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Professor Andrew Lever

Departments

Department of Medicine:
Professor of Infectious Diseases

Research Interests

We focus on the structural analysis of packaging signals in mammalian retroviruses and rotaviruses. We have identified packaging signals in HIV-1, HIV-2 and SIV and have two and three-dimensional structure of varying parts of these. We also use single molecule FRET and new SHAPE technology to derive three dimensional structures of these RNAs and determine RNA/RNA and RNA protein interactions. We were the first to demonstrate cotranslational packaging in HIV-2, since confirmed in HIV-1. We also identified critical differences in RNA packaging between the closely related HIV-1 and HIV-2, both of which are causative agents of AIDS. We have recently been awarded a Milstein grant from the MRC developing an assay for a high throughput screen to look for novel therapies against HIV targeting the packaging process. In a recent collaboration with Dept Surgery we've been trying to deliver genes which optimise organ transplantation and reduce allograft rejection.

Keywords

rotavirus ; cell processes ; RNA structure ; retrovirus ; RNA packaging

Topics

  • immunodeficiency

Key Publications

Wei B, Han L, Abbink TEM, Elisabetta G, Lim D, Thaker R, Gao W, Wang J, Lever A, Jolly C, Wang H, Rudd CE (2013) Immune adaptor ADAP in T cells regulates HIV-1 transcription and cell-cell viral spread via different co-receptors. Retrovirol. 10, 101. PMID: 24047317. 

Bell NM, L'Hernault A, Murat P, Richards JE, Lever AM, Balasubramanian S. Targeting RNA-protein interactions within the human immunodeficiency virus type 1 lifecycle. Biochemistry. 2013 Dec 23;52(51):9269-74. 

Bell NM, Kenyon JC, BalasubramanianS, and Lever, AML Comparative Structural Effects of HIV-1 Gag and Nucleocapsid Proteins in Binding to and Unwinding of the Viral RNA Packaging Signal Biochemistry, 2012, 51 (15): 3162–3169

Kenyon JC, Tanner SJ, Legiewicz M, Phillip PS, Rizvi TA, Le Grice SFJ, Lever AML. SHAPE Analysis of the FIV Leader RNA reveals a structural switch potentially controlling Viral Packaging and Genome Dimerization Nucleic Acids Res. 2011; 39(15):6692-6704

Zhao J, Sinclair J, Houghton J, Bolton E, Bradley A, Lever A, Cytomegalovirus beta2.7 RNA transcript protects endothelial cells against apoptosis during ischemia/reperfusion injury, J Heart Lung Transplant 2010 29:342–5

Li W, Manktelow E, von Kirchbach JC, Gog JR, Desselberger U, Lever AM, “Genomic analysis of codon, sequence and structural conservation with selective biochemical-structure mapping reveals highly conserved and dynamic structures in rotavirus RNAs with potential cis-acting functions”, Nucleic Acids Res 2010 38(21):7718–7735

Groom HC, Anderson EC, Dangerfield JA, Lever AM, (2009) Rev regulates translation of human immunodeficiency virus type 1 RNAs Journal of General Virology 90: 1141–1147

Mok, H P, Javed S, Lever AML , Stable gene expression occurs from a minority of integrated HIV-1 based vectors: transcriptional silencing is present in the majority, Gene Therapy 2007 14:741–751