Identification of antibody neutralization epitopes on the fusion protein of human metapneumovirus

Abstract

Human metapneumovirus (hMPV) is genetically related to respiratory syncytial virus (RSV); both cause respiratory tract illnesses ranging from a mild cough to bronchiolitis and pneumonia. The F protein-directed monoclonal antibody (mAb) palivizumab has been shown to prevent severe lower respiratory tract RSV infection in animals and humans. We have previously reported on a panel of mAbs against the hMPV F protein that neutralize hMPV in vitro and, in two cases, in vivo. Here we describe the generation of hMPV mAb-resistant mutants (MARMs) to these neutralizing antibodies. Sequencing the F proteins of the hMPV MARMs identified several neutralizing epitopes. Interestingly, some of the epitopes mapped on the hMPV F protein coincide with homologous regions mapped previously on the RSV F protein, including the site against which the broadly protective mAb palivizumab is directed. This suggests that these homologous regions play important, conserved functions in both viruses.

Fig. 1.

Schematic depiction of hMPV and RSV F protein domain structures and relative location of MARM mutation sites. Indicated are the N terminus (N), signal peptide (SP), fusion peptide (FP), heptad repeat 1 (HR1), heptad repeat 2 (HR2), transmembrane domain (TM) and C terminus (C), as well as the F1 and F2 segments of the F protein. The amino acid positions that border domains (predicted) or cleavage sites and C termini (known) are indicated. Also depicted are the relative positions of the hMPV epitope group MARM mutations and corresponding MARM mutation sites on the RSV F protein (see text for details).