Role of HIV-1 Nucleocapsid Protein in HIV-1 Reverse Transcription

Overview

Journal RNA Biol

Specialty Molecular Biology

Date 2010 Dec 17

PMID 21160280

Citations 105

Authors

Judith G Levin

Mithun Mitra

Anjali Mascarenhas

Karin Musier-Forsyth

Affiliations

Soon will be listed here.

Abstract

The HIV-1 nucleocapsid protein (NC) is a nucleic acid chaperone, which remodels nucleic acid structures so that the most thermodynamically stable conformations are formed. This activity is essential for virus replication and has a critical role in mediating highly specific and efficient reverse transcription. NC's function in this process depends upon three properties: (1) ability to aggregate nucleic acids; (2) moderate duplex destabilization activity; and (3) rapid on-off binding kinetics. Here, we present a detailed molecular analysis of the individual events that occur during viral DNA synthesis and show how NC's properties are important for almost every step in the pathway. Finally, we also review biological aspects of reverse transcription during infection and the interplay between NC, reverse transcriptase, and human APOBEC3G, an HIV-1 restriction factor that inhibits reverse transcription and virus replication in the absence of the HIV-1 Vif protein.

Citing Articles

Exploring HIV-1 Maturation: A New Frontier in Antiviral Development.

McGraw A, Hillmer G, Medehincu S, Hikichi Y, Gagliardi S, Narayan K Viruses. 2024; 16(9).

PMID: 39339899 PMC: 11437483. DOI: 10.3390/v16091423.

Cationic Residues of the HIV-1 Nucleocapsid Protein Enable DNA Condensation to Maintain Viral Core Particle Stability during Reverse Transcription.

Gien H, Morse M, McCauley M, Rouzina I, Gorelick R, Williams M Viruses. 2024; 16(6).

PMID: 38932164 PMC: 11209390. DOI: 10.3390/v16060872.

Tribute to Dr. Judith G. Levin (1934-2023).

Musier-Forsyth K, Rein A, Freed E Viruses. 2024; 16(2).

PMID: 38399955 PMC: 10893463. DOI: 10.3390/v16020178.

Structural and Synthetic Aspects of Small Ring Oxa- and Aza-Heterocyclic Ring Systems as Antiviral Activities.

Manna S, Das K, Santra S, Nosova E, Zyryanov G, Halder S Viruses. 2023; 15(9).

PMID: 37766233 PMC: 10536032. DOI: 10.3390/v15091826.

Multifaceted Aspects of HIV-1 Nucleocapsid Inhibition by TAR-Targeting Peptidyl-Anthraquinones Bearing Terminal Aromatic Moieties.

Sosic A, Frecentese F, Olivato G, Rollo D, Carraro C, Gamba E Viruses. 2022; 14(10).

PMID: 36298688 PMC: 9607300. DOI: 10.3390/v14102133.

References

Liu H, Zeng Y, Landes C, Kim Y, Zhu Y, Ma X . Insights on the role of nucleic acid/protein interactions in chaperoned nucleic acid rearrangements of HIV-1 reverse transcription. Proc Natl Acad Sci U S A. 2007; 104(13):5261-7. PMC: 1828707. DOI: 10.1073/pnas.0700166104. View

Rodriguez-Rodriguez L, Tsuchihashi Z, Fuentes G, Bambara R, Fay P . Influence of human immunodeficiency virus nucleocapsid protein on synthesis and strand transfer by the reverse transcriptase in vitro. J Biol Chem. 1995; 270(25):15005-11. DOI: 10.1074/jbc.270.25.15005. View

Bolinger C, Boris-Lawrie K . Mechanisms employed by retroviruses to exploit host factors for translational control of a complicated proteome. Retrovirology. 2009; 6:8. PMC: 2657110. DOI: 10.1186/1742-4690-6-8. View

Zaitseva L, Myers R, Fassati A . tRNAs promote nuclear import of HIV-1 intracellular reverse transcription complexes. PLoS Biol. 2006; 4(10):e332. PMC: 1584419. DOI: 10.1371/journal.pbio.0040332. View

Zennou V, Petit C, Guetard D, Nerhbass U, Montagnier L, Charneau P . HIV-1 genome nuclear import is mediated by a central DNA flap. Cell. 2000; 101(2):173-85. DOI: 10.1016/S0092-8674(00)80828-4. View

Rulli Jr S, Hibbert C, Mirro J, Pederson T, Biswal S, Rein A . Selective and nonselective packaging of cellular RNAs in retrovirus particles. J Virol. 2007; 81(12):6623-31. PMC: 1900105. DOI: 10.1128/JVI.02833-06. View

