly intact, as it traffics to the nuclear envelope [35,36] and into the nucleus [37,38] (Figure 1).”
BackgroundNuclear Capsid Uncoating and Reverse Transcription of HIV-1
Müller, T. G., Žíla, V., Müller, B., & Kräusslich, H. (2022) · Annual Review of Virology · doi:10.1146/annurev-virology-020922-110929 · Cited by 109
Passage of the HIV capsid cracks the nuclear pore
Kreysing, J. P., Heidari, M., Žíla, V., Cruz-León, S., Obarska-Kosińska, A., Laketa, V., Rohleder, L., Welsch, S., Köfinger, J., Turoňová, B., et al. (2025) · Cell · doi:10.1016/j.cell.2024.12.008 · Cited by 100
Clustering and reverse transcription of HIV‐1 genomes in nuclear niches of macrophages
Rensen, E., Mueller, F., Scoca, V., Parmar, J. J., Souque, P., Zimmer, C., & Nunzio, F. D. (2020) · The EMBO Journal · doi:10.15252/embj.2020105247 · Cited by 99
“We note that two recent studies published during the revision of this paper reported similar findings (Francis et al , 2020; Dharan et al , 2020).”
van Heuvel, Y., Schatz, S., Rosengarten, J. F., & Stitz, J. (2022) · Toxins · doi:10.3390/toxins14020138 · Cited by 127
“Upon nucleoplasm entry, the capsid partially disassembles, releasing the CA interior [40,41].”
BackgroundResultStructure, Function, and Interactions of the HIV-1 Capsid Protein
Rossi, E., Meuser, M. E., Cunanan, C. J., & Cocklin, S. (2021) · Life · doi:10.3390/life11020100 · Cited by 111
The structural basis for HIV-1 Vif antagonism of human APOBEC3G
Li, Y.-L., Langley, C. A., Azumaya, C. M., Echeverria, I., Chesarino, N. M., Emerman, M., Cheng, Y., & Gross, J. D. (2023) · Nature · doi:10.1038/s41586-023-05779-1 · Cited by 80
Permeability of the HIV-1 capsid to metabolites modulates viral DNA synthesis
Xu, C., Fischer, D. K., Rankovic, S., Li, W., Dick, R. A., Runge, B., Zadorozhnyi, R., Ahn, J., Aiken, C., Polenova, T. E., et al. (2020) · PLoS Biology · doi:10.1371/journal.pbio.3001015 · Cited by 63
“Recent findings indicate that HIV-1 reverse transcription terminates in the nucleus where dNTP concentrations are comparatively high [32,35,36].”
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Pseudotyping Lentiviral Vectors: When the Clothes Make the Virus
Duvergé, A., & Negroni, M. (2020) · Viruses · doi:10.3390/v12111311 · Cited by 65
“The traditional view according to which reverse transcription was completed in the cytoplasm or at the nuclear pore, followed by the dismantling of the capsid core and the import of the preintegration nucleoprotein complex [46–49], has recently been challenged by the observation of intact or almost-intact cores, as we…”
BackgroundSelyutina, A., Hu, P., Miller, S. O., Simons, L. M., Yu, H. J., Hultquist, J. F., Lee, K., KewalRamani, V. N., & Diaz‐Griffero, F. (2021) · iScience · doi:10.1016/j.isci.2021.103593 · Cited by 53
HIV capsid and integration targeting
Engelman, A. N. (2021) · Viruses · doi:10.3390/v13010125 · Cited by 57
The HIV-1 capsid and reverse transcription
Aiken, C., & Rousso, I. Y. (2021) · Retrovirology · doi:10.1186/s12977-021-00566-0 · Cited by 67
“Consistent with recently reported evidence that reverse transcription and uncoating are completed following entry of the HIV-1 core into the target cell nucleus [57, 67, 68], the uncoating trigger may involve a cellular activity, or it could relate to the mechanically induced uncoating we observed in ERT reactions.”
