Document Detail


Cell cycle arrest in G2/M promotes early steps of infection by human immunodeficiency virus.
MedLine Citation:
PMID:  15827184     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have identified four small molecules that boost transduction of cells by human immunodeficiency virus (HIV) and investigated their mechanism of action. These molecules include etoposide and camptothecin, which induce DNA damage by inhibiting religation of cleaved topoisomerase-DNA complexes, taxol, which interferes with the function of microtubules, and aphidicolin, which inhibits DNA polymerases. All four compounds arrest the cell cycle at G2/M, though in addition high concentrations of aphidicolin arrest in G1. We find that early events of HIV replication, including synthesis of late reverse transcription products, two-long terminal repeat circles, and integrated proviruses, were increased after treatment of cells with concentrations of each compound that arrested in G2/M. Stimulation was seen for both transformed cell lines (293T and HeLa cells) and primary cells (IMR90 lung fibroblasts). Arrest in G1 with high concentrations of aphidicolin boosted transduction, though not much as with lower concentrations that arrested in G2/M. Arrest of IMR90 cells in G1 by serum starvation and contact inhibition reduced transduction. Previously, the proteasome inhibitor MG132 was reported to increase HIV infection-here we investigated the effects of combinations of the cell cycle inhibitors with MG132 and obtained data suggesting that MG132 may also boost transduction by causing G2/M cell cycle arrest. These data document that cell cycle arrest in G2/M boosts the early steps of HIV infection and suggests methods for increasing transduction with HIV-based vectors.
Authors:
Bettina Groschel; Frederic Bushman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of virology     Volume:  79     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-04-13     Completed Date:  2005-06-03     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5695-704     Citation Subset:  IM    
Affiliation:
University of Pennsylvania School of Medicine, Department of Microbiology, 3610 Hamilton Walk, Philadelphia, PA 19104-6076, USA.
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MeSH Terms
Descriptor/Qualifier:
Aphidicolin / pharmacology
Camptothecin / pharmacology
Cell Cycle / drug effects*
Cell Division / drug effects
Cell Line
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology
Etoposide / pharmacology
G2 Phase / drug effects
HIV / genetics,  physiology*
HIV Infections / virology*
Humans
Nucleic Acid Synthesis Inhibitors / pharmacology
Paclitaxel / pharmacology
Time Factors
Transduction, Genetic
Virus Replication
Grant Support
ID/Acronym/Agency:
AI34786/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Nucleic Acid Synthesis Inhibitors; 33069-62-4/Paclitaxel; 33419-42-0/Etoposide; 38966-21-1/Aphidicolin; 7689-03-4/Camptothecin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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