title: Rift Valley fever virus lacking NSm proteins retains high virulence in vivo and may provide a model of human delayed onset neurologic disease.
abstract: Rift Valley fever virus is a significant human and veterinary pathogen responsible for explosive outbreaks throughout Africa and the Arabian Peninsula. Severe acute disease in humans includes rapid onset hepatic disease and hemorrhagic fever or delayed onset encephalitis. A highly efficient reverse genetics system was developed which allowed generation of recombinant RVF viruses to assess the role of NSm protein in virulence in a rat model in which wild-type RVF virus strain ZH501 (wt-ZH501) results in 100% lethal hepatic disease 2-3 days post infection. While extensive genomic analysis indicates conservation of the NSm coding capability of diverse RVF viruses, and viruses deficient in NSs proteins are completely attenuated in vivo, comparison of wt-ZH501, a reverse genetics generated wt-ZH501 virus (R-ZH501), and R-ZH501 virus lacking the NSm proteins (R-DeltaNSm-ZH501) demonstrated that the NSm proteins were nonessential for in vivo virulence and lethality. Surprisingly, while 44% of R-DeltaNSm-ZH501 infected animals quickly developed lethal hepatic disease similar to wt- and R-ZH501, 17% developed delayed onset neurologic disease (lethargy, head tremors, and ataxia) at 13 days post infection. Such infections may provide the basis for study of both RVF acute hepatic disease and delayed onset encephalitic disease in humans.
authors.affiliation: Special Pathogens Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road MS G-14, Atlanta, GA 30329, USA.
authors.forename: Brian H
authors.initials: BH
authors.lastname: Bird
authors.forename: César G
authors.initials: CG
authors.lastname: Albariño
authors.forename: Stuart T
authors.initials: ST
authors.lastname: Nichol
mesh_terms: D000818:Animals; D001259:Ataxia; D004195:Disease Models, Animal; D018792:Encephalitis, Viral / Q000503:physiopathology / Q000821:virology*; D005260:Female; D017353:Gene Deletion; D006524:Hepatitis, Viral, Animal / Q000503:physiopathology / Q000821:virology; D053609:Lethargy; D051381:Rats; D011920:Rats, Inbred WF; D012295:Rift Valley Fever / Q000503:physiopathology / Q000821:virology*; D012296:Rift Valley fever virus / Q000235:genetics / Q000472:pathogenicity*; D016019:Survival Analysis; D014202:Tremor; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000502:physiology; D014774:Virulence / Q000235:genetics
chemical_list: D017361:Viral Nonstructural Proteins