Nocodazole delays viral entry into the brain following footpad inoculation with West Nile virus in mice.
West Nile virus (WNV) infection in humans can cause neurological deficits, including flaccid paralysis, encephalitis, meningitis, and mental status change. To better understand the neuropathogenesis of WNV in the peripheral and the central nervous systems (PNS and CNS), we used a mouse footpad inoculation model to simulate a natural peripheral infection. Localization of WNV in the nervous system using this model has suggested two routes of viral invasion of the CNS: axonal retrograde transport (ART) from the PNS and hematogenous diffusion via a breakdown in the blood-choroid-plexus barrier. C57BL/6J mice were treated with nocodazole, a microtubule inhibitor that blocks ART, prior to infection with WNV. Nocodazole-treated WNV-infected mice developed a viremia 1.5 log(10) greater than untreated WNV-infected control mice at days 3 to 4 post infection (PI). Although viremia was greater in nocodazole-treated mice, detection of virus in brain tissue (spinal cord, cortex, brainstem, and cerebellum), as measured by real-time reverse transcriptase-polymerase chain reaction (RT-PCR), did not occur until day 7. At these later time points (7 and 9 days PI), nocodazole-treated WNV-infected animals attained viral titers in these tissues similar to titers in the untreated WNV-infected control animals. These results demonstrate that a single dose of nocodazole delays, but does not block, WNV infection of the brain.
Hunsperger
E A
EA
Centers for Disease Control and Prevention, National Center for Infectious Diseases, Division of Vector-Borne Infectious Diseases, Dengue Branch, San Juan, Puerto Rico. enh4@cdc.gov
Roehrig
J T
JT
D000818:Animals; D001921:Brain / Q000473:pathology / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015739:Nocodazole / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000235:genetics; D013997:Time Factors; D050257:Tubulin Modulators / Q000494:pharmacology*; D019562:Viral Load; D053586:Virus Internalization / Q000187:drug effects*; D014901:West Nile Fever / Q000473:pathology / Q000821:virology*; D014902:West Nile virus / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*
D012367:RNA, Viral; D050257:Tubulin Modulators; D015739:Nocodazole