Cell cycle regulation of human immunodeficiency virus type 1 integration in T cells: antagonistic effects of nuclear envelope breakdown and chromatin condensation.
We examined the influence of mitosis on the kinetics of human immunodeficiency virus type 1 integration in T cells. Single-round infection of cells arrested in G1b or allowed to synchronously proceed through division showed that mitosis delays virus integration until 18-24 h postinfection, whereas integration reaches maximum levels by 15 h in G1b-arrested cells. Subcellular fractionation of metaphase-arrested cells indicated that, while nuclear envelope disassembly facilitates docking of viral DNA to chromatin, chromosome condensation directly antagonizes and therefore delays integration. As a result of the balance between the two effects, virus integration efficiency is eventually up to threefold greater in dividing cells. At the single-cell level, using a green fluorescent protein-expressing reporter virus, we found that passage through mitosis leads to prominent asymmetric segregation of the viral genome in daughter cells without interfering with provirus expression.
EMI-0013 Institut National de la Santé et de la Recherche Médicale-Université Paris 7, 75010 Paris, France. karim.mannioui@chu-stlouis.fr
Abdelkrim
A
Mannioui
Cecile
C
Schiffer
Nathalie
N
Felix
Elisabeth
E
Nelson
Audrey
A
Brussel
Pierre
P
Sonigo
Jean Claude
JC
Gluckman
Bruno
B
Canque
D000818:Animals; D002453:Cell Cycle; D002843:Chromatin / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D008938:Mitosis; D009685:Nuclear Envelope / Q000378:metabolism; D013601:T-Lymphocytes / Q000821:virology*; D016662:Virus Integration
D002843:Chromatin; D004279:DNA, Viral