Complementary assays reveal a relationship between HIV-1 uncoating and reverse transcription

Hulme, Amy E.; Perez, Omar; Hope, Thomas J.

doi:10.1073/pnas.1014522108

Cited by 277HIV Research and TreatmentHIV/AIDS drug development and treatmentT-cell and Retrovirus Studies

Complementary assays reveal a relationship between HIV-1 uncoating and reverse transcription

Open access

Hulme, Amy E., Perez, Omar, Hope, Thomas J.·2011·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1014522108PMC PMC3116424

Open this paper in CoChat — free account

Abstract

During the early stages of HIV-1 replication the conical capsid composed of p24 CA protein dissociates from the rest of the cytoplasmic viral complex by a process called uncoating. Although proper uncoating is known to be required for HIV-1 infection, many questions remain about the timing and factors involved in the process. Here we have used two complementary assays to study the process of uncoating in HIV-1–infected cells, specifically looking at the timing of uncoating and its relationship to reverse transcription. We developed a fluorescent microscopy-based uncoating assay that detects the association of p24 CA with HIV-1 viral complexes in cells. We also used an owl monkey kidney (OMK) cell assay that is based on timed TRIM-CypA–mediated restriction of HIV-1 replication. Results from both assays indicate that uncoating is initiated within 1 h of viral fusion. In addition, treatment with the reverse transcriptase inhibitor nevirapine delayed uncoating in both assays. Analysis of reverse transcription products in OMK cells revealed that the generation of early reverse transcription products coincides with the timing of uncoating in these assays. Collectively, these results suggest that some aspect of reverse transcription has the ability to influence the kinetics of uncoating.

Integrity signals

Registry

Crossref · 10.1073/pnas.1014522108

Cites

29 of 29 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

The reverse transcription complex is actively transported to the chromosomal DNA, where integration may occur.
“This RTC is actively transported to the chromosomal DNA, where integration may occur [6–9].”
From Clinical use of lentiviral vectors (2018) · cites this paper as [9]

CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia
He, J., Chen, Y., Farzan, M., Choe, H., Öhagen, Å., Gartner, S., Busciglio, J. A., Yang, X., Hofmann, W., Newman, W., et al. (1997) · Nature · doi:10.1038/385645a0 · Cited by 915 · see citing works
Visualization of the intracellular behavior of HIV in living cells
McDonald, D. J., Vodicka, M. A., Lucero, G. R., Svitkina, T., Borisy, G. G., Emerman, M., & Hope, T. J. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200203150 · Cited by 807 · see citing works
Self-citation
How Viruses Enter Animal Cells
Smith, A. E., & Helenius, A. (2004) · Science · doi:10.1126/science.1094823 · Cited by 735 · see citing works
A quantitative assay for HIV DNA integration in vivo
Butler, S. L., Hansen, M. S., & Bushman, F. D. (2001) · Nature Medicine · doi:10.1038/87979 · Cited by 688 · see citing works
Human Immunodeficiency Virus Type 1 Spinoculation Enhances Infection through Virus Binding
O’Doherty, U., Swiggard, W. J., & Malim, M. H. (2000) · Journal of Virology · doi:10.1128/jvi.74.21.10074-10080.2000 · Cited by 665 · see citing works
Cyclophilin A retrotransposition into TRIM5 explains owl monkey resistance to HIV-1
Sayah, D. M., Sokolskaja, E., Berthoux, L., & Luban, J. (2004) · Nature · doi:10.1038/nature02777 · Cited by 662 · see citing works
Human immunodeficiency virus type 1 preintegration complexes: studies of organization and composition
Miller, M. D., Farnet, C. M., & Bushman, F. D. (1997) · Journal of Virology · doi:10.1128/jvi.71.7.5382-5390.1997 · Cited by 619 · see citing works
Nevirapine resistance mutations of human immunodeficiency virus type 1 selected during therapy
Richman, D. D., Havlir, D. V., Corbeil, J., Looney, D. J., Ignacio, C., Spector, S. A., Sullivan, J., Cheeseman, S. H., Barringer, K., & Pauletti, D. (1994) · Journal of Virology · doi:10.1128/jvi.68.3.1660-1666.1994 · Cited by 576 · see citing works
Formation of a Human Immunodeficiency Virus Type 1 Core of Optimal Stability Is Crucial for Viral Replication
Forshey, B. M., von Schwedler, U. K., Sundquist, W. I., & Aiken, C. (2002) · Journal of Virology · doi:10.1128/jvi.76.11.5667-5677.2002 · Cited by 522 · see citing works
Association of integrase, matrix, and reverse transcriptase antigens of human immunodeficiency virus type 1 with viral nucleic acids following acute infection.
Bukrinsky, M. I., Sharova, N., McDonald, T. L., Pushkarskaya, T., Tarpley, W. G., & Stevenson, M. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.13.6125 · Cited by 451 · see citing works
Functional Surfaces of the Human Immunodeficiency Virus Type 1 Capsid Protein
von Schwedler, U. K., Stray, K. M., Garrus, J. E., & Sundquist, W. I. (2003) · Journal of Virology · doi:10.1128/jvi.77.9.5439-5450.2003 · Cited by 421 · see citing works
Human immunodeficiency virus type 1 mutants resistant to nonnucleoside inhibitors of reverse transcriptase arise in tissue culture.
Richman, D. D., Shih, C. K., Lowy, I., Rose, J., Prodanovich, P., Goff, S. P., & Griffin, J. A. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.24.11241 · Cited by 391 · see citing works
Cyclophilin A modulates the sensitivity of HIV-1 to host restriction factors
Towers, G. J., Hatziioannou, T., Cowan, S., Goff, S. P., Luban, J., & Bieniasz, P. D. (2003) · Nature Medicine · doi:10.1038/nm910 · Cited by 377 · see citing works
Characterization of Intracellular Reverse Transcription Complexes of Human Immunodeficiency Virus Type 1
Fassati, A., & Goff, S. P. (2001) · Journal of Virology · doi:10.1128/jvi.75.8.3626-3635.2001 · Cited by 333 · see citing works
A Trim5-cyclophilin A fusion protein found in owl monkey kidney cells can restrict HIV-1
Nisole, S., Lynch, C., Stoye, J. P., & Yap, M. W. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404640101 · Cited by 304 · see citing works
HIV‐1 DNA Flap formation promotes uncoating of the pre‐integration complex at the nuclear pore
Arhel, N. J., Souquère, S., Munier, S., Souque, P., Guadagnini, S., Rutherford, S. A., Prévost, M., Allen, T. D., & Charneau, P. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601740 · Cited by 295 · see citing works
Proteasome inhibitors uncouple rhesus TRIM5α restriction of HIV-1 reverse transcription and infection
Wu, X., Anderson, J. L., Campbell, E. M., Joseph, A. M., & Hope, T. J. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510483103 · Cited by 265 · see citing works
Self-citation
TRIM5α selectively binds a restriction-sensitive retroviral capsid
Sebastian, S., & Luban, J. (2005) · Retrovirology · doi:10.1186/1742-4690-2-40 · Cited by 240 · see citing works
Inhibition of Endosomal/Lysosomal Degradation Increases the Infectivity of Human Immunodeficiency Virus
Fredericksen, B. L., Wei, B. L., Yao, J. Q., Luo, T., & García, J. V. (2002) · Journal of Virology · doi:10.1128/jvi.76.22.11440-11446.2002 · Cited by 211 · see citing works
Evidence for Direct Involvement of the Capsid Protein in HIV Infection of Nondividing Cells
Yamashita, M., Perez, O., Hope, T. J., & Emerman, M. (2007) · PLoS Pathogens · doi:10.1371/journal.ppat.0030156 · Cited by 200 · see citing works
Self-citation
Evidence for a Functional Link between Uncoating of the Human Immunodeficiency Virus Type 1 Core and Nuclear Import of the Viral Preintegration Complex
Dismuke, D. J., & Aiken, C. (2006) · Journal of Virology · doi:10.1128/jvi.80.8.3712-3720.2006 · Cited by 194 · see citing works
Proteasome Inhibition Reveals that a Functional Preintegration Complex Intermediate Can Be Generated during Restriction by Diverse TRIM5 Proteins
Anderson, J. L., Campbell, E. M., Wu, X., Vandegraaff, N., Engelman, A., & Hope, T. J. (2006) · Journal of Virology · doi:10.1128/jvi.01052-06 · Cited by 173 · see citing works
Self-citation
Restriction of Human Immunodeficiency Virus Type 1 by TRIM-CypA Occurs with Rapid Kinetics and Independently of Cytoplasmic Bodies, Ubiquitin, and Proteasome Activity
Pérez-Caballero, D., Hatziioannou, T., Zhang, F., Cowan, S., & Bieniasz, P. D. (2005) · Journal of Virology · doi:10.1128/jvi.79.24.15567-15572.2005 · Cited by 151 · see citing works
Labeling HIV-1 virions with two fluorescent proteins allows identification of virions that have productively entered the target cell
Campbell, E. M., Perez, O., Melar, M., & Hope, T. J. (2006) · Virology · doi:10.1016/j.virol.2006.10.025 · Cited by 137 · see citing works
Self-citation
Structural Requirements for Recognition of the Human Immunodeficiency Virus Type 1 Core during Host Restriction in Owl Monkey Cells
Forshey, B. M., Shi, J., & Aiken, C. (2004) · Journal of Virology · doi:10.1128/jvi.79.2.869-875.2005 · Cited by 80 · see citing works
Disassembly of Human Immunodeficiency Virus Type 1 Cores In Vitro Reveals Association of Nef with the Subviral Ribonucleoprotein Complex
Forshey, B. M., & Aiken, C. R. (2003) · Journal of Virology · doi:10.1128/jvi.77.7.4409-4414.2003 · Cited by 76 · see citing works
Saturation of TRIM5α-mediated restriction of HIV-1 infection depends on the stability of the incoming viral capsid
Shi, J., & Aiken, C. (2006) · Virology · doi:10.1016/j.virol.2006.03.013 · Cited by 76 · see citing works
Making Membranes Green: Construction and Characterization of GFP-Fusion Proteins Targeted to Discrete Plasma Membrane Domains
Rodgers, W. (2002) · BioTechniques · doi:10.2144/02325st05 · Cited by 60 · see citing works
Natural Endogenous Reverse Transcription of HIV Type 1
Zhang, H., Dornadula, G., & Pomerantz, R. J. (1998) · AIDS Research and Human Retroviruses · doi:10.1177/088922299801401s20 · Cited by 14 · see citing works

