Nucleocapsid mutations turn HIV-1 into a DNA-containing virus.
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.
Houzet
Laurent
L
Université Montpellier 1, Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS), Lyon, France.
Morichaud
Zakia
Z
Didierlaurent
Ludovic
L
Muriaux
Delphine
D
Darlix
Jean-Luc
JL
Mougel
Marylène
M
D002460:Cell Line; D004267:DNA Viruses / Q000235:genetics; D004279:DNA, Viral / Q000096:biosynthesis* / Q000378:metabolism; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D009154:Mutation; D012367:RNA, Viral / Q000378:metabolism; D017384:Sequence Deletion; D014771:Virion / Q000235:genetics; D019065:Virus Assembly; D014779:Virus Replication; D016335:Zinc Fingers; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
D004279:DNA, Viral; C071884:NCP7 protein, Human immunodeficiency virus 1; D012367:RNA, Viral; D054301:gag Gene Products, Human Immunodeficiency Virus; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase