National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
米国
引用
ジャーナル: Nat Commun / 年: 2020 タイトル: Structural basis of host protein hijacking in human T-cell leukemia virus integration. 著者: 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 ...著者: 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 Sundborger-Lunna / Hideki Aihara / 要旨: 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 ...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.