Cellular proteins interacting with curved HIV-1 capsid lattices

Early events of HIV-1 lifecycle, such as post-entry virus trafficking, uncoating and nuclear import, remain poorly understood due to limited information about virus-host interactions. We used a multidisciplinary approach. First, a mass spectrometry (MS)-based proteomics methodology enabled us to identify cellular proteins that specifically bind to 3-dimensional curved hexameric capsid lattices closely mimicking the assembled HIV-1 core. We then employed virology, live cell imaging, CRISPR gene knockout, x-ray crystallography, and biochemistry to demonstrate that Sec24C (a component of the COPII complex) is the first example of a cytoplasmic protein that utilizes an FG containing motif to directly and specifically bind the curved hexameric HIV-1 capsid lattices.