Biography
Group Leader
RNA Viruses (AIDS)
We study two major groups of viruses ; lentiviruses (retroviruses) and rotaviruses. The lentiviruses include HIV-1, HIV-2 and FIV. In all of these viruses we are interested in virus assembly, how the virus captures its RNA genome within the cell and how it uses cellular machinery to do this. The work involves structural biology, confocal microscopy and FRET as well as molecular biological techniques. We collaborate with structural biologists in Cambridge and Oxford. We also use our understanding of lentiviral RNA packaging to generate gene vectors for gene transfer and gene therapy purposes.
Publications
Moyo QM, Besser M, Lynn R Lever AML.
Persistence of imported Malaria into the UK: an epidemiological review of risk factors and at risk groups.
Clinical Infectious Diseases; 2019 69(7), 1156-1162
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.
HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation
Nature 2019 Apr;568 (7751):244-248
Skittrall JP, Ingemarsdotter CK, Gog JR, Lever AML.
A scale-free analysis of the HIV-1 genome demonstrates multiple conserved regions of structural and functional importance.
PLoS Comput Biol. 2019 Sep 23;15(9)
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.
Emergence of host-adapted Salmonella Enteritidis through rapid evolution in an immunocompromised host.
Nat Microbiol. 2016 Mar;1(3). pii: 15023. Epub 2016 Jan 25.
GautamP, Foale RD, Recino A, Zhao J,Gan S, Wallberg M, Calne R, Lever AL.
Promoter optimisation of lentiviral vectors for efficient insulin gene expression in canine mesenchymal stromal cells: potential surrogate beta cells.
Journal of Gene Medicine 2016 Oct;18(10):312-321
Fun A, Mok HP, Wills MR, Lever AM.
A highly reproducible quantitative viral outgrowth assay for the measurement of the replication-competent latent HIV-1 reservoir.
Scientific Reports 2017; 43231
Ingemarsdotter CK, Poddar S, Mercier S, Patzel V, Lever AML.
Expression of Herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) by RNA trans-splicing induces selective killing of HIV producing cells.
Molecular Therapy: Nucleic Acids 2017; 16;7:140-154
Ingemarsdotter CK, Zeng J, Long Z, Lever AML, Kenyon JC.
An RNA-binding compound that stabilizes the HIV-1 gRNA packaging signal structure and specifically blocks HIV-1 RNA encapsidation.
Retrovirology. 2018 Mar 14;15(1):25
Gog JR, Lever AML, Skittrall JP.
A new method for detecting signal regions in ordered sequences of real numbers, and application to viral genomic data.
PLoS One, 2018; 13(4)
Mok HP, Norton NJ, Hirst JC, Fun A, Bandara M, Wills MR, Lever AML.
No evidence of ongoing evolution in replication competent latent HIV-1 in a patient followed up for two years.
Sci Rep,2018; 8(1), 2639
Sithole N, Williams CA, Vaughan AM, Kenyon JC, Lever AML.
DDX17 Specifically, and independently of DDX5, controls use of the HIV A4/5 splice acceptor cluster and is essential for efficient replication of HIV.
J Mol Biol. 2018 Sep 14;430, 3111-3128
Recino A, Gan SU, Sia KC, Sawyer Y, Trendell J, Kay R, Gribble FM, Reimann F, Foale R, Notaridou M, Holmes N, Lever A, Lee KO, Nathwani A, Cooke A, Calne R, Wallberg M.
Immunosuppression overcomes insulin- and vector-specific immuneresponses that limit efficacy of AAV2/8-mediated insulin gene therapy in NOD mice.
Gene Therapy ; 2019; 26(1-2), 40-56
Meng B, Ip NCY, Abbink TEM, Kenyon JC and Lever AML.
ESCRT-II functions by linking to ESCRT-I in HIV-1 budding.
Cellular Microbiology, 2019 (in press)
Salasc F, Gludish DW, Jarvis I, Boliar S, Wills MR, Russell DG, Lever AML and Mok HP.
A novel, sensitive dual-indicator cell line for detection and quantification of inducible, replication-competent latent HIB01 from reservoir cells.
Scientific Reports, 2019 (in press)