Pathogenesis of Lassa Fever 英文参考文献.docVIP

Viruses 2012, 4, 2031-2048; doi:10.3390/v4102031 OPEN ACCESS viruses ISSN 1999-4915 /journal/viruses Review Pathogenesis of Lassa Fever Nadezhda E. Yun and David H. Walker* Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA; E-Mails: neyun@ (N.Y.); dwalker@ (D.W.) * Author to whom correspondence should be addressed; E-Mail: dwalker@ (D.W.); Tel.: +1-409-772-3989; Fax: +1-409-772-1850. Received: 3 September 2012; in revised form: 28 September 2012 / Accepted: 3 October 2012 / Published: 9 October 2012 Abstract: Lassa virus, an Old World arenavirus (family Arenaviridae), is the etiological agent of Lassa fever, a severe human disease that is reported in more than 100,000 patients annually in the endemic regions of West Africa with mortality rates for hospitalized patients varying between 5-10%. Currently, there are no approved vaccines against Lassa fever for use in humans. Here, we review the published literature on the life cycle of Lassa virus with the specific focus put on Lassa fever pathogenesis in humans and relevant animal models. Advancing knowledge significantly improves our understanding of Lassa virus biology, as well as of the mechanisms that allow the virus to evade the host’s immune system. However, further investigations are required in order to design improved diagnostic tools, an effective vaccine, and therapeutic agents. Keywords: arenavirus; Lassa virus; pathogenesis; cell-mediated immunity  Viruses 2012, 4 2032 1. Phylogeny and geographic distribution Lassa virus, the causative agent of Lassa fever, belongs to the family Arenaviridae. Arenaviruses are classified as segmented negative-sense RNA (nsRNA) viruses and are phylogenetically closely related to other segmented nsRNA viruses belonging to Bunyaviridae and Orthomyxoviridae. The three virus families share basic features of the intracellular replication cycle. Based on