# Visualizing host-virus interactions at high resolutions in situ

## TL;DR

This paper presents new cryo-EM techniques to visualize virus-cell interactions and protein synthesis at high resolution in their natural environments.

## Contribution

The study introduces an advanced in situ cryo-EM method combining automated FIB milling to achieve unprecedented structural detail in native biological contexts.

## Key findings

- A 2.19 Å resolution structure of the human 80S ribosome was resolved using the new method.
- 23 distinct functional states of the ribosome were uncovered.
- High-resolution insights were obtained from cells treated with homoharringtonine and cycloheximide.

## Abstract

Understanding virus and macromolecular structures in their natural viral and cellular environments is key to advancing biology and improving health. Here, I highlight recent advancements in in situ single-particle cryo-electron microscopy (cryo-EM), which has enabled us to observe how HIV-1 capsids interact with antiviral compounds directly within the virus’s native environment. Additionally, we showcase the unprecedented detail of protein synthesis in human cells using a method that combines automated cryo-focused ion beam (FIB) milling with in situ single-particle cryo-EM. With this approach, we resolved a 2.19 Å resolution structure of the human 80S ribosome and uncovered 23 distinct functional states. We also obtained high-resolution structural insights from cells treated with the anti-tumor drug homoharringtonine and the inhibitor cycloheximide. Collectively, our work represents a significant advancement in structural studies within natural contexts, highlighting a powerful tool to investigate virus infection and basic biology.