Persistent infection and associated nucleotide changes of West Nile virus serially passaged in hamsters

Wu, Xiaoyan; Lü, Liang; Guzmán, Hilda; Tesh, Robert B.; Xiao, Shu Yuan

doi:10.1099/vir.0.2008/003210-0

Cited by 19 publications

(18 citation statements)

References 32 publications

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“…More recently, WNV was also isolated predominantly from the urine and kidneys but not the brains of hamsters inoculated intraperitoneally with WNV (42,43). The persistent viruses isolated from the urine of these hamsters were determined to have lost neurovirulence with concomitant genotypic changes in the coding regions (45). As with the primate studies, the viruses isolated from the hamsters were genotypically and phenotypically altered (9).…”

mentioning

confidence: 79%

Persistent West Nile Virus Associated with a Neurological Sequela in Hamsters Identified by Motor Unit Number Estimation

Siddharthan

Wang

Motter

et al. 2009

J Virol

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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 ␣-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.

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mentioning

confidence: 79%

Persistent West Nile Virus Associated with a Neurological Sequela in Hamsters Identified by Motor Unit Number Estimation

Siddharthan

Wang

Motter

et al. 2009

J Virol

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“…Replication in epithelial cells, therefore, is likely to be important for virus dissemination throughout the organism. Recent observations have demonstrated that WNV can be shed in the urine of infected mammals (44,(51)(52)(53)60). Replication of the virus in the kidney and the perturbation of barrier function may contribute to this phenomenon, suggesting a potential mechanism for viral persistence and spread.…”

Section: Discussionmentioning

confidence: 99%

West Nile Virus Capsid Degradation of Claudin Proteins Disrupts Epithelial Barrier Function

Medigeshi

Hirsch

Brien

et al. 2009

J Virol

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During acute infection, West Nile virus (WNV) has been reported to infect a variety of cell types in various tissues of both experimentally and naturally infected hosts. Virus infects epithelial cells in the skin, kidney, intestine, and testes, although the importance of these findings is unclear. In the current study, we have observed that WNV infection of kidney tubules in mice coincides with the loss of expression of several members of the claudin family. Proteins of this family are often involved in epithelial barrier formation and function. WNV infection of epithelial cells in culture resulted in a decrease in the transepithelial electrical resistance, an increase in the efflux of mannitol across the monolayer, and a loss of intracellular levels of claudin-1 to -4. WNV capsid alone was sufficient for the degradation event, which was mediated through lysosomal proteases. Since epithelial cells are frequent sites of WNV infection, these observations imply a potential mechanism for virus dissemination and extraneural pathogenesis.

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“…However, the risk to the recipient would appear to be low. In the case of WN, virus associated with chronic infection in hamsters and monkeys have multiple mutations, reduced virulence and altered biological functions [106]. In a single report, bone marrow from a donor twin vaccinated 1 month earlier with 17D was transplanted to an identical twin [107].…”

Section: Virus Shedding Persistent Infection Transfusion Contact Smentioning

confidence: 99%

Review of the risks and benefits of yellow fever vaccination including some new analyses

Monath

2012

Expert Review of Vaccines

126

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The live, attenuated yellow fever (YF) 17D vaccine provides highly effective and durable immunity and is widely used for travelers to and residents of endemic areas of South America and Africa. Neurotropic and viscerotropic serious adverse events associated with these vaccines occur rarely, but YF 17D vaccine-associated viscerotropic disease (YEL-AVD) is notable for its lethality. There appear to be two distinct patterns of risk for YEL-AVD: the first in younger persons, particularly women, with defects in innate immunity, in whom the case-fatality rate is higher; and the second in elderly persons, particularly men with age-related immune senescence and a lower case-fatality rate. From 1990 to the present, the number of cases (n = 31) and deaths (n = 12) from YEL-AVD in travelers has exceeded the reports of YF (n = 6) acquired by natural infection, raising the question whether the risk of vaccination exceeds the benefit in travelers. To provide some guidance on this point, the rate of vaccine-related injury is compared with the rate of naturally acquired disease in a new analysis that estimates the immunologically susceptible denominator population in YF endemic and epidemic areas. For many years, the risk of vaccine-related illness and death was similar to the risk of illness and death from natural infection with YF in South America. Africa posed a substantially higher estimated risk of wild-type YF than vaccine-related injury. Multiple factors should be considered in making decisions about YF vaccination, including specific destination, season of the year, local evidence for YF transmission, likelihood of exposure to vector mosquitoes and individual risk factors for YEL-AVD, with the goal of increasing vaccine coverage for travel to high-risk areas and reducing unnecessary vaccination. Prospects for future, safer vaccines are also described.

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Persistent infection and associated nucleotide changes of West Nile virus serially passaged in hamsters

Cited by 19 publications

References 32 publications

Persistent West Nile Virus Associated with a Neurological Sequela in Hamsters Identified by Motor Unit Number Estimation

Persistent West Nile Virus Associated with a Neurological Sequela in Hamsters Identified by Motor Unit Number Estimation

West Nile Virus Capsid Degradation of Claudin Proteins Disrupts Epithelial Barrier Function

Review of the risks and benefits of yellow fever vaccination including some new analyses

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