Flagged first, then by citations

Sorted by citations

Clinical use of lentiviral vectors
Milone, M. C., & O’Doherty, U. (2018) · Leukemia · doi:10.1038/s41375-018-0106-0 · Cited by 930 · see citing works
HIV-1 assembly, release and maturation
Freed, E. O. (2015) · Nature Reviews Microbiology · doi:10.1038/nrmicro3490 · Cited by 654 · see citing works
HIV-1 capsid: the multifaceted key player in HIV-1 infection
Campbell, E. M., & Hope, T. J. (2015) · Nature Reviews Microbiology · doi:10.1038/nrmicro3503 · Cited by 430 · see citing works
Self-citation
HIV-1 uncoats in the nucleus near sites of integration
Burdick, R. C., Li, C., Munshi, M., Rawson, J. M. O., Nagashima, K., Hu, W.-S., & Pathak, V. K. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1920631117 · Cited by 313 · see citing works
Host Cofactors and Pharmacologic Ligands Share an Essential Interface in HIV-1 Capsid That Is Lost upon Disassembly
Price, A. J., Jacques, D. A., McEwan, W. A., Fletcher, A. J., Essig, S., Chin, J. W., Halambage, U. D., Aiken, C., & James, L. C. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1004459 · Cited by 284 · see citing works
Nucleoporin NUP153 Phenylalanine-Glycine Motifs Engage a Common Binding Pocket within the HIV-1 Capsid Protein to Mediate Lentiviral Infectivity
Matreyek, K. A., Yücel, S. S., Li, X., & Engelman, A. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003693 · Cited by 280 · see citing works
CPSF6 Defines a Conserved Capsid Interface that Modulates HIV-1 Replication
Price, A., Fletcher, A. J., Schaller, T., Elliott, T., Lee, K., KewalRamani, V., Chin, J., Towers, G., & James, L. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002896 · Cited by 276 · see citing works
Nuclear pore blockade reveals that HIV-1 completes reverse transcription and uncoating in the nucleus
Dharan, A., Bachmann, N., Talley, S., Zwikelmaier, V., & Campbell, E. M. (2020) · Nature Microbiology · doi:10.1038/s41564-020-0735-8 · Cited by 223 · see citing works
Restriction of HIV-1 and other retroviruses by TRIM5
Ganser-Pornillos, B. K., & Pornillos, O. (2019) · Nature Reviews Microbiology · doi:10.1038/s41579-019-0225-2 · Cited by 163 · see citing works
Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport
Francis, A. C., & Melikyan, G. B. (2018) · Cell Host & Microbe · doi:10.1016/j.chom.2018.03.009 · Cited by 176 · see citing works
HIV-1 Uncoating: Connection to Nuclear Entry and Regulation by Host Proteins
Ambrose, Z., & Aiken, C. (2014) · Virology · doi:10.1016/j.virol.2014.02.004 · Cited by 180 · see citing works
Quantitative microscopy of functional HIV post-entry complexes reveals association of replication with the viral capsid
Peng, K., Muranyi, W., Glass, B., Laketa, V., Yant, S. R., Tsai, L. K., Cihlář, T., Müller, B., & Kräusslich, H. (2014) · eLife · doi:10.7554/elife.04114 · Cited by 158 · see citing works
Superresolution imaging of HIV in infected cells with FlAsH-PALM
Lelek, M., Nunzio, F. D., Henriques, R., Charneau, P., Arhel, N. J., & Zimmer, C. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1013267109 · Cited by 156 · see citing works
Nuclear import of the HIV-1 core precedes reverse transcription and uncoating
Selyutina, A., Persaud, M., Lee, K., KewalRamani, V., & Diaz-Griffero, F. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108201 · Cited by 144 · see citing works
Viral and Cellular Requirements for the Nuclear Entry of Retroviral Preintegration Nucleoprotein Complexes
Matreyek, K. A., & Engelman, A. (2013) · Viruses · doi:10.3390/v5102483 · Cited by 142 · see citing works
TNPO3 protects HIV-1 replication from CPSF6-mediated capsid stabilization in the host cell cytoplasm
Iaco, A. D., Santoni, F. A., Vannier, A., Guipponi, M., Antonarakis, S. E., & Luban, J. (2013) · Retrovirology · doi:10.1186/1742-4690-10-20 · Cited by 140 · see citing works
Early cytoplasmic uncoating is associated with infectivity of HIV-1
Mamede, J., Cianci, G. C., Anderson, M. R., & Hope, T. (2017) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1706245114 · Cited by 128 · see citing works
Self-citation
HIV-1 Induces the Formation of Stable Microtubules to Enhance Early Infection
Sabo, Y., Walsh, D., Barry, D., Tinaztepe, S., Santos, K. D. L., Goff, S. P., Gundersen, G. G., & Naghavi, M. H. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.10.012 · Cited by 137 · see citing works
Reverse transcription mechanically initiates HIV-1 capsid disassembly
Rankovic, S., Varadarajan, J., Ramalho, R., Aiken, C., & Rousso, I. (2017) · Journal of Virology · doi:10.1128/jvi.00289-17 · Cited by 130 · see citing works
Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration
Zhou, L., Sokolskaja, E., Jolly, C., James, W., Cowley, S. A., & Fassati, A. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002194 · Cited by 130 · see citing works
HIV-1 Uncoating Is Facilitated by Dynein and Kinesin 1
Lukic, Z., Dharan, A., Fricke, T., Diaz‐Griffero, F., & Campbell, E. M. (2014) · Journal of Virology · doi:10.1128/jvi.02219-14 · Cited by 130 · see citing works
The Host Proteins Transportin SR2/TNPO3 and Cyclophilin A Exert Opposing Effects on HIV-1 Uncoating
Shah, V. B., Shi, J., Hout, D., Oztop, I., Krishnan, L., Ahn, J., Shotwell, M., Engelman, A., & Aiken, C. (2012) · Journal of Virology · doi:10.1128/jvi.07177-11 · Cited by 133 · see citing works
Differential Effects of Human Immunodeficiency Virus Type 1 Capsid and Cellular Factors Nucleoporin 153 and LEDGF/p75 on the Efficiency and Specificity of Viral DNA Integration
Koh, Y., Wu, X., Ferris, A. L., Matreyek, K. A., Smith, S. J., Lee, K., KewalRamani, V. N., Hughes, S. H., & Engelman, A. (2013) · Journal of Virology · doi:10.1128/jvi.01148-12 · Cited by 122 · see citing works
HIV-1 uncoating by release of viral cDNA from capsid-like structures in the nucleus of infected cells
Müller, 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 117 · see citing works
Capsid-Dependent Host Factors in HIV-1 Infection
