Abstract: 

Enveloped viruses consist of large variety of viral families, many of which contain highly threatening human pathogens such as HIV, influenza virus, Ebola virus and Zika virus. The genome of an enveloped virus is wrapped by a lipid bilayer, which in turn is coated by viral glycoproteins (GP). These proteins mediate viral binding to the host cell, viral entry and membrane fusion. Understanding the infection mechanism requires structural insights into the GP. However, due to the pleomorphicity of enveloped viruses, solving the GP structure in vivo remains challenging. Here we performed 3D reconstruction of two viruses, namely Tula virus (TULV) from the Bunyaviridae family and Lassa virus (LASV) from the Arenaviridae family, at ~15-Å resolution using cryo-electron tomography and subtomogram averaging. In the TULV work, the EM reconstruction of the GP facilitates fitting of the crystal structures of its Gn and Gc subunits, providing a molecular level interpretation of the antigenic hantaviral surface. In the LASV work, we solved the GP structures at various pH’s and in the presence of a functional cellular receptor, human LAMP-1. This work revealed specific structural rearrangements in the GP during endocytosis of the virus, providing a molecular level rationale for this important stage of host cell infection.