Ulbrandt Nancy D, Ji Hong, Patel Nita K, Barnes Arnita S, Wilson Susan, Kiener Peter A, Suzich JoAnn, McCarthy Michael P
MedImmune, Inc. 1 MedImmune Way, Gaithersburg, MD 20878, USA.
J Gen Virol. 2008 Dec;89(Pt 12):3113-3118. doi: 10.1099/vir.0.2008/005199-0.
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.
人偏肺病毒（hMPV）在基因上与呼吸道合胞病毒（RSV）相关；两者都会引发从轻度咳嗽到细支气管炎和肺炎等呼吸道疾病。F蛋白导向的单克隆抗体（mAb）帕利珠单抗已被证明可预防动物和人类严重的下呼吸道RSV感染。我们之前报道过一组针对hMPV F蛋白的单克隆抗体，它们在体外以及在两例体内实验中可中和hMPV。在此我们描述了针对这些中和抗体产生的hMPV单克隆抗体抗性突变体（MARM）。对hMPV MARM的F蛋白进行测序确定了几个中和表位。有趣的是，一些定位在hMPV F蛋白上的表位与先前定位在RSV F蛋白上的同源区域重合，包括广泛保护性单克隆抗体帕利珠单抗所针对的位点。这表明这些同源区域在两种病毒中都发挥着重要的保守功能。
