5U68

Structural basis for antibody cross-neutralization of respiratory syncytial virus and human metapneumovirus

Summary for 5U68

• Entry DOI: 10.2210/pdb5u68/pdb
• Descriptor: Chimera protein of Fusion glycoprotein F0 and Envelope glycoprotein, MPE8 (2 entities in total)
• Functional Keywords: rsvf prefusion, mpe8, cross-reactive antibody neutralization, trimer, viral protein-immune system complex, viral protein/immune system
• Biological source: Human respiratory syncytial virus A (strain A2); More
• Total number of polymer chains: 6
• Total formula weight: 279411.46

Authors

Wen, X.,Jardetzky, T.S. (deposition date: 2016-12-07, release date: 2017-02-15, Last modification date: 2024-11-20)

Primary citation

Wen, X.,Mousa, J.J.,Bates, J.T.,Lamb, R.A.,Crowe, J.E.,Jardetzky, T.S.
Structural basis for antibody cross-neutralization of respiratory syncytial virus and human metapneumovirus.
Nat Microbiol, 2:16272-16272, 2017

PubMed Abstract: Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are two closely related viruses that cause bronchiolitis and pneumonia in infants and the elderly, with a significant health burden. There are no licensed vaccines or small-molecule antiviral treatments specific to these two viruses at present. A humanized murine monoclonal antibody (palivizumab) is approved to treat high-risk infants for RSV infection, but other treatments, as well as vaccines, for both viruses are still in development. Recent epidemiological modelling suggests that cross-immunity between RSV, HMPV and human parainfluenzaviruses may contribute to their periodic outbreaks, suggesting that a deeper understanding of host immunity to these viruses may lead to enhanced strategies for their control. Cross-reactive neutralizing antibodies to the RSV and HMPV fusion (F) proteins have been identified. Here, we examine the structural basis for cross-reactive antibody binding to RSV and HMPV F protein by two related, independently isolated antibodies, MPE8 and 25P13. We solved the structure of the MPE8 antibody bound to RSV F protein and identified the 25P13 antibody from an independent blood donor. Our results indicate that both antibodies use germline residues to interact with a conserved surface on F protein that could guide the emergence of cross-reactivity. The induction of similar cross-reactive neutralizing antibodies using structural vaccinology approaches could enhance intrinsic cross-immunity to these paramyxoviruses and approaches to controlling recurring outbreaks.

PubMed: 28134915
DOI: 10.1038/nmicrobiol.2016.272

Experimental method

X-RAY DIFFRACTION (3.083 Å)