Yamashita, M., & Engelman, A. (2017) · Trends in Microbiology · doi:10.1016/j.tim.2017.04.004 · Cited by 123 · see citing works
Time-Resolved Imaging of Single HIV-1 Uncoating In Vitro and in Living Cells
Francis, A. C., Marin, M., Shi, J., Aiken, C., & Melikyan, G. B. (2016) · PLoS Pathogens · doi:10.1371/journal.ppat.1005709 · Cited by 119 · see citing works
Ebselen, a Small-Molecule Capsid Inhibitor of HIV-1 Replication
Thenin-Houssier, S., de Vera, I. M. S., Pedró-Rosa, L., Brady, A., Richard, A. S., Konnick, B., Opp, S., Buffone, C., Fuhrmann, J., Kota, S., et al. (2016) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02574-15 · Cited by 114 · see citing works
HIV-1 capsid undergoes coupled binding and isomerization by the nuclear pore protein NUP358
Bichel, K., Price, A., Schaller, T., Towers, G., Freund, S., & James, L. (2013) · Retrovirology · doi:10.1186/1742-4690-10-81 · Cited by 116 · see citing works
Inhibitors of the HIV-1 capsid, a target of opportunity
Carnes, S. K., Sheehan, J. H., & Aiken, C. (2018) · Current Opinion in HIV and AIDS · doi:10.1097/coh.0000000000000472 · Cited by 113 · see citing works
Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA
Iaco, A. D., & Luban, J. (2014) · Retrovirology · doi:10.1186/1742-4690-11-11 · Cited by 111 · see citing works
Kinetics of HIV-1 capsid uncoating revealed by single-molecule analysis
Márquez, C. L., Lau, D., Walsh, J. C., Shah, V. B., McGuinness, C., Wong, A. K. H., Aggarwal, A., Parker, M. W., Jacques, D. A., Turville, S. G., et al. (2018) · eLife · doi:10.7554/elife.34772 · Cited by 111 · see citing works
The activity of Nef on HIV-1 infectivity
Basmaciogullari, S., & Pizzato, M. (2014) · Frontiers in Microbiology · doi:10.3389/fmicb.2014.00232 · Cited by 110 · see citing works
Complementary Assays Reveal a Low Level of CA Associated with Viral Complexes in the Nuclei of HIV-1-Infected Cells
Hulme, A. E., Kelley, Z. L., Foley, D., & Hope, T. J. (2015) · Journal of Virology · doi:10.1128/jvi.00476-15 · Cited by 105 · see citing works
Self-citation
Multiple roles of the capsid protein in the early steps of HIV-1 infection
Fassati, A. (2012) · Virus Research · doi:10.1016/j.virusres.2012.09.012 · Cited by 100 · see citing works
Inhibition of Reverse Transcriptase Activity Increases Stability of the HIV-1 Core
Yang, Y., Fricke, T., & Diaz‐Griffero, F. (2012) · Journal of Virology · doi:10.1128/jvi.01228-12 · Cited by 99 · see citing works
Multiple Roles of HIV-1 Capsid during the Virus Replication Cycle
Novikova, M., Zhang, Y., Freed, E. O., & Peng, K. (2019) · Virologica Sinica · doi:10.1007/s12250-019-00095-3 · Cited by 95 · see citing works
Nuclear 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 94 · see citing works
Human Immunodeficiency Virus Type 1 Capsid Mutation N74D Alters Cyclophilin A Dependence and Impairs Macrophage Infection
Ambrose, Z., Lee, K., Ndjomou, J., Xu, H.-Z., Oztop, I., Matous, J., Takemura, T., Unutmaz, D., Engelman, A., Hughes, S., et al. (2012) · Journal of Virology · doi:10.1128/jvi.05887-11 · Cited by 96 · see citing works
Direct Visualization of HIV-1 with Correlative Live-Cell Microscopy and Cryo-Electron Tomography
Jun, S., Ke, D., Debiec, K. T., Zhao, G., Meng, X., Ambrose, Z., Gibson, G. A., Watkins, S. C., & Zhang, P. (2011) · Structure · doi:10.1016/j.str.2011.09.006 · Cited by 93 · see citing works
Inhibition of HIV-1 infection by TNPO3 depletion is determined by capsid and detectable after viral cDNA enters the nucleus
Iaco, A. D., & Luban, J. (2011) · Retrovirology · doi:10.1186/1742-4690-8-98 · Cited by 92 · see citing works
Murine leukemia virus glycosylated Gag blocks apolipoprotein B editing complex 3 and cytosolic sensor access to the reverse transcription complex
Stavrou, S., Nitta, T., Kotla, S., Ha, D. P., Nagashima, K., Rein, A. R., Fan, H., & Ross, S. R. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1217399110 · Cited by 91 · see citing works
Fates of Retroviral Core Components during Unrestricted and TRIM5-Restricted Infection
Kutluay, S. B., Pérez-Caballero, D., & Bieniasz, P. D. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003214 · Cited by 92 · see citing works
A model for cofactor use during HIV-1 reverse transcription and nuclear entry
Hilditch, L., & Towers, G. (2014) · Current Opinion in Virology · doi:10.1016/j.coviro.2013.11.003 · Cited by 96 · see citing works
HIV-1 capsid uncoating initiates after the first strand transfer of reverse transcription
Cosnefroy, O., Murray, P. J., & Bishop, K. N. (2016) · Retrovirology · doi:10.1186/s12977-016-0292-7 · Cited by 91 · see citing works
Maturation-Associated Destabilization of Hepatitis B Virus Nucleocapsid
Cui, X., Ludgate, L., Ning, X., & Hu, J. (2013) · Journal of Virology · doi:10.1128/jvi.01912-13 · Cited by 90 · see citing works
Remodeling of the Core Leads HIV-1 Preintegration Complex into the Nucleus of Human Lymphocytes
Blanco-Rodriguez, G., Gazi, A. D., Monel, B., Frabetti, S., Scoca, V., Mueller, F., Schwartz, O., Krijnse‐Locker, J., Charneau, P., & Nunzio, F. D. (2020) · Journal of Virology · doi:10.1128/jvi.00135-20 · Cited by 89 · see citing works
Roles of Capsid-Interacting Host Factors in Multimodal Inhibition of HIV-1 by PF74
Saito, A., Ferhadian, D., Sowd, G. A., Serrao, E., Shi, J., Halambage, U. D., Teng, S., Soto, J., Siddiqui, M. A., Engelman, A., et al. (2016) · Journal of Virology · doi:10.1128/jvi.03116-15 · Cited by 85 · see citing works
Mechanisms and Factors that Influence High Frequency Retroviral Recombination
Delviks‐Frankenberry, K. A., Galli, A., Nikolaitchik, O. A., Mens, H., Pathak, V. K., & Hu, W.-S. (2011) · Viruses · doi:10.3390/v3091650 · Cited by 87 · see citing works
Evidence for biphasic uncoating during HIV-1 infection from a novel imaging assay
Xu, H., Franks, T., Gibson, G. A., Huber, K. D., Rahm, N., Strambio‐De‐Castillia, C., Luban, J., Aiken, C., Watkins, S. C., Sluis‐Cremer, N., et al. (2013) · Retrovirology · doi:10.1186/1742-4690-10-70 · Cited by 83 · see citing works
