title: Inhibition of West Nile virus by calbindin-D28k.
abstract: Evidence indicates that West Nile virus (WNV) employs Ca(2+) influx for its replication. Moreover, calcium buffer proteins, such as calbindin D28k (CB-D28k), may play an important role mitigating cellular destruction due to disease processes, and more specifically, in some neurological diseases. We addressed the hypothesis that CB-D28k inhibits WNV replication in cell culture and infected rodents. WNV envelope immunoreactivity (ir) was not readily co-localized with CB-D28k ir in WNV-infected Vero 76 or motor neuron-like NSC34 cells that were either stably or transiently transfected with plasmids coding for CB-D28k gene. This was confirmed in cultured cells fixed on glass coverslips and by flow cytometry. Moreover, WNV infectious titers were reduced in CB-D28k-transfected cells. As in cell culture studies, WNV env ir was not co-localized with CB-D28k ir in the cortex of an infected WNV hamster, or in the hippocampus of an infected mouse. Motor neurons in the spinal cord typically do not express CB-D28k and are susceptible to WNV infection. Yet, CB-D28k was detected in the surviving motor neurons after the initial phase of WNV infection in hamsters. These data suggested that induction of CB-D28k elicit a neuroprotective response to WNV infection.
authors.affiliation: Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, Utah, United States of America.
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, Utah, United States of America.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Center for Integrated BioSystems, Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, Utah, United States of America.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Davies
authors.affiliation: Utah Veterinary Diagnostic Laboratory, Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, Utah, United States of America.
authors.forename: Jeffery O
authors.initials: JO
authors.lastname: Hall
authors.affiliation: Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, Utah, United States of America.
authors.forename: John D
authors.initials: JD
authors.lastname: Morrey
mesh_terms: D000818:Animals; D064092:Calbindin 1 / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D005260:Female; D054884:Host-Pathogen Interactions / Q000502:physiology; D008647:Mesocricetus; D051379:Mice; D008810:Mice, Inbred C57BL; D009046:Motor Neurons / Q000821:virology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000821:virology; D014709:Vero Cells; D014779:Virus Replication / Q000502:physiology; D014901:West Nile Fever / Q000503:physiopathology / Q000517:prevention & control / Q000821:virology; D014902:West Nile virus / Q000472:pathogenicity / Q000502:physiology*
chemical_list: D064092:Calbindin 1; D011994:Recombinant Proteins