Localization of a Region in the Fusion Protein of Avian Metapneumovirus That Modulates Cell-Cell Fusion |
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| Authors: | Yongwei Wei Kurtis Feng Xiangjie Yao Hui Cai Junan Li Anne M Mirza Ronald M Iorio Jianrong Li |
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| Institution: | aDepartment of Food Science and Technology, College of Food, Agricultural and Environmental Sciences;bDivision of Environmental Health Sciences, College of Public Health;cCenter for RNA Biology, The Ohio State University, Columbus, Ohio, USA;dDepartment of Microbiology and Physiological Systems;eProgram in Immunology and Virology, University of Massachusetts Medical School, Worcester, Massachusetts, USA |
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| Abstract: | The genus Metapneumovirus within the subfamily Pneumovirinae of the family Paramyxoviridae includes two members, human metapneumovirus (hMPV) and avian metapneumovirus (aMPV), causing respiratory tract infections in humans and birds, respectively. Paramyxoviruses enter host cells by fusing the viral envelope with a host cell membrane. Membrane fusion of hMPV appears to be unique, in that fusion of some hMPV strains requires low pH. Here, we show that the fusion (F) proteins of aMPV promote fusion in the absence of the attachment protein and low pH is not required. Furthermore, there are notable differences in cell-cell fusion among aMPV subtypes. Trypsin was required for cell-cell fusion induced by subtype B but not subtypes A and C. The F protein of aMPV subtype A was highly fusogenic, whereas those from subtypes B and C were not. By construction and evaluation of chimeric F proteins composed of domains from the F proteins of subtypes A and B, we localized a region composed of amino acid residues 170 to 338 in the F protein that is responsible for the hyperfusogenic phenotype of the F from subtype A. Further mutagenesis analysis revealed that residues R295, G297, and K323 in this region collectively contributed to the hyperfusogenicity. Taken together, we have identified a region in the aMPV F protein that modulates the extent of membrane fusion. A model for fusion consistent with these data is presented. |
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