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SUMMARY:"Catch me if you can: understanding innate immune  evasion by HIV 
 and how to drug it" - Professor Greg Towers (University College London )
DTSTART;VALUE=DATE-TIME:20180921T110000
DTEND;VALUE=DATE-TIME:20180921T120000
UID:https://talks.ox.ac.uk/talks/id/e124d53d-00a8-4b36-948c-e1744cc5afe5/
DESCRIPTION:Cells are very hostile places for viruses. The intracellular i
 nnate immune system typically protects cells from infection and successful
  viruses must evade\, avoid or antagonise innate immune defenses in order 
 to infect their host. The host-virus interactions involved in innate evasi
 on dictate species and cell type specific replication. A key feature of in
 nate immune sensing is detection of foreign nucleic acids.  For example\, 
 cytoplasmic DNA is sensed as a danger signal leading to production of infl
 ammatory cytokines and cell death. Our central research question is: How d
 o retroviruses infect cells without activating innate immune defenses when
  they synthesise viral DNA in the \ncytoplasm? We hypothesise that HIV DNA
  synthesis is contained within the protective shell of the viral capsid\, 
 which protects it from nucleases and DNA sensors\, in a process we call cl
 oaking. We have discovered that the capsid hexamers form channels through 
 which we propose nucleotides are transported to fuel encapsidated DNA synt
 hesis. We find that breaking cofactor interactions by depleting cofactors\
 , or by mutation of CA cofactor binding sites\, causes virus to trigger in
 nate immune sensors and suppresses replication in innate immune competent 
 cells. We have also compared the capsids of pandemic HIV isolates and thei
 r less successful non-pandemic counterparts. We find that non-pandemic HIV
  are much less effective at innate evasion and have quite different capsid
  structures. We propose that adapting to evade innate sensing in myeloid c
 ells is a key feature driving HIV-1 pandemicity. We have used this new kno
 wledge to develop capsid and host cofactor-targeting inhibitors\, which un
 cloak virus and cause innate immune activation\, as a novel paradigm for p
 rophylaxis and treatment of viral infection.\n\nSpeakers:\nProfessor Greg 
 Towers (University College London )
LOCATION:Wellcome Trust Centre for Human Genetics (Meeting rooms A & B)\, 
 Headington OX3 7BN
TZID:Europe/London
URL:https://talks.ox.ac.uk/talks/id/e124d53d-00a8-4b36-948c-e1744cc5afe5/
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DESCRIPTION:Talk:"Catch me if you can: understanding innate immune  evasio
 n by HIV and how to drug it" - Professor Greg Towers (University College L
 ondon )
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