Three-dimensional insights into human enveloped viruses in vitro and in situ

Abstract

Viruses can be enveloped or non-enveloped, and require a host cell to replicate and package their genomes into new virions to infect new cells. To accomplish this task, viruses hijack the host-cell machinery to facilitate their replication by subverting and manipulating normal host cell function. Enveloped viruses can have severe consequences for human health, causing various diseases such as acquired immunodeficiency syndrome (AIDS), seasonal influenza, COVID-19, and Ebola virus disease. The complex arrangement and pleomorphic architecture of many enveloped viruses pose a challenge for the more widely used structural biology techniques, such as X-ray crystallography. Cryo-electron tomography (cryo-ET), however, is a particularly well-suited tool for overcoming the limitations associated with visualizing the irregular shapes and morphology enveloped viruses possess at macromolecular resolution. The purpose of this review is to explore the latest structural insights that cryo-ET has revealed about enveloped viruses, with particular attention given to their architectures, mechanisms of entry, replication, assembly, maturation and egress during infection. Cryo-ET is unique in its ability to visualize cellular landscapes at 3–5 nanometer resolution. Therefore, it is the most suited technique to study asymmetric elements and structural rearrangements of enveloped viruses during infection in their native cellular context.

A Frame-by-Frame Glance at Membrane Fusion Mechanisms: From Viral Infections to Fertilization

“…Another important biological event that requires membrane fusion is enveloped virus entry/infection [63]. Enveloped viruses are enclosed in a phospholipid bilayer that originates from the cellular membranes of previously infected cells; the viral membranes form as the nascent virions bud off the host cell surface and are released into the extracellular environment.…”

“…From there, the virions must find another host cell and begin the process anew via viral entry, a membrane fusion event that proceeds in the opposite direction of the viral release process. In this way, viral fusion and viral release are two faces of the same biological coin [63].…”

“…Enveloped viruses cause some of the most common and impactful diseases of the modern era, including COVID-19, acquired immunodeficiency syndrome (AIDS), and seasonal influenza [63]. Parallel to their heterogeneity in cellular tropism, symptoms, and disease progression, enveloped viruses demonstrate vast heterogeneity in their virion structure, including their fusion proteins and subsequent processes.…”