Kate Bishop

Retroviral Replication Laboratory

Retroviruses cause severe diseases, including immunodeficiency and cancer. The human immunodeficiency virus (HIV) is the most widely known retrovirus due to its impact on human health. The latest figures (WHO/UNAIDS 2015) report that 36 million people globally are living with HIV/AIDS.

Innovative therapeutics for retroviral diseases will hopefully arise from a better understanding of how retroviruses reproduce in the cell, how they interact with host cell factors and how they subvert the host innate and adaptive immune systems. The early stages of the retroviral life cycle are particularly attractive therapeutic targets, with several anti-retroviral drugs and cellular anti-viral factors inhibiting these steps. However, numerous events that occur during these stages are still poorly understood. The three main projects in our laboratory aim to characterise the molecular events that occur once a retrovirus has entered a cell in order to fully understand retroviral replication and provide potential ways in which to manipulate these processes for the benefit of human health.

 

The life cycle of a retrovirus

The retroviral life cycle is arbitrarily divided into two phases, early and late. The stages in each phase are shown above. Interactions between viral and host cell factors occur at every stage of the viral life cycle, although many are still poorly understood. Identifying and understanding these interactions are key to developing new treatments to combat retroviral diseases. The steps inhibited by three retroviral restriction factors TRIM5alpha, APOBEC3G and Fv1 are also indicated. (RTC, reverse transcription complex; PIC, pre-integration complex) (Click to view larger image)

 

Selected publications

Cosnefroy, O; Murray, PJ and Bishop, KN (2016) HIV-1 capsid uncoating initiates after the first strand transfer of reverse transcription. Retrovirology 13, 58 

Arnold, LH; Groom, HCT; Kunzelmann, S; Schwefel, D; Caswell, SJ; Ordonez, P; Mann, MC; Rueschenbaum, S; Goldstone, DC; Pennell, S; Howell, SA; Stoye, JP; Webb, M; Taylor, IA and Bishop, KN (2015) Phospho-dependent regulation of SAMHD1 oligomerisation couples catalysis and restriction. PLoS Pathogens 11, e1005194 

Schwefel, D; Boucherit, VC; Christodoulou, E; Walker, PA; Stoye, JP; Bishop, KN and Taylor, IA (2015) Molecular determinants for recognition of divergent SAMHD1 proteins by the lentiviral accessory protein Vpx. Cell Host & Microbe 17, 489-499 

Wight DJ, Boucherit VC, Wanaguru M, Elis E, Hirst EMA, Li W, Ehrlich M, Bacharach E and Bishop KN. (2014) The N-terminus of murine leukaemia virus p12 protein is required for mature core stability. PLoS Pathogens 10, e1004474

Schwefel, D; Groom, HCT; Boucherit, VC; Christodoulou, E; Walker, PA; Stoye, JP; Bishop, KN and Taylor, IA (2014) Structural basis of lentiviral subversion of a cellular protein degradation pathway. Nature 505, 234-238

Wight DJ, Boucherit VC, Nader M, Allen DJ, Taylor IA and Bishop KN. (2012) The Gammaretroviral p12 Protein has Multiple Domains that Function During the Early Stages of Replication. Retrovirology 9, 83

Kate Bishop

kate.bishop@crick.ac.uk
+44 (0)20 379 62431

  • Qualifications and history
  • 1998-2001: PhD in Virology, MRC-NIMR affiliated to UCL, London, UK
  • 2002-2004: Post doctoral researcher, King's College London, UK
  • 2004-2008: Royal Society Dorothy Hodgkin Fellow, King's College London, UK
  • 2008-2014: Wellcome Trust Career Development Fellow, MRC-NIMR, London, UK
  • Since 2008: Group Leader, Medical Research Council National Institute for Medical Research, London, UK
  • 2015 Group Leader, the Francis Crick Institute, London, UK