Structure and arrangement of viral proteins in HIV, Marburg and Influenza viruses

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The formation of virus particles is driven by the assembly of viral structural proteins into regular lattices. Nevertheless, for many enveloped viruses, including human pathogens such as Human immunodeficiency virus (HIV), Marburg and Influenza viruses, this regular assembly leads to the production of virus particles that are highly heterogenous in size and shape. These viruses use assembly mechanisms which incorporate flexibility and variability to allow robust assembly and envelopment in the heterogeneous cellular environment. This structural heterogeneity has frustrated attempts to study the arrangement of the viral structural proteins. As a result it is not clear how the domains of the virus structural proteins are arranged within the repeating lattice, or how the lattice is arranged to form a whole virus particle. Here we propose to apply state of the art cryo-electron tomography and sub-tomogram averaging approaches to HIV, Marburg and Influenza viruses. In each case, we will solve the structure of the local viral protein lattice, and map the position of every individual unit cell of the protein lattice in complete virus particles. In the case of Marburg virus, we will also do this for particles budding from cells. These experiments will answer specific structural questions about the individual viruses, and also reveal general principles as to how these viruses combine regularity and heterogeneity to assemble and envelope infectious particles.