HIV-1 capsid inhibitors as antiretroviral agents
Thenin-Houssier, S., & Valente, S. (2016) · Current HIV Research · doi:10.2174/1570162x14999160224103555 · Cited by 75 · see citing works
Microtubule-associated Proteins 1 (MAP1) Promote Human Immunodeficiency Virus Type I (HIV-1) Intracytoplasmic Routing to the Nucleus
Fernandez, J., Portilho, D., Danckaert, A., Munier, S., Becker, A., Roux, P., Zambo, A., Shorte, S., Jacob, Y., Vidalain, P.-O., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.613133 · Cited by 71 · see citing works
HIV Type 1 Gag as a Target for Antiviral Therapy
Waheed, A. A., & Freed, E. O. (2011) · AIDS Research and Human Retroviruses · doi:10.1089/aid.2011.0230 · Cited by 81 · see citing works
PF74 Reinforces the HIV-1 Capsid To Impair Reverse Transcription-Induced Uncoating
Rankovic, S., Ramalho, R., Aiken, C., & Rousso, I. (2018) · Journal of Virology · doi:10.1128/jvi.00845-18 · Cited by 68 · see citing works
Mechanisms of Virologic Control and Clinical Characteristics of HIV+ Elite/Viremic Controllers.
Gonzalo-Gil, E., Ikediobi, U., & Sutton, R. E. (2017) · Europe PMC (PubMed Central) · Cited by 79 · see citing works
Virus-producing cells determine the host protein profiles of HIV-1 virion cores
Santos, S., Obukhov, Y., Nekhai, S. A., Bukrinsky, M., & Iordanskiy, S. (2012) · Retrovirology · doi:10.1186/1742-4690-9-65 · Cited by 78 · see citing works
Nanoparticle-based flow virometry for the analysis of individual virions
Arakelyan, A., Fitzgerald, W., Margolis, L. B., & Grivel, J. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67042 · Cited by 79 · see citing works
Virus-inspired nucleic acid delivery system: Linking virus and viral mimicry
Ni, R., Zhou, J., Hossain, N., & Chau, Y. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2016.07.005 · Cited by 78 · see citing works
Inhibiting Early-Stage Events in HIV-1 Replication by Small-Molecule Targeting of the HIV-1 Capsid
Kortagere, S., Madani, N., Mankowski, M. K., Schön, A., Zentner, I., Swaminathan, G., Princiotto, A. M., Anthony, K., Oza, A., Sierra, L., et al. (2012) · Journal of Virology · doi:10.1128/jvi.05006-11 · Cited by 77 · see citing works
Nuclear import of APOBEC3F-labeled HIV-1 preintegration complexes
Burdick, R. C., Hu, W.-S., & Pathak, V. K. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1315996110 · Cited by 76 · see citing works
Reverse Transcription of Retroviruses and LTR Retrotransposons
Hughes, S. H. (2015) · Microbiology Spectrum · doi:10.1128/microbiolspec.mdna3-0027-2014 · Cited by 73 · see citing works
Identification of Capsid Mutations That Alter the Rate of HIV-1 Uncoating in Infected Cells
Hulme, A. E., Kelley, Z. L., Okocha, E. A., & Hope, T. J. (2014) · Journal of Virology · doi:10.1128/jvi.03043-14 · Cited by 71 · see citing works
Self-citation
IP6 Regulation of HIV Capsid Assembly, Stability, and Uncoating
Dick, R. A., Mallery, D. L., Vogt, V. M., & James, L. C. (2018) · Viruses · doi:10.3390/v10110640 · Cited by 71 · see citing works
HIV-1 capsid is involved in post-nuclear entry steps
Chen, N., Zhou, L., Gane, P., Opp, S., Ball, N., Nicastro, G., Zufferey, M., Buffone, C., Luban, J., Selwood, D. L., et al. (2016) · Retrovirology · doi:10.1186/s12977-016-0262-0 · Cited by 62 · see citing works
Rotten to the core: antivirals targeting the HIV-1 capsid core
McFadden, W. M., Snyder, A. A., Kirby, K. A., Tedbury, P. R., Raj, M., Wang, Z., & Sarafianos, S. G. (2021) · Retrovirology · doi:10.1186/s12977-021-00583-z · Cited by 65 · see citing works
Eukaryotic elongation factor 1 complex subunits are critical HIV-1 reverse transcription cofactors
Warren, K., Wei, T., Li, D., Fangyun, Q., Warrilow, D., Lin, M., Sivakumaran, H., Apolloni, A., Abbott, C. M., Jones, A., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1204673109 · Cited by 66 · see citing works
Discovery of phenylalanine derivatives as potent HIV-1 capsid inhibitors from click chemistry-based compound library
Wu, G., Zalloum, W. A., Meuser, M. E., Jing, L., Kang, D., Chen, C., Tian, Y., Zhang, F., Cocklin, S., Lee, K., et al. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.09.029 · Cited by 66 · see citing works
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 65 · see citing works
The cleavage and polyadenylation specificity factor 6 (CPSF6) subunit of the capsid-recruited pre-messenger RNA cleavage factor I (CFIm) complex mediates HIV-1 integration into genes
Rasheedi, S., Shun, M.-C., Serrao, E., Sowd, G. A., Qian, J., Hao, C., Dasgupta, T., Engelman, A. N., & Skowronski, J. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.721647 · Cited by 65 · see citing works
APOBEC3 Inhibition of Mouse Mammary Tumor Virus Infection: the Role of Cytidine Deamination versus Inhibition of Reverse Transcription
MacMillan, A. L., Kohli, R. M., & Ross, S. R. (2013) · Journal of Virology · doi:10.1128/jvi.00112-13 · Cited by 64 · see citing works
Molecular Studies of HTLV-1 Replication: An Update
Martin, J., Maldonado, J. O., Mueller, J. D., Zhang, W., & Mansky, L. M. (2016) · Viruses · doi:10.3390/v8020031 · Cited by 66 · see citing works
In vitro methods for testing antiviral drugs
Rumlová, M., & Ruml, T. (2017) · Biotechnology Advances · doi:10.1016/j.biotechadv.2017.12.016 · Cited by 62 · see citing works
Interaction of the HIV-1 Intasome with Transportin 3 Protein (TNPO3 or TRN-SR2)
Larue, R. C., Gupta, K., Wuensch, C., Shkriabai, N., Kessl, J. J., Danhart, E., Feng, L., Taltynov, O., Christ, F., Duyne, G. D. V., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.384669 · Cited by 58 · see citing works
Second-site suppressors of HIV-1 capsid mutations: restoration of intracellular activities without correction of intrinsic capsid stability defects
Yang, R., Shi, J., Byeon, I. L., Ahn, J., Sheehan, J. H., Meiler, J., Gronenborn, A. M., & Aiken, C. (2012) · Retrovirology · doi:10.1186/1742-4690-9-30 · Cited by 59 · see citing works
HIV capsid and integration targeting
