the curious case of arenavirus entry, and its inhibition好奇的沙粒病毒条目,及其抑制.pdfVIP

Viruses 2012, 4, 83-101; doi:10.3390/v4010083 OPEN ACCESS viruses ISSN 1999-4915 /journal/viruses Review The Curious Case of Arenavirus Entry, and Its Inhibition Jack H. Nunberg * and Joanne York Montana Biotechnology Center, The University of Montana, Missoula, MT 59812, USA; E-Mail: joanne.york@ * Author to whom correspondence should be addressed; E-Mail: jack.nunberg@; Tel.: +1-406-243-6421. Received: 28 October 2011; in revised form: 7 December 2011 / Accepted: 5 January 2012 / Published: 13 January 2012 Abstract: Arenaviruses comprise a diverse family of enveloped negative-strand RNA viruses that are endemic to specific rodent hosts worldwide. Several arenaviruses cause severe hemorrhagic fevers in humans, including Junín and Machupo viruses in South America and Lassa fever virus in western Africa. Arenavirus entry into the host cell is mediated by the envelope glycoprotein complex, GPC. The virion is endocytosed on binding to a cell-surface receptor, and membrane fusion is initiated in response to physiological acidification of the endosome. As with other class I virus fusion proteins, GPC-mediated membrane fusion is promoted through a regulated sequence of conformational changes leading to formation of the classical postfusion trimer-of-hairpins structure. GPC is, however, unique among the c