Abstract
Prior findings led us to hypothesize that West Nile virus (WNV) preferentially transports along motor axons instead of sensory axons. WNV is known to undergo axonal transport in cell culture and in infected hamsters to infect motor neurons in the spinal cord. To investigate this hypothesis, WNV was injected directly into the left sciatic nerve of hamsters. WNV envelope-staining in these hamsters was only observed in motor neurons of the ipsilateral ventral horn of the spinal cord, but not in the dorsal root ganglion (DRG). To evaluate the consequence of motor neuron infection by WNV, the authors inoculated wheat germ agglutinin—horseradish peroxidase (WGA-HRP) 9 days after WNV sciatic nerve injection, and stained the spinal cord and the DRG for HRP activity 3 days later. The degree of HRP-staining in DRG was the same in WNV- and sham-infected animals, but the HRP-staining in the motor neuron in the ventral horn was considerably less for WNV-infected hamsters. To investigate the mechanism of WNV transport, hamsters were treated with colchicine, an inhibitor of membranous microtubule-mediated transport. The intensity of the WNV-stained area in the spinal cord of colchicine-treated hamsters at 6 days after WNV infection were significantly reduced (P≤.05) compared to the placebo-treated hamsters. These data suggest that WNV is preferentially transported through the motor axons, but not the sensory axons, to subsequently infect motor neurons and cause motor weakness and paralysis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Chen CS, Yao YC, Lin SC, Lee YP, Wang YF, Wang JR, Liu CC, Lei HY, Yu CK (2007). Retrograde axonal transport: a major transmission route of enterovirus 71 in mice. J Virol 81: 8996–9003.
Darman J, Backovic S, Dike S, Maragakis NJ, Krishnan C, Rothstein JD, Irani DN, Kerr DA (2004). Viral-induced spinal motor neuron death is non-cell-autonomous and involves glutamate excitotoxicity. J Neurosci 24: 7566–7575.
Davis CT, Beasley DW, Guzman H, Siirin M, Parsons RE, Tesh RB, Barrett AD (2004). Emergence of attenuated West Nile virus variants in Texas, 2003. Virology 330: 342–350.
Griffin JW, Hoffman PN, Clark AW, Carroll PT, Price DL (1978). Slow axonal transport of neurofilament proteins: impairment of beta,beta′-iminodipropionitrile administration. Science 202: 633–635.
Hippenmeyer S, Vrieseling E, Sigrist M, Portmann T, Laengle C, Ladle DR, Arber S (2005). A developmental switch in the response of DRG neurons to ETS transcription factor signaling. PLoS Biol 3: e159.
Hunsperger E, Roehrig JT (2005). Characterization of West Nile viral replication and maturation in peripheral neurons in culture. J NeuroVirol 11: 11–22.
Hunsperger EA, Roehrig JT (2006). Temporal analyses of the neuropathogenesis of a West Nile virus infection in mice. J NeuroVirol 12: 129–139.
Karlsson JO, Hansson HA, Sjostrand. J (1971). Effect of colchicine on axonal transport and morphology of retinal ganglion cells. Z Zellforsch Mikrosk Anat 115: 265–283.
Lanciotti RS, Kerst AJ (2001). Nucleic acid sequence-based amplification assays for rapid detection of West Nile and St. Louis encephalitis viruses. J Clin Microbiol 39: 4506–4513.
Lanciotti RS, Ebel GD, Deubel V, Kerst AJ, Murri S, Meyer R, Bowen M, McKinney N, Morrill WE, Crabtree MB, Kramer LD, Roehrig JT (2002). Complete genome sequences and phylogenetic analysis of West Nile virus strains isolated from the United States, Europe, and the Middle East. Virology 298: 96–105.
Liu H, Llewellyn-Smith IJ, Basbaum AI (1995). Co-injection of wheat germ agglutinin-HRP and choleragenoid-HRP into the sciatic nerve of the rat blocks transganglionic transport. J Histochem Cytochem 43: 489–495.
Llorens J, Crofton KM, O’Callaghan JP (1993). Administration of 3,3′-iminodipropionitrile to the rat results in region-dependent damage to the central nervous system at levels above the brain stem. J Pharmacol Exp Therapeut 265: 1492–1498.
Morrell JI, Greenberger LM, Pfaff DW (1981). Comparison of horseradish peroxidase visualization methods: quantitative results and further technical specifics. J Histochem Cytochem 29: 903–916.
Morrey JD, Siddharthan V, Olsen AL, Wang H, Julander JG, Hall JO, Li H, Nordstrom JL, Koenig S, Johnson S, Diamond MS (2007). Defining the limit of effective treatment for West Nile virus neurological infection with a humanized neutralizing monoclonal antibody. Antimicrob Agents Chemother 51: 2396–2402.
Morrey JD, Siddharthan V, Wang H, Hall JO, Skirpstunas RT, Nordstrom JL, Koenig S, Johnson S, Diamond MS (2008). West Nile virus—induced acute flaccid paralysis is prevented by monoclonal antibody treatment even after infection of spinal cord neurons. J NeuroVirol 14: 152–163.
Noguchi M, Kikuchi H, Ishibashi M, Noda S (2003). Percentage of the positive area of bone metastasis is an independent predictor of disease death in advanced prostate cancer. Br J Cancer 88: 195–201.
Ohka S, Matsuda N, Tohyama K, Oda T, Morikawa M, Kuge S, Nomoto A (2004). Receptor (CD155)-dependent endocytosis of poliovirus and retrograde axonal transport of the endosome. J Virol 78: 7186–7198.
Ohka S, Yang WX, Terada E, Iwasaki K, Nomoto. A (1998). Retrograde transport of intact poliovirus through the axon via the fast transport system. Virology 250: 67–75.
Oztas E (2003). Neuronal tracing. Neuroanatomy 2: 2–5.
Romero MI, Romero MA, Smith GM (1999). Visualization of axonally transported horseradish peroxidase using enhanced immunocytochemical detection: a direct comparison with the tetramethylbenzidine method. J Histochem Cytochem 47: 265–272.
Samuel MA, Morrey JD, Diamond. MS (2007a). Caspase-3 dependent cell death of neurons contributes to the pathogenesis of West Nile virus encephalitis. J Virol 81: 2614–2623.
Samuel MA, Wang H, Siddharthan V, Morrey JD, Diamond MS (2007b). Axonal transport mediates West Nile virus entry into the central nervous system and induces acute flaccid paralysis. Proc Natl Acad Sci U S A 104: 17140–17145.
Tsiang H, Lycke E, Ceccaldi PE, Ermine A, Hirardot X (1989). The anterograde transport of rabies virus in rat sensory dorsal root ganglia neurons. J Gen Virol 70 Pt 8: 2075–2085.
Weiss L, Weiss J, Pobre T, Kalman A (2004). Nerve conduction studies. In: Easy EMG, Weiss L, Silver J, Weiss J (eds). London: Butterworth Heinemann. pp. 17–40.
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was funded by NIH N01-AI-15435 (J.D.M.) Virology Branch, NIAID, NIH; 1-U54 AI06357-01 Rocky Mountain Regional Centers of Excellence (J.D.M.), and Utah Agricultural Research Station no. UTA00424.
Rights and permissions
About this article
Cite this article
Wang, H., Siddharthan, V., Hall, J.O. et al. West Nile virus preferentially transports along motor neuron axons after sciatic nerve injection of hamsters. Journal of NeuroVirology 15, 293–299 (2009). https://doi.org/10.1080/13550280902973978
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1080/13550280902973978