Nature 383, 350 - 354 (26 September 1996); doi:10.1038/383350a0

Neutralizing antibody to human rhinovirus 14 penetrates the receptor-binding canyon

Thomas J. Smith, Elaine S. Chase, Timothy J. Schmidt, Norman H. Olson & Timothy S. Baker

Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907-1392, USA

THE three-dimensional structure of intact human rhinovirus 14 (HRV-14) complexed with Fab fragments (Fabl7-IA) from a strongly neutralizing antibody that binds bivalently to the virion^1,2 has been determined to 4.0 Å resolution by a combination of X-ray crystallography and cryo-electron microscopy. In contradiction to the most commonly held model of antibody-mediated neutralization, Fab17-IA does not induce a conformational change in the HRV-14 capsid. Instead, the paratope of the antibody undergoes a large conformational change to accommodate the epitope. Unlike any previously described antibody–antigen structure, the conserved framework region of the antibody makes extensive contact with the viral surface. Fabl7-IA penetrates deep within the canyon in which the cellular receptor for HRV-14 binds^3,4. Hence, it is unlikely that viral quaternary structure evolves merely to evade immune recognition. Instead, the shape and position of the receptor-binding region on a virus probably dictates receptor binding and subsequent uncoating events and has little or no influence on concealing the virus from the immune system.

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