BackgroundFrancis, A. C., Marin, M., Prellberg, M., Palermino-Rowland, K., & Melikyan, G. B. (2020) · Viruses · doi:10.3390/v12111234 · Cited by 58
“Our current work thus confirms and expands upon the recent reports that reverse transcription is completed in the nucleus [9,18,21,72,77].”
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“The inducible NPC blockade system may prove useful to evaluate capsid nuclear import by trapping capsids as they transverse NPCs [11,81].”
BackgroundInfluentialA lysine ring in HIV capsid pores coordinates IP6 to drive mature capsid assembly
Renner, N., Mallery, D. L., Faysal, K. M. R., Peng, W., Jacques, D. A., Böcking, T., & James, L. C. (2021) · PLoS Pathogens · doi:10.1371/journal.ppat.1009164 · Cited by 53
“Reverse transcription is then completed in the nucleus prior to uncoating [8, 9].”
BackgroundModeling HIV-1 nuclear entry with nucleoporin-gated DNA-origami channels
Shen, Q., Feng, Q., Wu, C., Xiong, Q., Tian, T., Yuan, S., Shi, J., Bedwell, G. J., Yang, R., Aiken, C., et al. (2023) · Nature Structural & Molecular Biology · doi:10.1038/s41594-023-00925-9 · Cited by 47
From Entry to Egress: Strategic Exploitation of the Cellular Processes by HIV-1
Ramdas, P., Sahu, A. K., Mishra, T. K., Bhardwaj, V., & Chande, A. G. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.559792 · Cited by 50
Shen, Q., Wu, C., Freniere, C., Tripler, T. N., & Xiong, Y. (2021) · Viruses · doi:10.3390/v13112242 · Cited by 56
“About 8 h after infection, the virus core passed through the NPC [13,20]; meanwhile the late RT products continued to accumulate [12,21], suggesting that nuclear import does not depend on the completion of RT [29,30].”
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HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration
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HIV-induced membraneless organelles orchestrate post-nuclear entry steps
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“While uncoating and reverse transcription have long been thought to occur in the cytoplasm, recent studies have provided evidence that these processes are not completed until after nuclear entry [26,27].”
BackgroundRankovic, S., Deshpande, A., Harel, S., Aiken, C., & Rousso, I. Y. (2021) · Journal of Virology · doi:10.1128/jvi.00166-21 · Cited by 46
Hudait, A., & Voth, G. A. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2313737121 · Cited by 44
“The HIV - 1 capsid is known to interact with several FG - NUPs at the CR, IR, and NR (25–27).”
BackgroundThe capsid lattice engages a bipartite NUP153 motif to mediate nuclear entry of HIV-1 cores
Shen, Q., Kumari, S., Xu, C., Jang, S., Shi, J., Burdick, R. C., Levintov, L., Xiong, Q., Wu, C., Devarkar, S. C., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2202815120 · Cited by 41
“Many FG-NUPs have been reported to interact with the HIV-1 capsid, including NUP358, NUP214, NUP62, and NUP153 (16–21).”
Factors that mold the nuclear landscape of HIV-1 integration
Bedwell, G. J., & Engelman, A. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa1207 · Cited by 42
“Because changes in CA residues can dramatically alter HIV-1’s dependency on specific nuclear import factors, it seems that alternative nuclear import pathways must exist for the PIC (59,72).”
BackgroundHIV-1 uncoating requires long double-stranded reverse transcription products
Burdick, R. C., Morse, M., Rouzina, I. F., Williams, M. C., Hu, W.-S., & Pathak, V. K. (2024) · Science Advances · doi:10.1126/sciadv.adn7033 · Cited by 44
“Recent studies have also shown that capsids remain largely intact and play an indispensable role in supporting efficient reverse transcription ( 19 ) and that reverse transcription is completed in the nucleus ( 10 , 20 – 22 ).”
