Abstract
Human immunodeficiency virus (HIV) carries out DNA synthesis inside the viral capsid. Electrostatic channels in the capsid import the necessary nucleotides. Channel activity and capsid uncoating for genome release are regulated by host cofactors, as well as by capsid binding drugs that potently inhibit infection, but mechanistic details remain unclear. Here we will investigate the allosteric changes that occur in the capsid on cofactor binding using solution state NMR methods. Hypotheses suggested by NMR will subsequently be tested in cellular infection experiments. Comparison of different HIV strains in NMR studies and infection assays will facilitate a multidisciplinary comparative approach.
References
HIV-1 uses dynamic capsid pores to import nucleotides and fuel encapsidated DNA synthesis. Jacques DA, McEwan WA, Hilditch L, Price AJ, Towers GJ, James LC. Nature. 2016 Aug 18;536(7616):349-53.
HIV-1 evades innate immune recognition through specific cofactor recruitment. Rasaiyaah J, Tan CP, Fletcher AJ, Price AJ, Blondeau C, Hilditch L, Jacques DA, Selwood DL, James LC, Noursadeghi M, Towers GJ. Nature. 2013 Nov 21;503(7476):402-405.