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Oxygen Levels and HIV‐1 Transcription
Author(s) -
Charles Sharroya M,
Ammosova Tatyana,
Cardenas Jessica,
Jerebtsova Marina,
Niu Xiaomei,
Ray Patricio,
Kashanchi Fatah,
Gordeuk Victor
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.899.3
Subject(s) - transcription (linguistics) , rna polymerase ii , biology , microbiology and biotechnology , chemistry , gene expression , gene , promoter , biochemistry , philosophy , linguistics
Cellular metabolism of macrophages and T cells cultured at atmospheric 21% O 2 is significantly different from cells cultured at 3–6% O 2 . HIV‐1 Tat induces transcription of HIV‐1 genes by recruiting host cell CDK9/cyclin T1 to TAR RNA. Our recent studies indicate that HIV‐1 transcription is also regulated by protein phosphatase‐1 (PP1). PP1 interacts with the Tat protein and disruption of this association prevents induction of HIV‐1 transcription. Here we analyzed the effect of 3% versus 21% O 2 concentration on HIV‐1 transcription and replication and cellular activities of CDK9 and PP1. Using reporter assays, we found that 3% O 2 inhibited HIV‐1 Tat‐induced transcription and viral replication. CDK9 activity but not CDK2 activity was inhibited in the cells cultured under 3% O 2 . Although PP1 expression level was not decreased, its activity was greatly reduced under 3% O 2 which was due to the changes in its conformation and sensitivity to trypsin treatment. We previously showed that PP1 dephosphorylates CDK9, and decreased PP1 activity during hypoxia adversely affected CDK9 activity resulting in inhibition of HIV‐1 transcription. Our results indicate that HIV‐1 transcription is suppressed at physiological oxygen levels likely due to deregulation of host cell factors CDK9 and PP1 thus providing a new insight into the HIV‐1 latency.