Murine leukemia virus infection of non-dividing dendritic cells is dependent on nucleoporins
Open accessAbstract
Retroviral reverse transcription starts within the capsid and uncoating and reverse transcription are mutually dependent. There is still debate regarding the timing and cellular location of HIV’s uncoating and reverse transcription and whether it occurs solely in the cytoplasm, nucleus or both. HIV can infect non-dividing cells because there is active transport of the preintegration complex (PIC) across the nuclear membrane, but Murine Leukemia Virus (MLV) is thought to depend on cell division for replication and whether MLV uncoating and reverse transcription is solely cytoplasmic has not been studied. Here, we used NIH3T3 and primary mouse dendritic cells to determine where the different stages of reverse transcription occur and whether cell division is needed for nuclear entry. Our data strongly suggest that in both NIH3T3 cells and dendritic cells (DCs), the initial step of reverse transcription occurs in the cytoplasm. However, we detected MLV RNA/DNA hybrid intermediates in the nucleus of dividing NIH3T3 cells and non-dividing DCs, suggesting that reverse transcription can continue after nuclear entry. We also confirmed that the MLV PIC requires cell division to enter the nucleus of NIH3T3 cells. In contrast, we show that MLV can infect non-dividing primary DCs, although integration of MLV DNA in DCs still required the viral p12 protein. Knockdown of several nuclear pore proteins dramatically reduced the appearance of integrated MLV DNA in DCs but not NIH3T3 cells. Additionally, MLV capsid associated with the nuclear pore proteins NUP358 and NUP62 during infection. These findings suggest that simple retroviruses, like the complex retrovirus HIV, gain nuclear entry by traversing the nuclear pore complex in non-mitotic cells.
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MLV initiates reverse transcription in the cytoplasm and completes it within the nucleus in both dividing and nondividing cells.
“A recent study using different cell lines has shown that, similar to HIV-1, MLV initiates reverse transcription in the cytoplasm and completes it within the nucleus in both dividing and nondividing cells.”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Salas-Briceno et al. 2024
The Abstract says the initial step of MLV reverse transcription occurs in the cytoplasm in NIH3T3 cells and dendritic cells, and that nuclear intermediates suggest it can continue after entry. The Discussion says it can be completed in the nucleus in dividing NIH3T3 cells, but the cited passages do not establish nuclear completion in nondividing cells as the claim states. (LLM, conf=0.86)
Experimental — accuracy not yet measuredMLV interacts with nuclear pore complex proteins NUP358 and NUP62 to enter the nucleus in nondividing cells.
“During this process, MLV interacts with NPC proteins NUP358 and NUP62 to enter the nucleus in nondividing cells (Salas-Briceno et al. 2024).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Salas-Briceno et al. 2024
The Results (‘MLV infection of DCs relies on nucleoporins’) show that MLV capsid co-localizes with NUP358 and NUP62 in nondividing dendritic cells, and that nucleoporin knockdown reduces infection in those cells. The Abstract says these findings suggest entry through the nuclear pore complex, but the Discussion says the experiments could not establish which nucleoporin is critical. The claim therefore states the role of those specific interactions in nuclear entry more definitively than the paper does. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn the simple retrovirus MLV, the viral CA can gain access to the nucleus.
“even in the case of a simple retrovirus such as MLV, it has recently been shown that the viral CA can gain access to the nucleus (Salas-Briceno et al. 2024)”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Salas-Briceno et al. 2024
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Cites
Cyclic GMP-AMP Synthase Is an Innate Immune Sensor of HIV and Other Retroviruses
Gao, D., Wu, J., Wu, Y.-T., Du, F., Aroh, C., Yan, N., Sun, L., & Chen, Z. J. (2013) · Science · doi:10.1126/science.1240933 · Cited by 986 · see citing works
Integration of murine leukemia virus DNA depends on mitosis.
