title: Increased blood-brain barrier permeability is not a primary determinant for lethality of West Nile virus infection in rodents.
abstract: Blood-brain barrier (BBB) permeability was evaluated in mice and hamsters infected with West Nile virus (WNV, flavivirus) as compared to those infected with Semliki Forest (alphavirus) and Banzi (flavivirus) viruses. BBB permeability was determined by measurement of fluorescence in brain homogenates or cerebrospinal fluid (CSF) after intraperitoneal (i.p.) injection of sodium fluorescein, by macroscopic examination of brains after i.p. injection of Evans blue, or by measurement of total protein in CSF compared to serum. Lethal infection of BALB/c mice with Semliki Forest virus and Banzi virus caused the brain : serum fluorescence ratios to increase from a baseline of 2-4% to as high as 11 and 15%, respectively. Lethal infection of BALB/c mice with WNV did not increase BBB permeability. When C57BL/6 mice were used, BBB permeability was increased in some, but not all, of the WNV-infected animals. A procedure was developed to measure BBB permeability in live WNV-infected hamsters by comparing the fluorescence in the CSF, aspirated from the cisterna magnum, with the fluorescence in the serum. Despite a time-dependent tendency towards increased BBB permeability in some WNV-infected hamsters, the highest BBB permeability values did not correlate with mortality. These data indicated that a measurable increase in BBB permeability was not a primary determinant for lethality of WNV infection in rodents. The lack of a consistent increase in BBB permeability in WNV-infected rodents has implications for the understanding of viral entry, viral pathogenesis and accessibility of the CNS of rodents to drugs or effector molecules.
authors.affiliation: Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT 84322-4700, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Morrey
authors.affiliation: Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT 84322-4700, USA.
authors.forename: Aaron L
authors.initials: AL
authors.lastname: Olsen
authors.affiliation: Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT 84322-4700, USA.
authors.forename: Venkatraman
authors.initials: V
authors.lastname: Siddharthan
authors.affiliation: Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT 84322-4700, USA.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Motter
authors.affiliation: Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT 84322-4700, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT 84322-4700, USA.
authors.forename: Brandon S
authors.initials: BS
authors.lastname: Taro
authors.affiliation: Center for Integrated Biosystems, Utah State University, Logan, UT 84322-4700, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.affiliation: Center for Integrated Biosystems, Utah State University, Logan, UT 84322-4700, USA.
authors.forename: Duane
authors.initials: D
authors.lastname: Ruffner
authors.affiliation: Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT 84322-4700, USA.
authors.forename: Jeffery O
authors.initials: JO
authors.lastname: Hall
mesh_terms: D018354:Alphavirus Infections / Q000097:blood / Q000134:cerebrospinal fluid / Q000503:physiopathology; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D002199:Capillary Permeability; D006224:Cricetinae; D004195:Disease Models, Animal; D018177:Flavivirus Infections / Q000097:blood / Q000134:cerebrospinal fluid / Q000401:mortality / Q000503:physiopathology*; D005453:Fluorescence; D051379:Mice; D008807:Mice, Inbred BALB C; D012672:Semliki forest virus / Q000276:immunology / Q000472:pathogenicity; D013194:Staining and Labeling; D014901:West Nile Fever / Q000097:blood / Q000134:cerebrospinal fluid / Q000401:mortality / Q000503:physiopathology*; D014902:West Nile virus / Q000276:immunology / Q000472:pathogenicity*