Structural basis of host protein hijacking in human T-cell leukemia virus integration

• DOI: 10.1038/s41467-020-16963-6
• Publication Date: 2020-06-19T10:03:27Z
• Authors: Veer Bhatt; Ke Shi; Daniel J. Salamango; Nicholas H. Moeller; Krishan K. Pandey; Sibes Bera; Heather O. Bohl; Fredy Kurniawan; Kayo Orellana; Wei Zhang; Duane P. Grandgenett; Reuben S. Harris; Anna C. Sundborge...; Hideki Aihara
• Keywords: Models, Molecular; Human T-lymphotropic virus 1; 0303 health sciences; Integrases; Science; Virus Integration; Q; Cryoelectron Microscopy; Article; 3. Good health; Viral Proteins; 03 medical and health sciences; HEK293 Cells; DNA, Viral; Host-Pathogen Interactions; Humans; Point Mutation; Protein Phosphatase 2; Protein Binding

Abstract Integration of the reverse-transcribed viral DNA into host chromosomes is a critical step in life-cycle retroviruses, including an oncogenic delta(δ)-retrovirus human T-cell leukemia virus type-1 (HTLV-1). Retroviral integrase forms higher order nucleoprotein assembly (intasome) to catalyze integration reaction, which roles factors remain poorly understood. Here, we use cryo-electron microscopy visualize HTLV-1 intasome at 3.7-Å resolution. The structure together with functional analyses reveal that B56γ (B’γ) subunit essential enzyme, protein phosphatase 2 A (PP2A), repurposed as integral component mediate integration. Our studies key host-virus interaction underlying replication important pathogen and highlight divergent strategies retroviruses.