Visualizing a viral infection as it happens

2012

Challenge

Retroviruses, such as the human immunodeficiency virus (HIV), initiate infection when the viral membrane fuses with host cells, a process mediated by viral proteins and cellular receptors. But scientists need a more detailed understanding of the mechanism in order to develop drugs that can impede the fusion.

Advance

IRP researchers led by Alasdair Steven, Ph.D., used cryo-electron tomography (cryo-ET), a technique that allows three-dimensional imaging of individual virus particles at molecular resolution, to visualize successive stages of virus-host cell fusion in a bird retrovirus model. They succeeded in viewing a specific “pre-hairpin” conformation of the interaction, a long hypothesized key intermediate of fusion that had never been directly visualized.

Impact

This discovery has informed many advanced investigations of fusion dynamics, including those of other retroviruses, such as HIV and the influenza virus, which infect by a similar mechanism.

Publications

Cardone G, Brecher M, Fontana J, Winkler DC, Butan C, White JM, Steven AC. (2012). Visualization of the two-step fusion process of the retrovirus avian sarcoma/leukosis virus by cryo-electron tomography. J Virol. 86(22), 12129-37.