Engelman, A. N. (2021) · Viruses · doi:10.3390/v13010125 · Cited by 57 · see citing works
The HIV-1 capsid and reverse transcription
Aiken, C., & Rousso, I. Y. (2021) · Retrovirology · doi:10.1186/s12977-021-00566-0 · Cited by 56 · see citing works
Roles of HIV-1 capsid in viral replication and immune evasion
Sage, V. L., Mouland, A. J., & Valiente‐Echeverría, F. (2014) · Virus Research · doi:10.1016/j.virusres.2014.07.010 · Cited by 56 · see citing works
Human Cytosolic Extracts Stabilize the HIV-1 Core
Fricke, T., Brandariz-Núñez, A., Wang, X., Smith, A. B., & Diaz‐Griffero, F. (2013) · Journal of Virology · doi:10.1128/jvi.01705-13 · Cited by 56 · see citing works
Cytoplasmic Dynein Promotes HIV-1 Uncoating
Pawlica, P., & Berthoux, L. (2014) · Viruses · doi:10.3390/v6114195 · Cited by 56 · see citing works
The NTD-CTD intersubunit interface plays a critical role in assembly and stabilization of the HIV-1 capsid
Yufenyuy, E. L., & Aiken, C. (2013) · Retrovirology · doi:10.1186/1742-4690-10-29 · Cited by 54 · see citing works
HIV-1 Uncoating and Nuclear Import Precede the Completion of Reverse Transcription in Cell Lines and in Primary Macrophages
Francis, A. C., Marin, M., Prellberg, M., Palermino-Rowland, K., & Melikyan, G. B. (2020) · Viruses · doi:10.3390/v12111234 · Cited by 51 · see citing works
The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability
Jiang, J., Ablan, S. D., Derebail, S. S., Hercík, K., Soheilian, F., Thomas, J. A., Tang, S., HEWLETT, I. K., Nagashima, K., Gorelick, R. J., et al. (2011) · Virology · doi:10.1016/j.virol.2011.09.012 · Cited by 52 · see citing works
Multiplex single-cell visualization of nucleic acids and protein during HIV infection
Puray‐Chavez, M., Tedbury, P. R., Huber, A. D., Ukah, O. B., Yapo, V., Liu, D., Ji, J., Wolf, J. J., Engelman, A., & Sarafianos, S. G. (2017) · Nature Communications · doi:10.1038/s41467-017-01693-z · Cited by 52 · see citing works
A 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 52 · see citing works
Analysis of the mechanical properties of wild type and hyperstable mutants of the HIV-1 capsid
Ramalho, R., Rankovic, S., Zhou, J., Aiken, C., & Rousso, I. Y. (2016) · Retrovirology · doi:10.1186/s12977-016-0250-4 · Cited by 50 · see citing works
Distinct functions of diaphanous-related formins regulate HIV-1 uncoating and transport
Delaney, M. K., Malikov, V., Chai, Q., Zhao, G., & Naghavi, M. H. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1700247114 · Cited by 49 · see citing works
The Fate of HIV-1 Capsid: A Biochemical Assay for HIV-1 Uncoating
Yang, Y., Luban, J., & Diaz‐Griffero, F. (2013) · Methods in molecular biology · doi:10.1007/978-1-62703-670-2_3 · Cited by 50 · see citing works
Nuclear Import of HIV-1
Shen, Q., Wu, C., Freniere, C., Tripler, T. N., & Xiong, Y. (2021) · Viruses · doi:10.3390/v13112242 · Cited by 50 · see citing works
Localized Phosphorylation of a Kinesin-1 Adaptor by a Capsid-Associated Kinase Regulates HIV-1 Motility and Uncoating
Malikov, V., & Naghavi, M. H. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.08.076 · Cited by 48 · see citing works
Post-translational Modification-Based Regulation of HIV Replication
Chen, L., Keppler, O. T., & Scholz, C. W. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.02131 · Cited by 46 · see citing works
Off-Pathway Assembly: A Broad-Spectrum Mechanism of Action for Drugs That Undermine Controlled HIV-1 Viral Capsid Formation
Pak, A. J., Grime, J. M. A., Yu, A., & Voth, G. A. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.9b01413 · Cited by 48 · see citing works
HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration
Guedán, A., Donaldson, C. D., Caroe, E. R., Cosnefroy, O., Taylor, I., & Bishop, K. N. (2021) · bioRxiv · doi:10.1371/journal.ppat.1009484 · Cited by 47 · see citing works
Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon-Induced Antiviral Factors
Bulli, L., Apolonia, L., Kutzner, J., Pollpeter, D., Goujon, C., Herold, N., Schwarz, S.-M., Giernat, Y., Keppler, O. T., Malim, M. H., et al. (2016) · Journal of Virology · doi:10.1128/jvi.00458-16 · Cited by 42 · see citing works
Recognition of HIV-1 capsid by PQBP1 licenses an innate immune sensing of nascent HIV-1 DNA
Yoh, S. M., Mamede, J. I., Lau, D., Ahn, N., Sánchez-Aparicio, M. T., Temple, J. E., Tuckwell, A., Fuchs, N. V., Cianci, G. C., Riva, L., et al. (2022) · Molecular Cell · doi:10.1016/j.molcel.2022.06.010 · Cited by 46 · see citing works
Self-citation
Imaging HIV-1 Genomic DNA from Entry through Productive Infection
Stultz, R. D., Cenker, J. J., & McDonald, D. J. (2017) · Journal of Virology · doi:10.1128/jvi.00034-17 · Cited by 46 · see citing works
A Novel Phenotype Links HIV-1 Capsid Stability to cGAS-Mediated DNA Sensing
Siddiqui, M. A., Saito, A., Halambage, U. D., Ferhadian, D., Fischer, D. K., Francis, A. C., Melikyan, G. B., Ambrose, Z., Aiken, C., & Yamashita, M. (2019) · Journal of Virology · doi:10.1128/jvi.00706-19 · Cited by 45 · see citing works
HIV-1 Uncoating Occurs via a Series of Rapid Biomechanical Changes in the Core Related to Individual Stages of Reverse Transcription
Rankovic, S., Deshpande, A., Harel, S., Aiken, C., & Rousso, I. Y. (2021) · Journal of Virology · doi:10.1128/jvi.00166-21 · Cited by 45 · see citing works
Capsid-Labelled HIV To Investigate the Role of Capsid during Nuclear Import and Integration
Zurnic, I., Dirix, L., Lemmens, V., Borrenberghs, D., Wit, F. D., Vernaillen, F., Rocha, S., Christ, F., Hendrix, J., Hofkens, J., et al. (2020) · Journal of Virology · doi:10.1128/jvi.01024-19 · Cited by 44 · see citing works
The 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 · see citing works
An HIV-1 capsid binding protein TRIM11 accelerates viral uncoating
Yuan, T., Yao, W., Tokunaga, K., Yang, R., & Sun, B. (2016) · Retrovirology · doi:10.1186/s12977-016-0306-5 · Cited by 42 · see citing works
HIV-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 41 · see citing works

