Sterol regulatory element-binding protein 2 couples HIV-1 transcription to cholesterol homeostasis and T cell activation

Harry E. Taylor, Michael E. Linde, Atanu K. Khatua, Waldemar Popik, James E K Hildreth

    Research output: Contribution to journalArticle

    Abstract

    Cholesterol plays an essential role in the life cycle of several enveloped viruses. Many of these viruses manipulate host cholesterol metabolism to facilitate their replication. HIV-1 infection of CD4 + T cells activates the sterol regulatory element-binding protein 2 (SREBP2) transcriptional program, which includes genes involved in cholesterol homeostasis. However, the role of SREBP2-dependent transcription in HIV-1 biology has not been fully examined. Here, we identify TFII-I, a gene critical for HIV-1 transcription in activated T cells, as a novel SREBP2 target gene. We found TFII-I expression increased after HIV-1 infection or activation of human primary CD4 + T cells. We show that inhibition of SREBP2 activity reduced TFII-I induction in response to these stimuli. More importantly, small interfering RNA (siRNA)-mediated gene silencing of either SREBP2 or TFII-I significantly reduced HIV-1 production in CD4 + T cells. We also found that TFII-I potentiates Tat-dependent viral gene expression, consistent with a role at the level of HIV-1 transcription. Collectively, our results demonstrate for the first time that HIV-1 transcription in T cells is linked to cholesterol homeostasis through control of TFII-I expression by SREBP2.

    Original languageEnglish (US)
    Pages (from-to)7699-7709
    Number of pages11
    JournalJournal of Virology
    Volume85
    Issue number15
    DOIs
    StatePublished - Aug 2011

    Fingerprint

    Sterol Regulatory Element Binding Protein 2
    Human immunodeficiency virus 1
    sterols
    HIV-1
    binding proteins
    homeostasis
    Homeostasis
    transcription (genetics)
    T-lymphocytes
    Cholesterol
    cholesterol
    T-Lymphocytes
    HIV Infections
    Genes
    Viruses
    viruses
    cholesterol metabolism
    genes
    Viral Genes
    Gene Silencing

    ASJC Scopus subject areas

    • Immunology
    • Virology

    Cite this

    Sterol regulatory element-binding protein 2 couples HIV-1 transcription to cholesterol homeostasis and T cell activation. / Taylor, Harry E.; Linde, Michael E.; Khatua, Atanu K.; Popik, Waldemar; Hildreth, James E K.

    In: Journal of Virology, Vol. 85, No. 15, 08.2011, p. 7699-7709.

    Research output: Contribution to journalArticle

    Taylor, Harry E. ; Linde, Michael E. ; Khatua, Atanu K. ; Popik, Waldemar ; Hildreth, James E K. / Sterol regulatory element-binding protein 2 couples HIV-1 transcription to cholesterol homeostasis and T cell activation. In: Journal of Virology. 2011 ; Vol. 85, No. 15. pp. 7699-7709.
    @article{88659715f9ad44369d3c79645acee196,
    title = "Sterol regulatory element-binding protein 2 couples HIV-1 transcription to cholesterol homeostasis and T cell activation",
    abstract = "Cholesterol plays an essential role in the life cycle of several enveloped viruses. Many of these viruses manipulate host cholesterol metabolism to facilitate their replication. HIV-1 infection of CD4 + T cells activates the sterol regulatory element-binding protein 2 (SREBP2) transcriptional program, which includes genes involved in cholesterol homeostasis. However, the role of SREBP2-dependent transcription in HIV-1 biology has not been fully examined. Here, we identify TFII-I, a gene critical for HIV-1 transcription in activated T cells, as a novel SREBP2 target gene. We found TFII-I expression increased after HIV-1 infection or activation of human primary CD4 + T cells. We show that inhibition of SREBP2 activity reduced TFII-I induction in response to these stimuli. More importantly, small interfering RNA (siRNA)-mediated gene silencing of either SREBP2 or TFII-I significantly reduced HIV-1 production in CD4 + T cells. We also found that TFII-I potentiates Tat-dependent viral gene expression, consistent with a role at the level of HIV-1 transcription. Collectively, our results demonstrate for the first time that HIV-1 transcription in T cells is linked to cholesterol homeostasis through control of TFII-I expression by SREBP2.",
    author = "Taylor, {Harry E.} and Linde, {Michael E.} and Khatua, {Atanu K.} and Waldemar Popik and Hildreth, {James E K}",
    year = "2011",
    month = "8",
    doi = "10.1128/JVI.00337-11",
    language = "English (US)",
    volume = "85",
    pages = "7699--7709",
    journal = "Journal of Virology",
    issn = "0022-538X",
    publisher = "American Society for Microbiology",
    number = "15",

