Cell and Molecular Biology Monday Seminar Series: Marina Lusic (Universität Heidelberg) - Nuclear landscape of HIV-1 integration and transcription

  • Title:  Nuclear landscape of HIV-1 integration and transcription
  • When:  Monday 9 October 2017
  • Time: 12.05 pm
  • Location:  Daniel Rutherford Building, G.27, Lecture Theatre 1, King's Buildings
  • Speaker:  Department of Infectious Diseases, Virology, Universität Heidelberg
  • Host: Eric Schirmer

Summary

HIV-1 integrates into the cellular genome to complete its life cycle. Intriguingly, the position of theintegrated virus has functional consequences for viral transcription, which usually follows integration. Whencertain regions of the cellular genome are targeted, viral transcription becomes attenuated while host cellsundergo proliferation resulting in a persistent infection1.Integration of the viral genome into host DNA depends on the enzymatic activity of HIV-1 integrase andinvolves different cellular factors, which influence the selection of integration sites. Integration canhypothetically occur throughout the genome; nevertheless it is not a random process. HIV-1 integrase prefersa specific sequence at the end of the viral DNA, whereas at the chromatin level integration site selection isinfluenced by three major determinants: sequence specificity, chromatin structure and cellular tetheringfactors1.The role of nuclear architecture in HIV-1 life cycle emerged as essential for HIV-1 integration andtranscription 2,3. My laboratory aims at understanding the nuclear organization of primary human T cells,natural targets of HIV-1. We have previously shown that HIV integration occurs in the outer shell of thenucleus in close correspondence with the nuclear pore, where the proviral DNA associates with severalnucleoporins3. This region contains a series of cellular genes, characterized by the presence of activetranscription chromatin marks, which are preferentially targeted by the virus. In contrast, the virus stronglydisfavors the heterochromatic regions in the nuclear lamin-associated domains and other transcriptionallyactive regions located centrally in the nucleus.We are currently working in further defining the properties of the genes into which HIV-1 recurrentlyintegrates: how are these genes organized in the 3D nuclear space, what are their chromatin features and howis their transcriptional fate regulated by both activation state of the cell and by the presence of the virus.

  1. Lusic, M. & Siliciano, R. F. Nuclear landscape of HIV-1 infection and integration. Nature reviews.Microbiology 15, 69-82, doi:10.1038/nrmicro.2016.162 (2017).
  2. Lusic, M. et al. Proximity to PML nuclear bodies regulates HIV-1 latency in CD4+ T cells. Cell host &microbe 13, 665-677, doi:10.1016/j.chom.2013.05.006 (2013).
  3. Marini, B. et al. Nuclear architecture dictates HIV-1 integration site selection. Nature 521, 227-231,doi:10.1038/nature14226 (2015).
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