title: HIV-1 induced nuclear factor I-B (NF-IB) expression negatively regulates HIV-1 replication through interaction with the long terminal repeat region.
abstract: BACKGROUND
  Retroviruses rely on host factors for cell entry, replication, transcription, and other major steps during their life cycle. Human Immunodeficiency Virus-1 (HIV-1) is well known for utilizing a plethora of strategies to evade the host immune response, including the establishment of latent infection within a subpopulation of susceptible cells. HIV-1 also manipulates cellular factors in latently infected cells and persists for long periods of time, despite the presence of successful highly active antiretroviral therapy (HAART).
  
  
  RESULTS
  In this study we demonstrate that Nuclear Factor-IB (NF-IB) is induced during HIV-1 infection and its expression negatively impacts viral replication. During HIV-1 infection in peripheral blood mononuclear cells (PBMCs), and the T cell line, Jurkat or during induction of virus replication in latently infected cells, ACH2 and J1.1, we observed a time-dependent alteration in NF-IB expression pattern that correlated with HIV-1 viral expression. Using the Chip assay, we observed an association of NF-IB with the long terminal repeat region of HIV-1 (LTR) (-386 to -453 nt), and this association negatively correlated with HIV-1 transcription. Furthermore, knock-down of NF-IB levels in J1.1 cells resulted in an increase of HIV-1 levels. Knock-down of NF-IB levels in J-Lat-Tat-GFP (A1), (a Jurkat cell GFP reporter model for latent HIV-1 infection) resulted in an increase in GFP levels, indicating a potential negative regulatory role of NF-IB in HIV-1 replication.
  
  
  CONCLUSIONS
  Overall, our results suggest that NF-IB may play a role in intrinsic antiretroviral defenses against HIV-1. These observations may offer new insights into the correlation of the latently infected host cell types and HIV-1, and help to define new therapeutic approaches for triggering the switch from latency to active replication thereby eliminating HIV-1 latent infection.
authors: Laboratory of Molecular Virology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA. saivikram.vemula@fda.hhs.gov.
authors: Sai Vikram
authors: SV
authors: Vemula
authors: Laboratory of Molecular Virology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA. veerasamy.ravichandra@nih.gov.
authors: Ravichandran
authors: R
authors: Veerasamy
authors: Laboratory of Molecular Virology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA. viswanath.ragupathy@fda.hhs.gov.
authors: Viswanath
authors: V
authors: Ragupathy
authors: Laboratory of Molecular Virology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA. santanu.biswas@fda.hhs.gov.
authors: Santanu
authors: S
authors: Biswas
authors: Laboratory of Molecular Virology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA. krishnakumar.devadas@fda.hhs.gov.
authors: Krishnakumar
authors: K
authors: Devadas
authors: Laboratory of Molecular Virology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA. Indira.hewlett@fda.hhs.gov.
authors: Indira
authors: I
authors: Hewlett
mesh_terms: D002460:Cell Line; D015870:Gene Expression; D005786:Gene Expression Regulation; D020868:Gene Silencing; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D051839:NFI Transcription Factors / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D014775:Virus Activation; D017735:Virus Latency; D014779:Virus Replication
chemical_list: D051839:NFI Transcription Factors; C110754:NFIB protein, human