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