The challenge for the immune system is that mammals do not evolve as fast as viruses. How then, in the face of this disadvantage, can the immune system hope to keep pace with viral evolution? If a protein is fragile, even small changes can render it completely unable to do its job. TRIM5α is not fragile; most random mutations increased, rather than decreased, the protein’s ability to prevent viral infection. TRIM5α can readily gain antiviral activity and, once gained, does not lose it easily during subsequent mutation.

2022-12-02: And new infections can be filmed

The early stages of the virus–cell interaction have long evaded observation by existing microscopy methods due to the rapid diffusion of virions in the extracellular space and the large 3D cellular structures involved. We present an active-feedback single-particle tracking method with simultaneous volumetric imaging of the live cell environment called 3D-TrIm to address this knowledge gap. 3D-TrIm captures the extracellular phase of the infectious cycle in what we believe is unprecedented detail. We report previously unobserved phenomena in the early stages of the virus–cell interaction, including skimming contact events at the millisecond timescale, orders of magnitude change in diffusion coefficient upon binding and cylindrical and linear diffusion modes along cellular protrusions. We demonstrate how this method can move single-particle tracking from simple monolayer culture toward more tissue-like conditions by tracking single virions in tightly packed epithelial cells. This multiresolution method presents opportunities for capturing fast, 3D processes in biological systems.