TY - JOUR
T1 - Structural basis of host protein hijacking in human T-cell leukemia virus integration
AU - Bhatt, Veer
AU - Shi, Ke
AU - Salamango, Daniel J.
AU - Moeller, Nicholas H.
AU - Pandey, Krishan K.
AU - Bera, Sibes
AU - Bohl, Thomas E.
AU - Kurniawan, Fredy
AU - Orellana, Kayo
AU - Zhang, Wei
AU - Grandgenett, Duane P.
AU - Harris, Reuben S.
AU - Sundborger-Lunna, Anna C.
AU - Aihara, Hideki
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-020-16963-6
DO - 10.1038/s41467-020-16963-6
M3 - Article
C2 - 32561747
AN - SCOPUS:85086734970
SN - 2041-1723
VL - 11
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 3121
ER -