HIV-1 Capsid Core: A Bullet to the Heart of the Target Cell
Toccafondi, E., Lener, D., & Negroni, M. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.652486 · Cited by 33
HIV-1 capsid variability: viral exploitation and evasion of capsid-binding molecules
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Membraneless organelles restructured and built by pandemic viruses: HIV-1 and SARS-CoV-2
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HIV-1 capsid exploitation of the host microtubule cytoskeleton during early infection
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“…allowing HIV-1 capsids to pass the intact NPC (Zila et al., 2021a), and that HIV-1 uncoating occurs after nuclear import (Burdick et al., 2020; Dharan et al., 2020; Li et al., 2021; Muller et al., 2022; Selyutina et al., 2020), apparently by separation of the viral genome from a broken capsid…”
BackgroundCapsid–host interactions for HIV-1 ingress
Jang, S., & Engelman, A. (2023) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00048-22 · Cited by 37
Combating antimicrobial resistance in malaria, HIV and tuberculosis
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“The viral capsid containing the RNA genome and reverse transcriptase (RT) enzymes is then transported to the nucleus via the nucleopore 191,192 where the RT alternates between the two single-stranded RNA (ssRNA) genome templates to synthesize a single-stranded DNA genome.”
Jennings, J., Shi, J., Varadarajan, J., Jamieson, P. J., & Aiken, C. (2020) · mBio · doi:10.1128/mbio.02820-20 · Cited by 40
“A recent study suggests that nuclear entry precedes the completion of reverse transcription, suggesting that the core/reverse transcription complex responds to a specific nuclear signal or is activated during the process of nuclear entry (8).”
BackgroundThe HIV-1 capsid core is an opportunistic nuclear import receptor
Xue, G., Yu, H. J., Buffone, C., Huang, S., Lee, K., Goh, S. L., Gres, A. T., Guney, M. H., Sarafianos, S. G., Luban, J., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-39146-5 · Cited by 37
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Multimodal Functionalities of HIV-1 Integrase
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The Role of Capsid in HIV-1 Nuclear Entry
Guedán, A., Caroe, E. R., Barr, G. C. R., & Bishop, K. N. (2021) · Viruses · doi:10.3390/v13081425 · Cited by 29
“blocked passage through nuclear pores and measured viral replication kinetics, concluding that reverse transcription completed after nuclear entry [31].”
BackgroundHIV-1 capsid is the key orchestrator of early viral replication
Žíla, V., Müller, T. G., Müller, B., & Kräusslich, H. (2021) · PLoS Pathogens · doi:10.1371/journal.ppat.1010109 · Cited by 32
Molecular Biology and Diversification of Human Retroviruses
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HIV-1 capsid and viral DNA integration
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HIV-1 Persistence and Chronic Induction of Innate Immune Responses in Macrophages
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Examination of the APOBEC3 Barrier to Cross Species Transmission of Primate Lentiviruses
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Lenacapavir disrupts HIV-1 core integrity while stabilizing the capsid lattice
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“…our findings, other studies have shown that the HIV - 1 capsid is intact after nuclear entry and sensitive to capsid inhibitor PF - 3450074 (PF74) ( 8 ), an intact capsid is necessary for reverse transcription ( 9 ), and that reverse transcription is completed in the nucleus ( 4 , 8 , 10 , 11 ).”
HIV‐1 capsids mimic a microtubule regulator to coordinate early stages of infection
da Silva, E. S., Shanmugapriya, S., Malikov, V., Gu, F., Delaney, M. K., & Naghavi, M. H. (2020) · The EMBO Journal · doi:10.15252/embj.2020104870 · Cited by 29
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“In cells, biomolecular condensates increase the local concentration of proteins to improve (1) enzymatic activity by bringing enzyme and substrate together, (2) avidity in low-affinity protein interactions, (3) nucleation for polymers such as actin and tubulin, and (4) cell signaling amplification19.”
BackgroundFunctional Impacts of Epitranscriptomic m6A Modification on HIV-1 Infection
Mishra, T., Phillips, S. L., Huang, S., & Wu, L. J. (2024) · Viruses · doi:10.3390/v16010127 · Cited by 24
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“HIV-1 DNA synthesis terminates in the nucleus ( 9 , 40 , 42 , 98 ) where HIV-induced CPSF6 condensates have been suggested to serve as reverse transcription hubs ( 42 ,44 ).”
