Vanderbilt University School of Medicine, Department of Pathology, Microbiology and Immunology, Nashville, TN 37232, USA.
Viruses. 2013 Jan 16;5(1):192-210. doi: 10.3390/v5010192.
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.
人偏肺病毒（HMPV）是一种主要的呼吸道感染病原体，可引起上呼吸道和严重的下呼吸道感染。HMPV 感染是由病毒表面糖蛋白引发的，这些糖蛋白与细胞受体结合，并介导病毒膜与细胞膜融合。大多数副粘病毒使用两种病毒糖蛋白来促进病毒进入——一种附着蛋白和一种融合（F）蛋白。然而，对于肺炎病毒亚科中的人类副粘病毒，即 HMPV 和呼吸道合胞病毒（hRSV），膜融合是独特的，因为 F 蛋白在没有单独的病毒附着蛋白的情况下驱动融合。因此，肺炎病毒 F 蛋白可以执行病毒进入所必需的功能，即附着和融合。在这篇综述中，我们讨论了对 HMPV F 介导附着和融合的机制的最新理解进展。我们回顾了 HMPV 病毒表面糖蛋白在进入和感染过程中的要求，并回顾了 HMPV F 的细胞受体的鉴定。我们还回顾了我们目前对 HMPV F 介导融合的理解，重点关注似乎对膜融合活性至关重要的蛋白质结构区域。最后，我们阐明了关键的未解决问题，并提出了进一步的研究如何阐明这种临床上重要的副粘病毒融合蛋白如何通过独特的机制引发感染。
