Structure and function of the assembled protein network of HIV-1 and its changes upon maturation

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Morphogenesis of infectious HIV-1 and other retroviruses involves assembly of the Gag polyprotein lattice, particle release of the immature, non-infectious virus consisting largely of uncleaved Gag polyproteins from the plasma membrane and maturation to the infectious virus with its characteristic cone-shaped morphology following Gag proteolysis. In our joint project with John Briggs (now LMB Cambridge), we have determined the high resolution structure of the CA (capsid) domain in the immature Gag lattice, have identified the central switch controlling architectural maturation of the capsid and have determined the CA lattice structure in the mature capsid for both HIV-1 and MLV. Based on these results, we now plan in our continued collaboration with John Briggs to identify and structurally characterize HIV-1 maturation intermediates, to determine the structure and organization of the MA (matrix) lattice and its changes during maturation as well as its potential association with the viral glycoproteins and to characterize changes in capsid architecture during reverse transcription of the genome and/or upon host factor binding. This project continues our ongoing collaboration along the course of viral replication steps and extends this work to structural analysis of other essential virion components and their changes during the course of maturation to the infectious virion.