The Vpr protein of human immunodeficiency virus type 1 influences nuclear localization of viral nucleic acids in nondividing host cells.
Open accessAbstract
The replication of human immunodeficiency virus type 1 (HIV-1) in nondividing host cells such as those of macrophage lineage is an important feature of AIDS pathogenesis. The pattern of HIV-1 replication is dictated, in part, by the nucleophilic property of the viral gag matrix (MA) protein, a component of the viral preintegration complex that facilitates nuclear localization of viral nucleic acids in the absence of mitosis. We now identify the accessory viral protein Vpr, as a second nucleophilic component that influences nuclear localization of viral nucleic acids in nondividing cells. Reverse transcription and nuclear localization of viral nucleic acids following infection of cells by viruses lacking Vpr or viruses containing mutations in a gag MA nuclear localization sequence were indistinguishable from the pattern observed in cells infected by wild-type HIV-1. These viruses retained the ability to replicate in both dividing and nondividing host cells including monocyte-derived macrophages. In contrast, introduction of both gag MA and Vpr mutations in HIV-1 attenuated nuclear localization of viral nucleic acids in nondividing cells and virus replication in monocyte-derived macrophages. These studies demonstrate redundant nucleophilic determinants of HIV-1 that independently permit nuclear localization of viral nucleic acids and virus replication in nondividing cells such as monocyte-derived macrophages. In addition, these studies provide a defined function for an accessory gene product of HIV-1.
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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 [8]
Cites
Active nuclear import of human immunodeficiency virus type 1 preintegration complexes.
Bukrinsky, M. I., Sharova, N., Dempsey, M. P., Stanwick, T. L., Bukrinskaya, A. G., Haggerty, S., & Stevenson, M. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.14.6580 · Cited by 607 · see citing works
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In Vivo Gene Delivery and Stable Transduction of Nondividing Cells by a Lentiviral Vector
Naldini, L., Blömer, U., Gallay, P., Ory, D., Mulligan, R., Gage, F. H., Verma, I. M., & Trono, D. (1996) · Science · doi:10.1126/science.272.5259.263 · Cited by 4,903 · see citing works
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 Gag proteins: diverse functions in the virus life cycle
Freed, E. O. (1998) · Virology · doi:10.1006/viro.1998.9398 · Cited by 717 · see citing works
Cytokine Signals Are Sufficient for HIV-1 Infection of Resting Human T Lymphocytes
Unutmaz, D., KewalRamani, V. N., Marmon, S., & Littman, D. R. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.11.1735 · Cited by 427 · see citing works
Self-citationLentiviral Vectors in Gene Therapy: Their Current Status and Future Potential
Escors, D., & Breckpot, K. (2010) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-010-0063-4 · Cited by 344 · see citing works
Llano, M., Vanegas, M., Fregoso, O., Saenz, D., Chung, S., Peretz, M., & Poeschla, E. M. (2004) · Journal of Virology · doi:10.1128/jvi.78.17.9524-9537.2004 · Cited by 305 · see citing works
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
Differential membrane binding of the human immunodeficiency virus type 1 matrix protein
Zhou, W., & Resh, M. D. (1996) · Journal of Virology · doi:10.1128/jvi.70.12.8540-8548.1996 · Cited by 226 · see citing works
HIV Integration Targeting: A Pathway Involving Transportin-3 and the Nuclear Pore Protein RanBP2
Ocwieja, K. E., Brady, T. L., Ronen, K., Huegel, A., Roth, S. L., Schaller, T., James, L. C., Towers, G. J., Young, J. A. T., Chanda, S. K., et al. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1001313 · Cited by 212 · see citing works
HIV-1 Vpr function is mediated by interaction with the damage-specific DNA-binding protein DDB1
Schröfelbauer, B., Hakata, Y., & Landau, N. R. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610167104 · Cited by 187 · see citing works
Eckstein, D. A., Sherman, M. P., Penn, M. L., Chin, P. S., De Noronha, C. M. C., Greene, W. C., & Goldsmith, M. A. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.10.1407 · Cited by 124 · see citing works
Bergamaschi, A., Ayinde, D., David, A., Le Rouzic, E., Morel, M., Collin, G., Descamps, D., Damond, F., Brun-Vezinet, F., Nisole, S., et al. (2009) · Journal of Virology · doi:10.1128/jvi.00187-09 · Cited by 121 · see citing works
Zhang, S., Feng, Y., Narayan, O., & Zhao, L.-J. (2001) · Gene · doi:10.1016/s0378-1119(00)00583-7 · Cited by 106 · see citing works
Cell cycle dependence of foamy retrovirus infection
Bieniasz, P. D., Weiss, R. A., & McClure, M. O. (1995) · Journal of Virology · doi:10.1128/jvi.69.11.7295-7299.1995 · Cited by 94 · see citing works
Retrovirus and lentivirus vector design and methods of cell conditioning
Cooray, S., Howe, S. J., & Thrasher, A. J. (2012) · Methods in Enzymology · doi:10.1016/b978-0-12-386509-0.00003-x · Cited by 65 · see citing works
Efficient gene expression from integration-deficient lentiviral vectors in the spinal cord
Peluffo, H., Foster, E., Ahmed, S. G., Lago, N., Hutson, T. H., Moon, L., Yip, P., Wanisch, K., Caraballo-Miralles, V, Olmos, G., et al. (2013) · Gene Therapy · doi:10.1038/gt.2012.78 · Cited by 40 · see citing works
Wang, Q., & Su, L. (2019) · mBio · doi:10.1128/mbio.01344-19 · Cited by 34 · see citing works
Hakata, Y., Miyazawa, M., & Landau, N. R. (2014) · Virology Journal · doi:10.1186/1743-422x-11-108 · Cited by 13 · see citing works
- Authors
- Heinzinger, N. K., Bukinsky, M. I., Haggerty, S. A., Ragland, A. M., Kewalramani, V, Lee, M. A., Gendelman, H. E., Ratner, L., Stevenson, M., & Emerman, M.
- Affiliations
- University of Nebraska Medical Center (US)
- École Polytechnique Fédérale de Lausanne (CH)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1994-07-19
- Volume
- 91
- Issue
- 15
- Pages
- 7311-7315
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC44389
- OpenAlex
- W2001243226
- Cited by
- 854
- References
- 1
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 7 · 2022: 3 · 2021: 6 · 2020: 6 · 2019: 13 · 2018: 6 · 2017: 8 · 2016: 9 · 2015: 20 · 2014: 21 · 2013: 20 · 2012: 25
- FWCI
- 17.12
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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
- HIV-1 Vpr protein, monocyte-derived macrophages, preintegration complex, HIV-1 replication, reverse transcription
- MeSH terms
- Base Sequence, Cell Division, Cell Line, Cell Nucleus, Cloning, Molecular, DNA, Viral, Humans, Molecular Sequence Data, Mutation, HIV-1, Polymerase Chain Reaction, Gene Products, vpr, vpr Gene Products, Human Immunodeficiency Virus
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