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HOST FACTORS THAT FACILITATE AND RESTRICT HIV-1 REPLICATION

Objective

The efficient replication and spread of the Human Immunodeficiency Virus type 1 (HIV-1), the causative agent of the AIDS pandemic, requires that it parasitize an array of cellular proteins, many of which are unknown or uncharacterized, to facilitate its replication. In addition the virus must also defeat or subvert the human immune defences arrayed against it. Some of these immune defences, the innate retroviral restriction factors, have the capacity not only to directly interfere with the replication of the virus, but potentially to relay the information of its presence to activate a wider immune response – so called innate immune ‘sensing’. Molecular characterization of these processes for in vitro and in vivo replication of HIV-1 are essential for our understanding of the pathogenesis of HIV/AIDS. Additionally, it will provide strategies for the development of novel therapeutics for HIV treatment, and also potentially provide new paradigms that are applicable to other pathogenic mammalian viruses. To fill these gaps in our understanding this application seeks 5 years of ERC Starter Grant funding to explore two major research aims. Firstly we propose to characterize the interactions of retroviral restriction factors with the wider systemic immune response focusing on Tetherin/CD317/BST2 as a model system. In particular we will build on preliminary data suggesting that Tetherin can act as a general “pattern recognition molecule” for sensing assembling enveloped viruses by: A) transducing a proinflammatory signal and B) targeting nascent viral particles for antigen processing and presentation. Secondly we will apply novel genetic methods based on a haploid human cell line to identify, isolate and characterize human proteins that are required for early post-entry events in HIV replication or the function of the viral accessory protein Vpu.

Field of science

  • /medical and health sciences/health sciences/public and environmental health/epidemics prevention/immunisation
  • /natural sciences/biological sciences/microbiology/virology
  • /medical and health sciences/health sciences/infectious disease/RNA virus/hiv
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /natural sciences/computer and information sciences/artificial intelligence/pattern recognition

Call for proposal

ERC-2011-StG_20101109
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

KING'S COLLEGE LONDON
Address
Strand
WC2R 2LS London
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 500 000
Principal investigator
Stuart John Douglas Neil (Dr.)
Administrative Contact
Paul Labbett (Dr.)

Beneficiaries (1)

KING'S COLLEGE LONDON
United Kingdom
EU contribution
€ 1 500 000
Address
Strand
WC2R 2LS London
Activity type
Higher or Secondary Education Establishments
Principal investigator
Stuart John Douglas Neil (Dr.)
Administrative Contact
Paul Labbett (Dr.)