Within you, without you: HIV-1 Rev and RNA export

Center for Biologics Evaluation and Research, Food and Drug Administration, USA.
Retrovirology (Impact Factor: 4.77). 02/2004; 1:35. DOI: 10.1186/1742-4690-1-35
Source: PubMed

ABSTRACT Nucleo-cytoplasmic transport of RNA is one of many cellular pathways whose illumination has progressed hand in hand with understanding of retroviral mechanisms. A recent paper in Cell reports the involvement of an RNA helicase in the pathway by which HIV exports partially spliced and unspliced RNA out of the nucleus. This suggests the ubiquity of RNA helicases in RNA export from the nucleus, and has novel mechanistic implications.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Current treatment of HIV/AIDS consists of a combination of three to five agents targeting different viral proteins, i.e. the reverse transcriptase, protease, integrase and envelope, and aims to suppress viral replication below detectable levels. This "highly active antiretroviral therapy" (HAART) has brought an enormous benefit for life expectancy and quality in HIV-1-infected individuals, at least in industrialized countries. However, significant limitations with regard to efficiency, drug resistance, side effect and costs still exist. Recent data suggest that cellular factors also represent useful targets for therapy. Here, we summarize findings from several genome-wide screens that identified a large number of cellular factors exploited by HIV-1 at each step of its life cycle. Furthermore, we discuss the evidence that humans are equipped with powerful intrinsic defense mechanisms against retroviruses but that HIV-1 has evolved elaborate ways to counteract or evade them. Preventing the use of host cell proteins obligatory for viral replication or strengthening the cellular defense mechanisms may help to reduce viral replication to harmless levels. A better understanding of the host factors that promote or restrict HIV-1 replication may thus lead to the development of novel therapeutics against HIV/AIDS.
    Biochimica et Biophysica Acta 12/2009; 1802(3):313-21. DOI:10.1016/j.bbadis.2009.12.003 · 4.66 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: CNS associated cells are permissive to HIV-1 infection, but poor in virus production due to attenuated Rev activity. The temporal and the spatial distribution of Rev in human astrocyte 1321N1 and glioblastoma GO-G-CCM were monitored for explaining the reduced Rev activity and low viral production during HIV-1 infection. Rev remained localized to the nuclei of these cells upon infection, attenuating its export activity, as manifested by low copy number of RRE-containing viral-mRNA in the cytoplasm of these cells. In contrast to infection, when Rev alone was transiently expressed, it localized in the cytoplasm of 1321N1. The localization changed to the nucleus when Rev was expressed in the presence of other viral proteins through pro-viral DNA pNL4-3. This study, for the first time, revealed the impact of other HIV-1 proteins apart from host factors in regulating the subcellular localization of Rev in astrocytes and hence the fate of HIV-1 infection in these cells.
    PLoS ONE 09/2013; 8(9):e72905. DOI:10.1371/journal.pone.0072905 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Productive HIV replication in the CNS occurs very early after infection, yet HIV-associated cognitive disorders do not typically manifest until the development of AIDS, suggesting that mechanisms exist in the CNS to control HIV replication and associated virus-induced pathological changes during the acute and asymptomatic stages of disease. Using an established SIV/macaque model of HIV dementia, we recently demonstrated that the mechanisms regulating virus replication in the brain at these stages involve the production of IFNβ, which induces the truncated, dominant-negative isoform of C/EBPβ, also referred to as LIP (liver-enriched transcriptional inhibitory protein). Alternative translation of C/EBPβ mRNA and increased production of LIP can be mediated by CUGBP1 (CUG-repeat RNA-binding protein 1). Because IFNβ induces the inhibitory C/EBPβ in macrophages, we considered the possibility that IFNβ signaling regulates the activity of CUGBP1, resulting in increased expression of LIP and suppression of SIV replication. In this study, we report that IFNβ induces LIP and suppresses active SIV replication in primary macrophages from rhesus macaques. Further, we demonstrate that IFNβ induces the phosphorylation of CUGBP1 and the formation of CUGBP1-C/EBPβ mRNA complexes in the human monocytic U937 cell line. Finally, we demonstrate that CUGBP1 is not only required for IFNβ-mediated induction of LIP but also for IFNβ-mediated suppression of SIV replication. These results suggest that CUGBP1 is a previously unrecognized downstream effector of IFNβ signaling in primary macrophages that likely plays a pivotal role in innate immune responses that control acute HIV/SIV replication in the brain.
    The Journal of Immunology 12/2007; 179(11):7262-7269. · 5.36 Impact Factor


Available from