rapid accumulation of virulent rift valley fever virus in mice from an attenuated virus carrying a single nucleotide substitution in the m rna快速积累毒性裂谷热从一个减毒病毒携带病毒在小鼠单核苷酸替换的m rna.pdfVIP

Rapid Accumulation of Virulent Rift Valley Fever Virus in Mice from an Attenuated Virus Carrying a Single Nucleotide Substitution in the M RNA 1 1,2 1¤a 1 John C. Morrill , Tetsuro Ikegami , Naoko Yoshikawa-Iwata , Nandadeva Lokugamage , Sungyong 1¤b 1 1¤a 1,2 1 Won , Kaori Terasaki , Aya Zamoto-Niikura , C. J. Peters *, Shinji Makino * 1 Department of Microbiology and Immunology, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States of America, 2 Department of Pathology, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States of America Abstract Background: Rift Valley fever virus (RVFV), a member of the genus Phlebovirus within the family Bunyaviridae, is a negative- stranded RNA virus with a tripartite genome. RVFV is transmitted by mosquitoes and causes fever and severe hemorrhagic illness among humans, while in livestock it causes fever and high abortion rates. Methodology/Principal Findings: Sequence analysis showed that a wild-type RVFV ZH501 preparation consisted of two major viral subpopulations, with a single nucleotide heterogeneity at nucleotide 847 of M segment (M847); one had a G residue at M847 encoding glycine in a major viral envelope Gn protein, while the other carried A residue encoding glutamic acid at the corresponding site. Two ZH501-derived viruses, rZH501-M847-G and rZH501-M847-A, carried identical genomic sequences, except that the former and the latter had G and A, respectively, at M847 were recovered by using a reverse genetics system. Intraperitoneal inoculation of rZ