The human metapneumovirus fusion protein mediates entry via an interaction with RGD-binding integrins.

Cox RG, Livesay SB, Johnson M, Ohi MD, Williams JV
J Virol. 2012 86 (22): 12148-60

PMID: 22933271 · PMCID: PMC3486500 · DOI:10.1128/JVI.01133-12

Paramyxoviruses use a specialized fusion protein to merge the viral envelope with cell membranes and initiate infection. Most paramyxoviruses require the interaction of two viral proteins to enter cells; an attachment protein binds cell surface receptors, leading to the activation of a fusion (F) protein that fuses the viral envelope and host cell plasma membrane. In contrast, human metapneumovirus (HMPV) expressing only the F protein is replication competent, suggesting a primary role for HMPV F in attachment and fusion. We previously identified an invariant arginine-glycine-aspartate (RGD) motif in the HMPV F protein and showed that the RGD-binding integrin αVβ1-promoted HMPV infection. Here we show that both HMPV F-mediated binding and virus entry depend upon multiple RGD-binding integrins and that HMPV F can mediate binding and fusion in the absence of the viral attachment (G) protein. The invariant F-RGD motif is critical for infection, as an F-RAE virus was profoundly impaired. Further, F-integrin binding is required for productive viral RNA transcription, indicating that RGD-binding integrins serve as receptors for the HMPV fusion protein. Thus, HMPV F is triggered to induce virus-cell fusion by interactions with cellular receptors in a manner that is independent of the viral G protein. These results suggest a stepwise mechanism of HMPV entry mediated by the F protein through its interactions with cellular receptors, including RGD-binding integrins.

MeSH Terms (15)

Amino Acid Motifs Cell Line Flow Cytometry Humans Integrins Membrane Fusion Metapneumovirus Microscopy, Electron Oligopeptides Protein Binding Receptors, Vitronectin Recombinant Proteins Viral Fusion Proteins Virion Virus Internalization

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