Entry and transcription as key determinants of differences in CD4 T-cell permissiveness to human immunodeficiency virus type 1 infection.

Details

Serval ID
serval:BIB_92680CCF2EA7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Entry and transcription as key determinants of differences in CD4 T-cell permissiveness to human immunodeficiency virus type 1 infection.
Journal
Journal of virology
Author(s)
Ciuffi A., Bleiber G., Muñoz M., Martinez R., Loeuillet C., Rehr M., Fischer M., Günthard H.F., Oxenius A., Meylan P., Bonhoeffer S., Trono D., Telenti A.
ISSN
0022-538X
Publication state
Published
Issued date
2004
Peer-reviewed
Oui
Volume
78
Number
19
Pages
10747-54
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Abstract
Isolated primary human cells from different donors vary in their permissiveness-the ability of cells to be infected and sustain the replication of human immunodeficiency virus type 1 (HIV-1). We used replicating HIV-1 and single-cycle lentivirus vectors in a population approach to identify polymorphic steps during viral replication. We found that phytohemagglutinin-stimulated CD4(+) CD45RO(+) CD57(-) T cells from healthy blood donors (n = 128) exhibited a 5.2-log-unit range in virus production. For 20 selected donors representing the spectrum of CD4 T-cell permissiveness, we could attribute up to 42% of the total variance in virus production to entry factors and 48% to postentry steps. Efficacy at key intracellular steps of the replicative cycle (reverse transcription, integration, transcription and splicing, translation, and budding and release) varied from 0.71 to 1.45 log units among donors. However, interindividual differences in transcription efficiency alone accounted for 64 to 83% of the total variance in virus production that was attributable to postentry factors. While vesicular stomatitis virus G protein-mediated fusion was more efficacious than CCR5/CD4 entry, the latter resulted in greater transcriptional activity per proviral copy. The phenotype of provirus transcription was stable over time, indicating that it represents a genetic trait.
Keywords
Antigens, CD4, Antigens, CD45, Antigens, CD57, Biological Transport, CD4-Positive T-Lymphocytes, Cells, Cultured, DNA, Viral, HIV Core Protein p24, HIV-1, Humans, Protein Biosynthesis, Protein Tyrosine Phosphatase, Non-Receptor Type 1, Proviruses, RNA Splicing, RNA, Viral, Receptors, CCR5, Time Factors, Transcription, Genetic, Vesicular stomatitis Indiana virus, Virus Integration, Virus Replication
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 15:46
Last modification date
20/08/2019 15:55
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