Nucleic Acids Research Advance Access published online on February 22, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn069
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Molecular Biology |
Nucleocapsid mutations turn HIV-1 into a DNA-containing virus
1Université Montpellier 1, Centre d’études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS), 2CNRS, UMR 5236, CPBS, 4 Bd Henri IV, CS69033, 34965 Montpellier, 3Université Montpellier 2, CPBS, 34095 Montpellier and 4LaboRetro, Unité de virologie humaine INSERM U758, IFR128, ENS, 46 allée d’Italie, Lyon, France
*To whom correspondence should be addressed. Tel: +33 4 67 60 0232; Fax: +33 4 67 60 4420; Email: mmougel{at}univ-montp1.fr
Received January 14, 2008. Revised February 4, 2008. Accepted February 5, 2008.
Retroviruses replicate by converting their positive sense genomic RNA into double-stranded DNA that is subsequently integrated into the host genome. This conversion is catalyzed by reverse transcriptase (RT) early after virus entry into the target cell and is chaperoned by the nucleocapsid protein (NC). In HIV-1, NC is composed of small basic domains flanking two highly conserved CCHC zinc fingers that specifically interact with the genomic RNA and RT. Through specific interactions with the genomic RNA and RT, and possibly with cellular factors, the NC zinc fingers were found to play critical roles in HIV-1 assembly and budding, and later in proviral DNA synthesis and integration. Therefore, intact NC zinc fingers are needed throughout the virus replication cycle. Here, we report for the first time that deleting either one or the two NC zinc fingers leads to an unexpected premature viral DNA synthesis in virus producer cells and the production of noninfectious particles with a high level of viral DNA. In addition to providing the first example of reverse transcription during the late steps of HIV-1 replication, these findings emphasize the fact that the NC zinc fingers are a major target for new drugs against HIV-1.
The authors wish it to be known that, in their opinion, the second and the third authors be regarded as joint Second Authors.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Lazarczyk and M. Favre Role of Zn2+ Ions in Host-Virus Interactions J. Virol., December 1, 2008; 82(23): 11486 - 11494. [Full Text] [PDF]
|
|
|
|
|
|
J. A. Thomas, W. J. Bosche, T. L. Shatzer, D. G. Johnson, and R. J. Gorelick Mutations in Human Immunodeficiency Virus Type 1 Nucleocapsid Protein Zinc Fingers Cause Premature Reverse Transcription J. Virol., October 1, 2008; 82(19): 9318 - 9328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Didierlaurent, L. Houzet, Z. Morichaud, J.-L. Darlix, and M. Mougel The conserved N-terminal basic residues and zinc-finger motifs of HIV-1 nucleocapsid restrict the viral cDNA synthesis during virus formation and maturation Nucleic Acids Res., August 1, 2008; 36(14): 4745 - 4753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kuciak, C. Gabus, R. Ivanyi-Nagy, K. Semrad, R. Storchak, O. Chaloin, S. Muller, Y. Mely, and J.-L. Darlix The HIV-1 transcriptional activator Tat has potent nucleic acid chaperoning activities in vitro Nucleic Acids Res., June 1, 2008; 36(10): 3389 - 3400. [Abstract] [Full Text] [PDF]
|
|