9ZY0

Cryo-EM structure of the monomeric HIV-2 Vif-human APOBEC3H-CBFbeta complex

Summary for 9ZY0

• Entry DOI: 10.2210/pdb9zy0/pdb
• EMDB information: 74939
• Descriptor: Virion infectivity factor, Core-binding factor subunit beta, Single-stranded DNA cytosine deaminase, ... (6 entities in total)
• Functional Keywords: hiv-2, vif, apobec3h, antagonism, ubiquitination, antiviral protein, antiviral protein-rna complex, antiviral protein/rna
• Biological source: Human immunodeficiency virus 2; More
• Total number of polymer chains: 5
• Total formula weight: 73474.07

Authors

Niu, Y.,Lilly, M.,Ronayne, E.K.,Emerman, M.,Chesarino, N.M.,Gross, J.D. (deposition date: 2026-01-05, release date: 2026-07-15)

Primary citation

Niu, Y.,Lilly, M.,Ronayne, E.K.,Emerman, M.,Chesarino, N.M.,Gross, J.D.
The structural mechanism of HIV-2 Vif antagonism of human APOBEC3H.
Nat Commun, 2026

PubMed Abstract: Human APOBEC3 (A3) proteins restrict retrovirus infection by inducing hypermutations in viral cDNA. To counteract this restriction, lentiviruses, such as HIV-1 and HIV-2 encode the viral infectivity factor (Vif), which hijacks a host Cullin-RING E3 ubiquitin ligase complex to target A3 proteins for proteasomal degradation. Here, we present the cryo-EM structure of HIV-2 Vif in complex with human A3H and CBFβ. The structure reveals that A3H forms a dimer mediated by dsRNA where each A3H monomer directly interacts with an HIV-2 Vif and the host protein CBFβ. Both HIV-2 Vif-A3H and CBFβ-A3H interfaces are critical for A3H degradation. Notably, however, the HIV-2 Vif-A3H interface is entirely distinct from the previously determined cryo-EM structure of the HIV-1 Vif and A3H complex. These findings suggest that HIV-1 and HIV-2 Vif, which are the result of distinct cross-species transmissions from species with different A3H characteristics, have followed separate evolutionary trajectories to counteract human A3H.

PubMed: 42373647
DOI: 10.1038/s41467-026-75045-1

Experimental method

ELECTRON MICROSCOPY (3.2 Å)