Research Highlights

Structural biology: Deadly deception

Subject Categories: Cell & molecular biology

Published online 12 February 2014


The human immunodeficiency virus uses molecular mimicry to hijack cellular proteasomal degradation pathways and evade host restriction factors

Felix Cheung

© (2014) Nature

The viral infectivity factor (Vif) is a protein found in HIV and other retroviruses. It sabotages the host immune system by subverting the activity of restriction factors, but the molecular mechanisms underlying this process are unclear.

Zhiwei Huang at the Harbin Institute of Technology and co-workers have now obtained the crystal structure of a pentameric complex comprising Vif and four host proteins: the core-binding factor beta subunit CBF-β, the scaffold protein CUL5, and substrate adaptors ELOB and ELOC. They showed that Vif promotes the degradation of restriction factors by mimicking the structure and function of suppressor of cytokine signalling 2 (SOCS2) — a key regulator of cellular proteasomal degradation pathways.

Specifically, the U-shaped pentameric complex (see image) has Vif and CBF-β on one end and CUL5 on the other. The binding of Vif to CBF-β prevents CBF-β from binding transcription factors and promoting T cell development. In addition, Vif interacts with CUL5 to promote the degradation of restriction factors, just as SOCS2 would.

The findings provide valuable insights into the structural basis for hijacking cellular proteasomal degradation pathways and lay the foundation for rational design of novel antiretroviral drugs, especially those for targeting HIV.


  1. Guo, Y. et al. Structural basis for hijacking CBF-β and CUL5 E3 ligase complex by HIV-1 Vif. Nature 505, 229–233 10.1038/nature12884 (2014).