Azoulay J, Clamme J, Darlix J, Roques B, Mely Y . Destabilization of the HIV-1 complementary sequence of TAR by the nucleocapsid protein through activation of conformational fluctuations. J Mol Biol. 2003; 326(3):691-700. DOI: 10.1016/s0022-2836(02)01430-4. View

Rothenberg E, Smotkin D, Baltimore D, Weinberg R . In vitro synthesis of infectious DNA of murine leukaemia virus. Nature. 1977; 269(5624):122-6. DOI: 10.1038/269122a0. View

LEVIN J, Grimley P, Ramseur J, Berezesky I . Deficiency of 60 to 70S RNA in murine leukemia virus particles assembled in cells treated with actinomycin D. J Virol. 1974; 14(1):152-61. PMC: 355489. DOI: 10.1128/JVI.14.1.152-161.1974. View

10.

Li X, Guo F, Zhang L, Kleiman L, Cen S . APOBEC3G inhibits DNA strand transfer during HIV-1 reverse transcription. J Biol Chem. 2007; 282(44):32065-74. DOI: 10.1074/jbc.M703423200. View

11.

Wu T, Heilman-Miller S, Levin J . Effects of nucleic acid local structure and magnesium ions on minus-strand transfer mediated by the nucleic acid chaperone activity of HIV-1 nucleocapsid protein. Nucleic Acids Res. 2007; 35(12):3974-87. PMC: 1919501. DOI: 10.1093/nar/gkm375. View

12.

Wurtzer S, Goubard A, Mammano F, Saragosti S, Lecossier D, Hance A . Functional central polypurine tract provides downstream protection of the human immunodeficiency virus type 1 genome from editing by APOBEC3G and APOBEC3B. J Virol. 2006; 80(7):3679-83. PMC: 1440420. DOI: 10.1128/JVI.80.7.3679-3683.2006. View

13.

Hu W, Temin H . Genetic consequences of packaging two RNA genomes in one retroviral particle: pseudodiploidy and high rate of genetic recombination. Proc Natl Acad Sci U S A. 1990; 87(4):1556-60. PMC: 53514. DOI: 10.1073/pnas.87.4.1556. View

14.

Gorelick R, Gagliardi T, Bosche W, Wiltrout T, Coren L, Chabot D . Strict conservation of the retroviral nucleocapsid protein zinc finger is strongly influenced by its role in viral infection processes: characterization of HIV-1 particles containing mutant nucleocapsid zinc-coordinating sequences. Virology. 1999; 256(1):92-104. DOI: 10.1006/viro.1999.9629. View

15.

Henriet S, Mercenne G, Bernacchi S, Paillart J, Marquet R . Tumultuous relationship between the human immunodeficiency virus type 1 viral infectivity factor (Vif) and the human APOBEC-3G and APOBEC-3F restriction factors. Microbiol Mol Biol Rev. 2009; 73(2):211-32. PMC: 2698415. DOI: 10.1128/MMBR.00040-08. View

16.

Dussupt V, Javid M, Abou-Jaoude G, Jadwin J, de la Cruz J, Nagashima K . The nucleocapsid region of HIV-1 Gag cooperates with the PTAP and LYPXnL late domains to recruit the cellular machinery necessary for viral budding. PLoS Pathog. 2009; 5(3):e1000339. PMC: 2651531. DOI: 10.1371/journal.ppat.1000339. View

17.

Sheehy A, Gaddis N, Choi J, Malim M . Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature. 2002; 418(6898):646-50. DOI: 10.1038/nature00939. View

18.

Cruceanu M, Gorelick R, Musier-Forsyth K, Rouzina I, Williams M . Rapid kinetics of protein-nucleic acid interaction is a major component of HIV-1 nucleocapsid protein's nucleic acid chaperone function. J Mol Biol. 2006; 363(5):867-77. DOI: 10.1016/j.jmb.2006.08.070. View

19.

Grohmann D, Godet J, Mely Y, Darlix J, Restle T . HIV-1 nucleocapsid traps reverse transcriptase on nucleic acid substrates. Biochemistry. 2008; 47(46):12230-40. DOI: 10.1021/bi801386r. View

20.

Song M, Balakrishnan M, Gorelick R, Bambara R . A succession of mechanisms stimulate efficient reconstituted HIV-1 minus strand strong stop DNA transfer. Biochemistry. 2009; 48(8):1810-9. PMC: 2881584. DOI: 10.1021/bi802149j. View