Structural basis for spumavirus GAG tethering to chromatin

Significance Spumaviruses are being developed as vectors for gene-therapy applications, but how these retroviruses select genomic locations for integration remains unknown. Here we use X-ray crystallography to visualize the interaction between the spumaviral GAG protein and a nucleosome. We show that this interaction is essential for the observed distribution of spumavirus integration sites in various human cell types. Thus, despite stark differences in the mechanistic details of spumavirus and orthoretrovirus replication strategies, both retroviral subfamilies depend on their structural proteins to locate optimal integration sites.