Research article summary (published 30 Oct 2009):

Regulation of HIV-1 transcription at 3% versus 21% oxygen concentration.

Full Abstract

HIV transcription is induced by the HIV-1 Tat protein, in concert with cellular co-factors including CDK9, CDK2, NF-kappaB, and others. The cells of most of the body's organs are exposed to approximately 3-6% oxygen, but most in vitro studies of HIV replication are conducted at 21% oxygen. We hypothesized that activities of host cell factors involved in HIV-1 replication may differ at 3% versus 21% O(2), and that such differences may affect HIV-1 replication. Here we show that Tat-induced HIV-1 transcription was reduced at 3% O(2) compared to 21% O(2). HIV-1 replication was also reduced in acutely or chronically infected cells cultured at 3% O(2) compared to 21% O(2). This reduction was not due the decreased cell growth or increased cellular toxicity and also not due to the induction of hypoxic response. At 3% O(2), the activity of CDK9/cyclin T1 was inhibited and Sp1 activity was reduced, whereas the activity of other host cell factors such as CDK2 or NF-kappaB was not affected. CDK9-specific inhibitor ARC was much less efficient at 3% compared to 21% O(2) and also expression of CDK9/cyclin T1-dependent IkappaB inhibitor alpha was repressed. Our results suggest that lower HIV-1 transcription at 3% O(2) compared to 21% O(2) may be mediated by lower activity of CDK9/cyclin T1 and Sp1 at 3% O(2) and that additional host cell factors such as CDK2 and NF-kappaB might be major regulators of HIV-1 transcription at low O(2) concentrations.

Author information

Author/s: Charles, Sharroya (S); Ammosova, Tatyana (T); Cardenas, Jessica (J); Foster, Altreisha (A); Rotimi, Jamie (J); Jerebtsova, Marina (M); Ayodeji, Abisola A (AA); Niu, Xiaomei (X); Ray, Patricio E (PE); Gordeuk, Victor R (VR); Kashanchi, Fatah (F); Nekhai, Sergei (S);

Affiliation: Center for Sickle Cell Disease, Howard University, Washington, DC 20001, USA.

Grants: 2 M01 RR10284 (Agency:NCRR NIH HHS) ; 2 R25 HL003679-08 (Agency:NHLBI NIH HHS) ; GM 082325-01 (Agency:NIGMS NIH HHS) ; R01 DK49419 (Agency:NIDDK NIH HHS) ; R01 HL55605 (Agency:NHLBI NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.

Journal: Journal of cellular physiology (J Cell Physiol), published in United States. (Language: eng)

Reference: 2009-Nov; vol 221 (issue 2) : pp 469-79

Dates: Created 2009/08/27; Completed 2009/09/09;

PMID: 19626680, status: MEDLINE (last retrieval date: 9/9/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Cell Line Cell Proliferation - drug effects Cell Survival - drug effects Cyclin-Dependent Kinase 2 - metabolism Cyclin-Dependent Kinase 9 - metabolism Cyclins - metabolism Gene Expression Regulation, Viral - drug effects HIV-1 - drug effects; genetics; physiology Humans

Hypoxia-Inducible Factor 1, alpha Subunit - metabolism Monocytes - cytology; drug effects NF-kappa B - metabolism Oxygen - pharmacology Sp1 Transcription Factor - metabolism T-Lymphocytes - cytology; drug effects Transcription, Genetic - drug effects Virus Replication - drug effects tat Gene Products, Human Immunodeficiency Virus - metabolism

Associated Chemicals: CCNT1 protein, human (0) ; Cyclins (0) ; HIF1A protein, human (0) ; Hypoxia-Inducible Factor 1, alpha Subunit (0) ; NF-kappa B (0) ; Sp1 Transcription Factor (0) ; tat Gene Products, Human Immunodeficiency Virus (0) ; Oxygen (7782-44-7) ; CDK2 protein, human (EC 2.7.1.37) ; Cyclin-Dependent Kinase 2 (EC 2.7.1.37) ; Cyclin-Dependent Kinase 9 (EC 2.7.1.37)

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