Nucleic Acids Research Advance Access originally published online on February 22, 2008
Nucleic Acids Research 2008 36(7):2311-2319; doi:10.1093/nar/gkn069
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Nucleic Acids Research, 2008, Vol. 36, No. 7 2311-2319
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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
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