Persistent West Nile virus associated with a neurological sequela in hamsters identified by motor unit number estimation.

Abstract:

:To investigate the hypothesis that neurological sequelae are associated with persistent West Nile virus (WNV) and neuropathology, we developed an electrophysiological motor unit number estimation (MUNE) assay to measure the health of motor neurons temporally in hamsters. The MUNE assay was successful in identifying chronic neuropathology in the spinal cords of infected hamsters. MUNE was suppressed at days 9 to 92 in hamsters injected subcutaneously with WNV, thereby establishing that a long-term neurological sequela does occur in the hamster model. MUNE suppression at day 10 correlated with the loss of neuronal function as indicated by reduced choline acetyltransferase staining (R(2) = 0.91). Between days 10 and 26, some alpha-motor neurons had died, but further neuronal death was not detected beyond day 26. MUNE correlated with disease phenotype, because the lowest MUNE values were detected in paralyzed limbs. Persistent WNV RNA and foci of WNV envelope-positive cells were identified in the central nervous systems of all hamsters tested from 28 to 86 days. WNV-positive staining colocalized with the neuropathology, which suggested that persistent WNV or its products contributed to neuropathogenesis. These results established that persistent WNV product or its proteins cause dysfunction, that WNV is associated with chronic neuropathological lesions, and that this neurological sequela is effectively detected by MUNE. Inasmuch as WNV-infected humans can also experience a poliomyelitis-like disease where motor neurons are damaged, MUNE may also be a sensitive clinical or therapeutic marker for those patients.

journal_name

J Virol

journal_title

Journal of virology

authors

Siddharthan V,Wang H,Motter NE,Hall JO,Skinner RD,Skirpstunas RT,Morrey JD

doi

10.1128/JVI.00017-09

subject

Has Abstract

pub_date

2009-05-01 00:00:00

pages

4251-61

issue

9

eissn

0022-538X

issn

1098-5514

pii

JVI.00017-09

journal_volume

83

pub_type

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