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1、8. W. D. Lawton, M. J. Surgalla, J. Infect. Dis. 113, 39 (1963). 9. A. V. Philipovskiy et al., Infect. Immun. 73, 1532 (2005). 10. T. Kubori et al., Science 280, 602 (1998). 11. F. S. Cordes et al., J. Biol. Chem. 278, 17103 (2003). 12. E. Hoiczyk, G. Blobel, Proc. Natl. Acad. Sci. U.S.A. 98, 4669 (
2、2001). 13. L. Journet, C. Agrain, P. Broz, G. R. Cornelis, Science 302, 1757 (2003). 14. Yersinia builds injectisomes when the temperature reaches 37-C, the hosts body temperature. Yop secretion is triggered by contact with a target cell or artificially by chelation of Ca2ions (15). 15. Materials an
3、d methods are available as supporting material on Science Online. 16. Removal of lcrV leads to reduced synthesis of YopB and YopD because of a regulatory effect of LcrV on their expression. This undesired effect can be com- pensated by deleting yopQ (5). 17. C. A. Mueller et al., unpublished data. 1
4、8. W. L. Picking et al., Infect. Immun. 73, 1432 (2005). 19. S. J. Daniell et al., Cell. Microbiol. 3, 865 (2001). 20. D. Chakravortty, M. Rohde, L. Jager, J. Deiwick, M. Hensel, EMBO J. 24, 2043 (2005). 21. We thank P. Jeno for mass spectrometry analyses, M. Duerrenberger for use of the TEM facilit
5、y, and J. M. Meyer and J. Frey for supplying P. aeruginosa PAO1 and A. salmonicida JF2267. Supported by the Swiss National Science Foundation (grant nos. 32- 65393.01 to G.C. and 3100-059415 to A.E.) and by the Maurice E. Mu ller Foundation of Switzerland. Supporting Online Material www.sciencemag.o
6、rg/cgi/content/full/310/5748/674/ DC1 Materials and Methods Figs. S1 to S8 Tables S1 and S2 References and Notes 5 August 2005; accepted 4 October 2005 10.1126/science.1118476 Bats Are Natural Reservoirs of SARS-Like Coronaviruses Wendong Li,1,2Zhengli Shi,2* Meng Yu,3Wuze Ren,2Craig Smith,4 Jonatha
7、n H. Epstein,5Hanzhong Wang,2Gary Crameri,3 Zhihong Hu,2Huajun Zhang,2Jianhong Zhang,2 Jennifer McEachern,3Hume Field,4Peter Daszak,5 Bryan T. Eaton,3Shuyi Zhang,1,6* Lin-Fa Wang3* Severe acute respiratory syndrome (SARS) emerged in 2002 to 2003 in southern China. The origin of its etiological agent
8、, the SARS coronavirus (SARS-CoV), remains elusive. Here we report that species of bats are a natural host of coronaviruses closely related to those responsible for the SARS outbreak. These viruses, termed SARS-like coronaviruses (SL-CoVs), display greater genetic variation than SARS-CoV isolated fr
9、om humans or from civets. The human and civet isolates of SARS-CoV nestle phylogenetically within the spectrum of SL- CoVs, indicating that the virus responsible for the SARS outbreak was a member of this coronavirus group. Severe acute respiratory syndrome (SARS) was caused by a newly emerged coron
10、avirus, now known as SARS coronavirus (SARS-CoV) (1, 2). In spite of the early success of etio- logical studies and molecular characterization of this virus (3, 4), efforts to identify the ori- gin of SARS-CoV have been less successful. Without knowledge of the reservoir host dis- tribution and tran
11、smission routes of SARS- CoV, it will be difficult to prevent and control future outbreaks of SARS. Studies conducted previously on animals sampled from live animal markets in Guang- dong, China, indicated that masked palm civets (Paguma larvata) and two other species had been infected by SARS-CoV (
12、5). This led to a large-scale culling of civets to prevent fur- ther SARS outbreaks. However, subsequent studies have revealed no widespread infection in wild or farmed civets (6, 7). Experimental infection of civets with two different human isolates of SARS-CoV resulted in overt clin- ical symptoms
13、, rendering them unlikely to be the natural reservoir hosts (8). These data sug- gest that although P. larvata may have been the source of the human infection that pre- cipitated the SARS outbreak, infection in this and other common species in animal markets was more likely a reflection of an Bartif
14、icial market cycle in naBve species than an indi- cation of the natural reservoir of the virus. Bats are reservoir hosts of several zoonotic viruses, including the Hendra and Nipah viruses, which have recently emerged in Australia and East Asia, respectively (911). Bats may be persistently infected
15、with many viruses but rarely display clinical symptoms (12). These charac- teristics and the increasing presence of bats and bat products in food and traditional medicine markets in southern China and elsewhere in Asia (13) led us to survey bats in the search for the natural reservoir of SARS-CoV. I
16、n this study, conducted from March to December of 2004, we sampled 408 bats representing nine species, six genera, and three families from four locations in China (Guangdong, Guangxi, Hubei, and Tianjin) af- ter trapping them in their native habitat (Table 1). Blood, fecal, and throat swabs were col- lected; serum samples and cDNA from fecal or throat samples were independently analyzed, double-blind, with different methods in our laboratories in Wuhan and Geelong (14). Among six genera of bat