BackgroundCryo-electron Microscopy Reveals the Structure of the Nuclear Pore Complex
Tai, L., Yin, G., Sun, F., & Zhu, Y. (2023) · Journal of Molecular Biology · doi:10.1016/j.jmb.2023.168051 · Cited by 26
IP6‐stabilised HIV capsids evade cGAS/STING‐mediated host immune sensing
Papa, G., Albecka, A., Mallery, D. L., Vaysburd, M., Renner, N., & James, L. C. (2023) · EMBO Reports · doi:10.15252/embr.202256275 · Cited by 26
“Again, functional and imaging data agree that the final stages of DNA synthesis occur in the nucleus itself, immediately prior to uncoating and integration (Dharan et al , 2020; Francis et al , 2020; Selyutina et al , 2020).”
Localization and functions of native and eGFP-tagged capsid proteins in HIV-1 particles
Francis, A. C., Cereseto, A., Singh, P. K., Shi, J., Poeschla, E. M., Engelman, A., Aiken, C., & Melikyan, G. B. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1010754 · Cited by 24
Viruses in the NucleusPreprint
Lucic, B., de Castro, I. J., & Lušić, M. (2021) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a039446 · Cited by 26
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Cyclic GMP-AMP synthase recognizes the physical features of DNA
Dong, L., Hou, Y.-R., Xu, N., Gao, X., Sun, Z., Yang, Q., & Wang, L. (2024) · Acta Pharmacologica Sinica · doi:10.1038/s41401-024-01369-7 · Cited by 21
“However, Dharan et al. reported that both reverse transcription and uncoating of HIV-1 occur in the nucleus [73].”
Vpr Is a VIP: HIV Vpr and Infected Macrophages Promote Viral Pathogenesis
Lubow, J., & Collins, K. L. (2020) · Viruses · doi:10.3390/v12080809 · Cited by 26
The DEAD box RNA helicase DDX42 is an intrinsic inhibitor of positive‐strand RNA viruses
Bonaventure, B., Rebendenne, A., Valadão, A. L. C., Arnaud‐Arnould, M., Gracias, S., García-de-Gracia, F., McKellar, J., Labaronne, E., Tauziet, M., Vivet‐Boudou, V., et al. (2022) · EMBO Reports · doi:10.15252/embr.202154061 · Cited by 20
“Indeed, our PLA assays showed a close proximity between DDX42 and HIV-1 Capsid, which is a viral protein recently shown to remain associated with reverse transcription complexes until proviral DNA integration in the nucleus (Peng et al , 2014; Burdick et al , 2020; Dharan et al , 2020).”
Ay, S., & Nunzio, F. D. (2023) · Journal of Molecular Biology · doi:10.1016/j.jmb.2023.168094 · Cited by 20
In vivo HIV-1 nuclear condensates safeguard against cGAS and license reverse transcription
Ay, S., Burlaud‐Gaillard, J., Gazi, A. D., Tatirovsky, E., Cuche, C., Diana, J., Scoca, V., Santo, J. P. D., Roingeard, P., Mammano, F., et al. (2024) · The EMBO Journal · doi:10.1038/s44318-024-00316-w · Cited by 23
“The fi nal product of reverse transcription is dsDNA, formed in the host nucleus (Burdick et al, 2020; Dharan et al, 2020; Rensen et al, 2021; Scoca et al, 2022; Selyutina et al, 2020).”
Silencing of Unintegrated Retroviral DNAs
Goff, S. P. (2021) · Viruses · doi:10.3390/v13112248 · Cited by 18
“Finally, we note that HIV-1 reverse transcription may begin in the cytoplasm, but it has been recently revealed that it is completed only within the nucleus, after import of the RTC into the nucleus, and perhaps only very briefly before the time of DNA integration [40].”
Zaongo, S. D., Ouyang, J., Chen, Y., Jiao, Y., Wu, H., & Chen, Y. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.853346 · Cited by 20
“tetracyclic antibiotic, aphidicolin (37).”