HIV-1 capsid uncoating initiates after the first strand transfer of reverse transcription
Cosnefroy, O., Murray, P. J., & Bishop, K. N. (2016) · Retrovirology · doi:10.1186/s12977-016-0292-7 · Cited by 91 · see citing works
The Cyclosporin A Washout Assay to Detect HIV-1 Uncoating in Infected Cells
Hulme, A. E., & Hope, T. J. (2013) · Methods in molecular biology · doi:10.1007/978-1-62703-670-2_4 · Cited by 25 · see citing works
Self-citation
Single-Particle Tracking Reveals the Interplay between HIV-1 Reverse Transcription and Uncoating
Ma, Y., Mao, G., Wu, G., & Zhang, X. (2022) · Analytical Chemistry · doi:10.1021/acs.analchem.1c05199 · Cited by 5 · see citing works
Identification of Capsid Mutations That Alter the Rate of HIV-1 Uncoating in Infected Cells
Hulme, A. E., Kelley, Z. L., Okocha, E. A., & Hope, T. J. (2014) · Journal of Virology · doi:10.1128/jvi.03043-14 · Cited by 71 · see citing works
Self-citation
Revisiting HIV-1 uncoating
Arhel, N. (2010) · Retrovirology · doi:10.1186/1742-4690-7-96 · Cited by 200 · see citing works

