Research
We are interested in aspects of the molecular and structural biology of HIV. We are seeking new ways to combat this virus and to eradicate it. We work on how RNA viruses such as HIV package their genetic material using new RNA modelling methods like SHAPE to identify important RNA structures involved in genome encapsidation, and how viruses select their own RNA from the cell so specifically and ways to inhibit this. We study HIV latency and ways in which we can reawake latent viruses on the path to trying to eradicate it. We are using novel techniques including trans splicing to approach this.
Selected References
Antiretroviral therapy alone versus antiretroviral therapy with a kick and kill approach, on measures of the HIV reservoir in participants with recent HIV infection (the RIVER trial): a phase 2, randomised trial.Fidler S, Stöhr W, Pace M, Dorrel L, Lever A, Pett S, Kinloch-de Loes S, Fox J, Clarke A, Nelson M, Thornhill J, Khan M, Fun A, Bandara M, Kelly D, Kopycinski J, Hanke T, Yang H, Bennett R, Johnson M, Howell B, Barnard R, Wu G, Kaye S, Wills M, Babiker A, Frater J on behalf of the RIVER trial study group.The Lancet, 2020
HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation. Gupta RK, Abdul-Jawad S, McCoy LE, Mok HP, Salgado DPM, Martinez-Picado J, Nijhuis M, Wensing AMJ, Lee H, Grant P, Nastouli E, Lambert J, Pace M, Salasc F, Monit C, Innes, Mui L, Waters L, Frater J, Lever AML, Edwards SG, Gabriel IH, Olavarria E. Nature 2019 Apr;568 (7751):244-248
A new method for detecting signal regions in ordered sequences of real numbers, and application to viral genomic data. Gog JR, Lever AML, Skittrall JP PLoS One, 2018; 13(4)
No evidence of ongoing evolution in replication competent latent HIV-1 in a patient followed up for two years. Mok HP, Norton NJ, Hirst JC, Fun A, Bandara M, Wills MR, Lever AML Sci Rep,2018; 8(1), 2639
DDX17 Specifically, and independently of DDX5, controls use of the HIV A4/5 splice acceptor cluster and is essential for efficient replication of HIV. Sithole N, Williams CA, Vaughan AM, Kenyon JC, Lever AML J Mol Biol. 2018 Sep 14;430, 3111-3128
Persistence of imported Malaria into the UK: an epidemiological review of risk factors and at risk groups Moyo QM, Besser M, Lynn R Lever AML Clinical Infectious Diseases
Expression of Herpes Simplex Virus Thymidine Kinase/Ganciclovir by RNA Trans-Splicing Induces Selective Killing of HIV-Producing Cells. Ingemarsdotter CK, Poddar S, Mercier S, Patzel V, Lever AML. Mol Ther Nucleic Acids. 2017 Jun 16;7:140-154.
A highly reproducible quantitative viral outgrowth assay for the measurement of the replication-competent latent HIV-1 reservoir. Fun A, Mok HP, Wills MR, Lever AM. Sci Rep. 2017 Feb 24;7:43231
Innovations in the quantitative virus outgrowth assay and its use in clinical trials. Norton NJ, Fun A, Bandara M, Wills MR, Mok HP, Lever AML. Retrovirology. 2017 Dec 21;14(1):58.
Coordination of Genomic RNA Packaging with Viral Assembly in HIV-1. Hellmund C, Lever AM. Viruses. 2016 Jul 14;8(7
Emergence of host-adapted Salmonella Enteritidis through rapid evolution in an immunocompromised host. Klemm EJ, Gkrania-Klotsas E, Hadfield J, Forbester JL, Harris SR, Hale C, Heath JN, Wileman T, Clare S, Kane L, Goulding D, Otto TD, Kay S, Doffinger R, Cooke FJ, Carmichael A, Lever AM, Parkhill J, MacLennan CA, Kumararatne D, Dougan G, Kingsley RA. Nat Microbiol. 2016 Mar;1(3). pii: 15023.
Promoter optimisation of lentiviral vectors for efficient insulin gene expression in canine mesenchymal stromal cells: potential surrogate beta cells. Gautam P, Recino A, Foale RD, Zhao J, Gan SU, Wallberg M, Calne R, Lever AM. J Gene Med. 2016 Oct;18(10):312-321.
Coordination of Genomic RNA Packaging with Viral Assembly in HIV-1. Hellmund C, Lever AM. Viruses. 2016 Jul 14;8(7
Characterizing 3D RNA structure by single molecule FRET. Stephenson JD, Kenyon JC, Symmons MF, Lever AM. Methods. 2016 Jul 1;103:57-67.
A novel combined RNA-protein interaction analysis distinguishes HIV-1 Gag protein binding sites from structural change in the viral RNA leader. Kenyon JC, Prestwood LJ, Lever AM. Sci Rep. 2015 Oct 9;5:14369