Complex Relationships between HIV-1 Integrase and Its Cellular Partners
Rozina, A., Anisenko, A. N., Kikhai, T. F., Silkina, M. O., & Gottikh, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232012341 · Cited by 22
The HIV-1 Capsid: From Structural Component to Key Factor for Host Nuclear Invasion
Scoca, V., & Nunzio, F. D. (2021) · Viruses · doi:10.3390/v13020273 · Cited by 26
“Another recent study, exploiting NPC blockade, showed that HIV-1 crosses the nuclear envelope (NE) in less than 5 h post infection [92] and supports that completion of both reverse transcription and uncoating follow the nuclear import.”
BackgroundVisualizing HIV-1 Capsid and Its Interactions with Antivirals and Host Factors
Wilbourne, M., & Zhang, P. (2021) · Viruses · doi:10.3390/v13020246 · Cited by 22
Imaging Viral Infection by Fluorescence Microscopy: Focus on HIV-1 Early Stage
Mukherjee, S., Boutant, E., Réal, É., Mély, Y., & Anton, H. (2021) · Viruses · doi:10.3390/v13020213 · Cited by 19
“In addition, the onset of RT in the cytoplasm may be necessary for efficient nuclear import [74].”
BackgroundMaarifi, G., Lagisquet, J., Hertel, Q., Bonaventure, B., Chamontin, C., Fuchs, K. J., Moncorgé, O., Tauziet, M., Mombled, M., Papin, L., et al. (2021) · The EMBO Journal · doi:10.15252/embj.2020106540 · Cited by 16
“Such aspect appears of interest in light of the recent ground-breaking reports of viral uncoating in the nucleus (Dharan et al , 2020; Selyu-tina et al , 2020).”
Teaching old dogmas new tricks: recent insights into the nuclear import of HIV-1
Dharan, A., & Campbell, E. M. (2022) · Current Opinion in Virology · doi:10.1016/j.coviro.2022.101203 · Cited by 20
Self-citationApplications of Atomic Force Microscopy in HIV-1 Research
Rousso, I. Y., & Deshpande, A. (2022) · Viruses · doi:10.3390/v14030648 · Cited by 21
The discovery and design of novel HIV-1 capsid modulators and future perspectives
Ding, D., Xu, S., Zhang, X., Jiang, X., Cocklin, S., Dick, A., Zhan, P., & Liu, X. (2022) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2023.2157401 · Cited by 18
“However, recent studies have shown that intact or partly intact CA cones enter the nucleus through the nuclear pore complex, and complete core disassembly occurs within the nucleus, potentially linking nuclear uncoating events to integration [66].”
BackgroundIngram, Z., Kline, C. E., Hughson, A. K., Singh, P. K., Fischer, H. L., Radhakrishnan, R., Sowd, G. A., dos Santos, N. F. B., Ganser‐Pornillos, B. K., Watkins, S. C., et al. (2025) · mBio · doi:10.1128/mbio.00169-25 · Cited by 16
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Cell-free assays reveal that the HIV-1 capsid protects reverse transcripts from cGAS immune sensing
Scott, T. M., Arnold, L. M., Powers, J. A., McCann, D., Rowe, A. B., Christensen, D. E., Pereira, M. J. B., Zhou, W., Torrez, R. M., Iwasa, J., et al. (2025) · PLoS Pathogens · doi:10.1371/journal.ppat.1012206 · Cited by 16
Insights into HIV uncoating from single-particle imaging techniques
Zhang, M. J., Stear, J. H., Jacques, D. A., & Böcking, T. (2022) · Biophysical Reviews · doi:10.1007/s12551-021-00922-6 · Cited by 16
Getting on the right track: Interactions between viruses and the cytoskeletal motor proteins
Río-Bergé, C., Cong, Y., & Reggiori, F. (2022) · Traffic · doi:10.1111/tra.12835 · Cited by 15
Emerging role of cyclophilin A in HIV-1 infection: from producer cell to the target cell nucleus
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“Distinct, but complementary, nuclear import pathways can coexist and collectively contribute to productiveinfection 32 .”
