Structural basis of host protein hijacking in human T-cell leukemia virus integration.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32561747.
- Also identified by DOI 10.1038/s41467-020-16963-6 and PMC identifier 7305164.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Host-Pathogen Interactions
- Human T-lymphotropic virus 1
- Integrases
- Protein Phosphatase 2
- Viral Proteins
- Virus Integration