Long-term inhibition of HIV-1 replication with RNA interference against cellular co-factors.

Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam, Academic Medical Center of University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Antiviral research (Impact Factor: 3.43). 01/2011; 89(1):43-53. DOI: 10.1016/j.antiviral.2010.11.005
Source: PubMed

ABSTRACT In this study we tested whether HIV-1 replication could be inhibited by stable RNAi-mediated knockdown of cellular co-factors. Cell lines capable of expressing shRNAs against 30 candidate co-factors implicated at different steps of the viral replication cycle were generated and analyzed for effects on cell viability and inhibition of HIV-1 replication. For half of these candidate co-factors we obtained knockdown cell lines that are less susceptible to virus replication. For three co-factors (ALIX, ATG16 and TRBP) the cell lines were resistant to HIV-1 replication for up to 2 months. With these cells we could test the hypothesis that HIV-1 is not able to escape from RNAi-mediated suppression of cellular co-factors, which was indeed not detected.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Described in this paper is a logic-modeling framework, based on fuzzy neural networks (FNNs) to identify causal relationships among variables. A case study is presented from the industrial construction domain to demonstrate the capability of the proposed system in finding plausible explanations of observed performance failures.
    Fuzzy Information, 2004. Processing NAFIPS '04. IEEE Annual Meeting of the; 07/2004
  • [Show abstract] [Hide abstract]
    ABSTRACT: RNA interference (RNAi) is a cellular mechanism that mediates sequence-specific gene silencing at the posttranscriptional level. RNAi can be used as an antiviral approach against human pathogens. An attractive target for RNAi therapeutics is the human immunodeficiency virus type 1 (HIV-1), and the first clinical trial using a lentiviral gene therapy was initiated in early 2008. In this chapter, we focus on some basic principles of such an RNAi-based gene therapy against HIV-1. This includes the subjects of target site selection within the viral RNA genome, the phenomenon of viral escape, and therapeutic strategies to prevent viral escape. The latter antiescape strategies include diverse combinatorial RNAi approaches that are all directed against the HIV-1 RNA genome. As an alternative strategy, we also discuss the possibilities and restrictions of targeting cellular cofactors that are essential for virus replication, but less important for cell physiology.
    Progress in molecular biology and translational science 01/2011; 102:141-63. DOI:10.1016/B978-0-12-415795-8.00001-5 · 3.11 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We discover that the slight transverse offset of a point detector results in a shift of the axial intensity response curve in a dual-axes confocal microscopy (DCM). Based on this, we propose a new dual-axes differential confocal microscopy (DDCM) with high axial resolution and long working distance, in which two point detectors are placed symmetrically about the collection axis. And a signal is obtained through the differential subtraction of two signals received simultaneously by the two point detectors. Theoretical analyses and preliminary experiments indicate that DDCM is feasible and suitable for the high precision tracing measurement of microstructures and surface contours.
    Optics Communications 01/2011; 284(1):15-19. DOI:10.1016/j.optcom.2010.08.033 · 1.54 Impact Factor