Role of Type I Interferons during Mycobacterium tuberculosis and HIV Infections
Anes, E., Azevedo‐Pereira, J. M., & Pires, D. (2024) · Biomolecules · doi:10.3390/biom14070848 · Cited by 15
“In fact, the process of descapsidation seems to occur at the nuclear pore or even inside the nucleus of the infected cell [148–152].”
BackgroundA New Generation of Functional Tagged Proteins for HIV Fluorescence Imaging
Mamede, J. I., Griffin, J., Gambut, S., & Hope, T. J. (2021) · Viruses · doi:10.3390/v13030386 · Cited by 13
“Some of these validation methods may include functional, drug add-ins and washouts, biochemical assays, and new approaches that evaluate the kinetics of nuclear import [36].”
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HIV Latency and Nanomedicine Strategies for Anti-HIV Treatment and Eradication
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Antiviral Properties of HIV-1 Capsid Inhibitor GSK878
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HIV Infection: Shaping the Complex, Dynamic, and Interconnected Network of the Cytoskeleton
Cabrera-Rodríguez, R., Pérez-Yanes, S., Lorenzo-Sánchez, I., Trujillo‐González, R., Estévez‐Herrera, J., García-Luis, J., & Valenzuela-Fernández, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241713104 · Cited by 14
HIV-1-induced translocation of CPSF6 to biomolecular condensates
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“Uncoating is thought to be triggered by reverse transcription [5–9], but the site of reverse transcription has also recently been re-evaluated, and it is now thought that reverse transcription completes in the nucleus [10–12].”
BackgroundHIV-1 Hijacking of Host ATPases and GTPases That Control Protein Trafficking
Tavares, L., Januário, Y. C., & daSilva, L. L. P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.622610 · Cited by 12
Ingram, Z., Fischer, D. K., & Ambrose, Z. (2021) · Viruses · doi:10.3390/v13112237 · Cited by 12
“Kinetic analysis has also suggested that the HIV-1 capsid is required until after nuclear import by the HIV-1 nuclear import kinetics (NIK) assay [104].”
BackgroundAdvances in Continuous Microfluidics-Based Technologies for the Study of HIV Infection
Eid, J., Mougel, M., & Socol, M. (2020) · Viruses · doi:10.3390/v12090982 · Cited by 11
“These data fundamentally change our current spatiotemporal vision of these post entry events [26,27].”
BackgroundStrategies for the Viral Exploitation of Nuclear Pore Transport Pathways
Zhang, X., Lim, K., Qiu, Y., Hazawa, M., & Wong, R. W.-C. (2025) · Viruses · doi:10.3390/v17020151 · Cited by 11
“Recent investigations indicate that the HIV-1 capsid remains intact during reverse transcription and may only uncoat upon entering the nucleus [165–168].”
Metadata
- Authors
- Dharan, A., Bachmann, N., Talley, S., Zwikelmaier, V., & Campbell, E. M.
- Affiliations
- Loyola University Chicago (US)
- Corresponding author
- Campbell, Edward M.
- Venue
- Nature Microbiology
- Published
- 2020-06-01
- Volume
- 5
- Issue
- 9
- Pages
- 1088-1095
- ISSN
- 2058-5276 (ISSN-L)
- PMC
- PMC9286700
- OpenAlex
- W3031494023
- Cited by
- 223
- References
- 30
- Citations by year
- 2026: 21 · 2025: 36 · 2024: 40 · 2023: 26 · 2022: 26 · 2021: 53 · 2020: 21
- FWCI
- 16.59
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Microbiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases (R21 AI139009)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Keywords
- HIV-1, reverse transcription, viral uncoating, nuclear import, nuclear pore complex, capsid protein, Nup62, capsid mutants, lentiviral infection
- MeSH terms
- Capsid, Cell Nucleus, Cytoplasm, HeLa Cells, Humans, Indoles, Macrophages, Phenylalanine, Virus Replication, CD4-Positive T-Lymphocytes, HIV-1, HIV Infections, Active Transport, Cell Nucleus, Nuclear Pore, Capsid Proteins, Reverse Transcription, Host-Pathogen Interactions, HEK293 Cells
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