Roe, T., Reynolds, T. C., Yu, G., & Brown, P. O. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb05858.x · Cited by 921 · see citing works
Yan, N., Regalado-Magdos, A. D., Stiggelbout, B., Lee‐Kirsch, M. A., & Lieberman, J. (2010) · Nature Immunology · doi:10.1038/ni.1941 · Cited by 522 · see citing works
REAP: A two minute cell fractionation method
Suzuki, K., Bose, P., Leong-Quong, R. Y. Y., Fujita, D. J., & Riabowol, K. T. (2010) · BMC Research Notes · doi:10.1186/1756-0500-3-294 · Cited by 474 · see citing works
The Structure of the Nuclear Pore Complex (An Update)
Lin, D. H., & Hoelz, A. (2019) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-062917-011901 · Cited by 449 · see citing works
Retrotransposons, Endogenous Retroviruses, and the Evolution of Retroelements
Boeke, J. D., & Stoye, J. (1997) · Europe PMC (PubMed Central) · Cited by 444 · see citing works
Lahaye, X., Satoh, T., Gentili, M., Cerboni, S., Conrad, C., Hurbain, I., El Marjou, A., Lacabaratz, C., Lelièvre, J.-D., & Manel, N. (2013) · Immunity · doi:10.1016/j.immuni.2013.11.002 · Cited by 390 · see citing works
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 333 · see citing works
Complementary assays reveal a relationship between HIV-1 uncoating and reverse transcription
Hulme, A. E., Perez, O., & Hope, T. J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1014522108 · Cited by 276 · see citing works
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
BET proteins promote efficient murine leukemia virus integration at transcription start sites
Sharma, A., Larue, R. C., Plumb, M. R., Malani, N., Male, F., Slaughter, A., Kessl, J. J., Shkriabai, N., Coward, E., Aiyer, S. S., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1307157110 · Cited by 193 · see citing works
APOBEC3 inhibits mouse mammary tumour virus replication in vivo
Okeoma, C. M., Lovšin, N., Peterlin, B. M., & Ross, S. R. (2007) · Nature · doi:10.1038/nature05540 · Cited by 186 · see citing works
Self-citationFrancis, A. C., Marin, M., Singh, P. K., Achuthan, V., Prellberg, M. J., Palermino-Rowland, K., Lan, S., Tedbury, P. R., Sarafianos, S. G., Engelman, A. N., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17256-8 · Cited by 159 · see citing works
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 157 · see citing works
Detecting HIV-1 integration by repetitive-sampling -gag PCR
Liszewski, M. K., Yu, J. J., & O’Doherty, U. (2009) · Methods · doi:10.1016/j.ymeth.2009.01.002 · Cited by 157 · see citing works
Reconstitution and visualization of HIV-1 capsid-dependent replication and integration in vitro
Christensen, D. E., Ganser-Pornillos, B. K., Johnson, J. S., Pornillos, O., & Sundquist, W. I. (2020) · Science · doi:10.1126/science.abc8420 · Cited by 150 · see citing works
Matreyek, K. A., & Engelman, A. (2013) · Viruses · doi:10.3390/v5102483 · Cited by 142 · see citing works
Integrase, LEDGF/p75 and HIV replication
Poeschla, E. M. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-7540-5 · Cited by 127 · see citing works
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
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
Structure and architecture of immature and mature murine leukemia virus capsids
Qu, K., Glass, B., Doležal, M., Schur, F. K. M., Murciano, B., Rein, A. R., Rumlová, M., Ruml, T., Kräusslich, H., & Briggs, J. A. G. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1811580115 · Cited by 104 · see citing works
Harel, J., Rassart, E., & Jolicoeur, P. (1981) · Virology · doi:10.1016/0042-6822(81)90022-2 · Cited by 99 · 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
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