    }

    TY - JOUR

    T1 - Sterol regulatory element-binding protein 2 couples HIV-1 transcription to cholesterol homeostasis and T cell activation

    AU - Taylor, Harry E.

    AU - Linde, Michael E.

    AU - Khatua, Atanu K.

    AU - Popik, Waldemar

    AU - Hildreth, James E K

    PY - 2011/8

    Y1 - 2011/8

    N2 - Cholesterol plays an essential role in the life cycle of several enveloped viruses. Many of these viruses manipulate host cholesterol metabolism to facilitate their replication. HIV-1 infection of CD4 + T cells activates the sterol regulatory element-binding protein 2 (SREBP2) transcriptional program, which includes genes involved in cholesterol homeostasis. However, the role of SREBP2-dependent transcription in HIV-1 biology has not been fully examined. Here, we identify TFII-I, a gene critical for HIV-1 transcription in activated T cells, as a novel SREBP2 target gene. We found TFII-I expression increased after HIV-1 infection or activation of human primary CD4 + T cells. We show that inhibition of SREBP2 activity reduced TFII-I induction in response to these stimuli. More importantly, small interfering RNA (siRNA)-mediated gene silencing of either SREBP2 or TFII-I significantly reduced HIV-1 production in CD4 + T cells. We also found that TFII-I potentiates Tat-dependent viral gene expression, consistent with a role at the level of HIV-1 transcription. Collectively, our results demonstrate for the first time that HIV-1 transcription in T cells is linked to cholesterol homeostasis through control of TFII-I expression by SREBP2.

    AB - Cholesterol plays an essential role in the life cycle of several enveloped viruses. Many of these viruses manipulate host cholesterol metabolism to facilitate their replication. HIV-1 infection of CD4 + T cells activates the sterol regulatory element-binding protein 2 (SREBP2) transcriptional program, which includes genes involved in cholesterol homeostasis. However, the role of SREBP2-dependent transcription in HIV-1 biology has not been fully examined. Here, we identify TFII-I, a gene critical for HIV-1 transcription in activated T cells, as a novel SREBP2 target gene. We found TFII-I expression increased after HIV-1 infection or activation of human primary CD4 + T cells. We show that inhibition of SREBP2 activity reduced TFII-I induction in response to these stimuli. More importantly, small interfering RNA (siRNA)-mediated gene silencing of either SREBP2 or TFII-I significantly reduced HIV-1 production in CD4 + T cells. We also found that TFII-I potentiates Tat-dependent viral gene expression, consistent with a role at the level of HIV-1 transcription. Collectively, our results demonstrate for the first time that HIV-1 transcription in T cells is linked to cholesterol homeostasis through control of TFII-I expression by SREBP2.

    UR - http://www.scopus.com/inward/record.url?scp=79960414060&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=79960414060&partnerID=8YFLogxK

    U2 - 10.1128/JVI.00337-11

    DO - 10.1128/JVI.00337-11

    M3 - Article

    C2 - 21613400

    AN - SCOPUS:79960414060

    VL - 85

    SP - 7699

    EP - 7709

    JO - Journal of Virology

    JF - Journal of Virology

    SN - 0022-538X

    IS - 15

    ER -