Authors: Hulme, A. E., Perez, O., & Hope, T. J.
Affiliations: Northwestern University (US)
University of Illinois Chicago (US)
ORCID: Hulme, Amy E.
Perez, Omar
Hope, Thomas J.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2011-05-31
Volume: 108
Issue: 24
Pages: 9975-9980
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.1014522108
PMC: PMC3116424
OpenAlex: W2120792521
Cited by: 276
References: 29
Citations by year: 2026: 6 · 2025: 8 · 2024: 14 · 2023: 9 · 2022: 18 · 2021: 24 · 2020: 24 · 2019: 20 · 2018: 23 · 2017: 15 · 2016: 19 · 2015: 15 · 2014: 24 · 2013: 27 · 2012: 22
FWCI: 10.25
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
BearWorks (Missouri State University) (submittedVersion)
Funders: National Institute of General Medical Sciences (P50GM082545)
National Institute of Allergy and Infectious Diseases (R01-AI47770, R01AI047770)
Topics: Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
Keywords: reverse transcription, viral capsid, viral fusion, nevirapine
MeSH terms: Animals, Cell Line, HeLa Cells, Humans, Luminescent Proteins, Microscopy, Fluorescence, Recombinant Fusion Proteins, Time Factors, Virion, Virus Replication, HIV-1, Cyclosporine, HIV Core Protein p24, Macrolides, Anti-HIV Agents, Nevirapine, Reverse Transcription, Green Fluorescent Proteins, Human Immunodeficiency Virus Proteins, vpr Gene Products, Human Immunodeficiency Virus, HEK293 Cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Complementary assays reveal a relationship between HIV-1 uncoating and reverse transcription

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks