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Breaking In: Human Metapneumovirus Fusion and Entry
Vanderbilt University School of Medicine, Department of Pathology, Microbiology and Immunology, 1161 21st Ave. S., Nashville, TN 37232, USA
Vanderbilt University School of Medicine, Departments of Pediatrics and Pathology, Microbiology, and Immunology, 1161 21st Ave. S., Nashville, TN 37232, USA
* Author to whom correspondence should be addressed.
Received: 14 December 2012; in revised form: 9 January 2013 / Accepted: 10 January 2013 / Published: 16 January 2013
Abstract: Human metapneumovirus (HMPV) is a leading cause of respiratory infection that causes upper airway and severe lower respiratory tract infections. HMPV infection is initiated by viral surface glycoproteins that attach to cellular receptors and mediate virus membrane fusion with cellular membranes. Most paramyxoviruses use two viral glycoproteins to facilitate virus entry—an attachment protein and a fusion (F) protein. However, membrane fusion for the human paramyxoviruses in the Pneumovirus subfamily, HMPV and respiratory syncytial virus (hRSV), is unique in that the F protein drives fusion in the absence of a separate viral attachment protein. Thus, pneumovirus F proteins can perform the necessary functions for virus entry, i.e., attachment and fusion. In this review, we discuss recent advances in the understanding of how HMPV F mediates both attachment and fusion. We review the requirements for HMPV viral surface glycoproteins during entry and infection, and review the identification of cellular receptors for HMPV F. We also review our current understanding of how HMPV F mediates fusion, concentrating on structural regions of the protein that appear to be critical for membrane fusion activity. Finally, we illuminate key unanswered questions and suggest how further studies can elucidate how this clinically important paramyxovirus fusion protein may have evolved to initiate infection by a unique mechanism.
Keywords: metapneumovirus; fusion protein; paramyxovirus; integrin
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MDPI and ACS Style
Cox, R.G.; Williams, J.V. Breaking In: Human Metapneumovirus Fusion and Entry. Viruses 2013, 5, 192-210.
Cox RG, Williams JV. Breaking In: Human Metapneumovirus Fusion and Entry. Viruses. 2013; 5(1):192-210.
Cox, Reagan G.; Williams, John V. 2013. "Breaking In: Human Metapneumovirus Fusion and Entry." Viruses 5, no. 1: 192-210.