Self-citationLow, A., Okeoma, C. M., Lovšin, N., Heras, M. D. L., Taylor, T. H., Peterlin, B. M., Ross, S. R., & Fan, H. (2009) · Virology · doi:10.1016/j.virol.2008.11.051 · Cited by 83 · see citing works
Self-citationDisrupting HIV‐1 capsid formation causes cGAS sensing of viral DNA
Sumner, R. P., Harrison, L., Touizer, E., Peacock, T. P., Spencer, M. K., Zuliani‐Alvarez, L., & Towers, G. J. (2020) · The EMBO Journal · doi:10.15252/embj.2019103958 · Cited by 79 · see citing works
Viral Subversion of the Nuclear Pore Complex
Sage, V. L., & Mouland, A. J. (2013) · Viruses · doi:10.3390/v5082019 · Cited by 78 · see citing works
p12 Tethers the Murine Leukemia Virus Pre-integration Complex to Mitotic Chromosomes
Elis, E., Ehrlich, M., Prizan-Ravid, A., Laham-Karam, N., & Bacharach, E. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1003103 · Cited by 76 · see citing works
Aiyer, S., Swapna, G. V. T., Malani, N., Aramini, J. M., Schneider, W. M., Plumb, M. R., Ghanem, M., Larue, R. C., Sharma, A., Studamire, B., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku175 · Cited by 72 · see citing works
Structure of murine leukemia virus capsid C-terminal domain
Qu, K., Doležal, M., Schur, F. K. M., Murciano, B., Rumlová, M., Ruml, T., & Briggs, J. A. G. (2018) · Worldwide Protein Data Bank · doi:10.2210/pdb6gza/pdb · Cited by 72 · see citing works
Nucleic Acid Recognition Orchestrates the Anti-Viral Response to Retroviruses
Stavrou, S., Blouch, K., Kotla, S., Bass, A. R., & Ross, S. R. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.02.021 · Cited by 70 · see citing works
Self-citationStavrou, S., Aguilera, A. N., Blouch, K., & Ross, S. R. (2018) · mBio · doi:10.1128/mbio.00923-18 · Cited by 66 · see citing works
Self-citationHIV capsid and integration targeting
Engelman, A. N. (2021) · Viruses · doi:10.3390/v13010125 · Cited by 57 · see citing works
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
Kumar, S., Morrison, J. H., Dingli, D., & Poeschla, E. M. (2018) · Journal of Virology · doi:10.1128/jvi.00001-18 · Cited by 37 · see citing works
Critical Role of Dendritic Cells in Mouse Mammary Tumor Virus In Vivo Infection
Courreges, M. C., Burzyn, D., Nepomnaschy, I., Piazzón, I., & Ross, S. R. (2007) · Journal of Virology · doi:10.1128/jvi.02728-06 · Cited by 37 · see citing works
Self-citationLet me in: Control of HIV nuclear entry at the nuclear envelope
Bhargava, A., Lahaye, X., & Manel, N. (2018) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2018.02.006 · Cited by 32 · see citing works
Wanaguru, M., Barry, D. J., Benton, D. J., O’Reilly, N. J., & Bishop, K. N. (2018) · PLOS Pathogens · doi:10.1371/journal.ppat.1007117 · Cited by 27 · see citing works
Deaminase-Dead Mouse APOBEC3 Is an In Vivo Retroviral Restriction Factor
Stavrou, S., Zhao, W., Blouch, K., & Ross, S. R. (2018) · Journal of Virology · doi:10.1128/jvi.00168-18 · Cited by 25 · see citing works
Self-citationTzavaras, T., Eftaxia, S., Tavoulari, S., Hatzi, P., & Angelidis, C. (2003) · International Journal of Oncology · doi:10.3892/ijo.23.4.1237 · Cited by 22 · see citing works
Mendoza, R., Vaughan, A. E., & Miller, A. D. (2011) · Journal of Virology · doi:10.1128/jvi.05137-11 · Cited by 20 · see citing works
Martinelli, S. C., & Goff, S. P. (1990) · Virology · doi:10.1016/0042-6822(90)90062-v · Cited by 19 · see citing works
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 18 · see citing works
Murine Leukemia Virus P50 Protein Counteracts APOBEC3 by Blocking Its Packaging
Zhao, W., Akkawi, C., Mougel, M., & Ross, S. R. (2020) · Journal of Virology · doi:10.1128/jvi.00032-20 · Cited by 18 · see citing works
