Cited by 854HIV Research and TreatmentHIV/AIDS drug development and treatmentT-cell and Retrovirus Studies

The Vpr protein of human immunodeficiency virus type 1 influences nuclear localization of viral nucleic acids in nondividing host cells.

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Heinzinger, N K, Bukinsky, M I, Haggerty, S A, Ragland, A M, Kewalramani, V, Lee, M A, Gendelman, H E, Ratner, L +2 more·1994·Proceedings of the National Academy of Sciences

Abstract

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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Crossref · 10.1073/pnas.91.15.7311

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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]

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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
Published
1994-07-19
Volume
91
Issue
15
Pages
7311-7315
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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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