Self-citationHaugh, K. A., Ladinsky, M. S., Ullah, I., Stone, H. M., Pi, R., Gilardet, A., Grunst, M. W., Kumar, P., Björkman, P. J., Mothes, W., et al. (2021) · eLife · doi:10.7554/elife.64179 · Cited by 15 · see citing works
Repression of the Chromatin-Tethering Domain of Murine Leukemia Virus p12
Brzezinski, J. D., Modi, A., Liu, M., & Roth, M. J. (2016) · Journal of Virology · doi:10.1128/jvi.01084-16 · Cited by 8 · see citing works
The Host Range of Gammaretroviruses and Gammaretroviral Vectors Includes Post-Mitotic Neural Cells
Liu, X.-H., Xu, W., Russ, J. L., Eiden, L. E., & Eiden, M. V. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018072 · Cited by 8 · see citing works
Salas-Briceno, K., & Ross, S. R. (2021) · Journal of Virology · doi:10.1128/jvi.01244-21 · Cited by 7 · see citing works
Self-citation
Flagged first, then by citations
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Fu, L., Cheng, S., Riedel, D., Kopecny, L., Schuh, M., & Görlich, D. (2025) · Nature Structural & Molecular Biology · doi:10.1038/s41594-025-01684-5 · Cited by 6 · see citing works
Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication
Jehad, M. A., Ali, L. M., Pillai, V. N., Prabhu, S. G., Mustafa, F., & Rizvi, T. A. (2026) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuaf066 · Cited by 5 · see citing works
“Consistent with these findings, even in the case of a simple retrovirus such as MLV, it has recently been shown that the viral CA can gain access to the nucleus (Salas-Briceno et al. 2024 ), prompting further scrutiny of CA uncoating.”
Epigenetic mechanisms of retroviral regulation: a comparative review
Shin, S. Y., Tahmida, M., Beliakova‐Bethell, N., & LaMere, S. A. (2026) · Epigenetics & Chromatin · doi:10.1186/s13072-025-00659-6 · Cited by 3 · see citing works
van der Kuyl, A. C. (2026) · Pathogens · doi:10.3390/pathogens15010104 · Cited by 1 · see citing works
Zhou, J., Sekiguchi, Y., Sano, M., Nishimura, K., Hisatake, K., & Fukuda, A. (2024) · Scientific Reports · doi:10.1038/s41598-024-77508-1 · Cited by 1 · see citing works
The intersection of viral mimicry and nuclear entry
Dickson, C. F., Phalora, P. K., & Jacques, D. A. (2025) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2025.07.002
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Zhang, R. Z., Robben, L., Willey, A., Mele, V., Crow, E., Umana, S., Callahan, B., Arroyo, L., Graudin, G. W., Simmons, H. C., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.07.30.741819
- Authors
- Salas-Briceno, K., Zhao, W., & Ross, S. R.
- Affiliations
- University of Illinois Chicago (US)
- Corresponding author
- Ross, Susan R.
- Venue
- PLOS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2024-01-12
- Volume
- 20
- Issue
- 1
- Pages
- e1011640
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC10810426
- OpenAlex
- W4390831017
- Cited by
- 8
- References
- 48
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 1
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Update notices
- new_version (2024-01-25)
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIH/NIAID R01 AI174538, NIH/NIAID R01AI085015)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- murine leukemia virus, dendritic cells, nucleoporins, nuclear pore complex, reverse transcription, viral uncoating, preintegration complex, nuclear entry, cell division, Nup358, Nup62, retroviral integration
- MeSH terms
- Animals, Dendritic Cells, DNA, Leukemia Virus, Murine, Retroviridae, Viral Proteins, HIV Infections, Nuclear Pore Complex Proteins, Capsid Proteins, NIH 3T3 Cells, Mice
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