Ljungan virus: A commentary on its association with fetal and infant morbidity and mortality in animals and humans

Krous, Henry F.; Langlois, Neil E. I.

doi:10.1002/bdra.20728

Cited by 13 publications

(9 citation statements)

References 69 publications

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“…However, in humans PUUV and TBEV infection may cause severe illness (Table 1). If LV infections cause disease in humans and/or in bank voles is controversial and remains to be clearly shown [6].…”

Section: Introductionmentioning

confidence: 99%

A Model System for In Vitro Studies of Bank Vole Borne Viruses

et al. 2011

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The bank vole (Myodes glareolus) is a common small mammal in Europe and a natural host for several important emerging zoonotic viruses, e.g. Puumala hantavirus (PUUV) that causes hemorrhagic fever with renal syndrome (HFRS). Hantaviruses are known to interfere with several signaling pathways in infected human cells, and HFRS is considered an immune-mediated disease. There is no in vitro-model available for infectious experiments in bank vole cells, nor tools for analyses of bank vole immune activation and responses. Consequently, it is not known if there are any differences in the regulation of virus induced responses in humans compared to natural hosts during infection. We here present an in vitro-model for studies of bank vole borne viruses and their interactions with natural host cell innate immune responses. Bank vole embryonic fibroblasts (VEFs) were isolated and shown to be susceptible for PUUV-infection, including a wild-type PUUV strain (only passaged in bank voles). The significance of VEFs as a model system for bank vole associated viruses was further established by infection studies showing that these cells are also susceptible to tick borne encephalitis, cowpox and Ljungan virus. The genes encoding bank vole IFN-β and Mx2 were partially sequenced and protocols for semi-quantitative RT-PCR were developed. Interestingly, PUUV did not induce an increased IFN-β or Mx2 mRNA expression. Corresponding infections with CPXV and LV induced IFN-β but not Mx2, while TBEV induced both IFN-β and Mx2.In conclusion, VEFs together with protocols developed for detection of bank vole innate immune activation provide valuable tools for future studies of how PUUV and other zoonotic viruses affect cells derived from bank voles compared to human cells. Notably, wild-type PUUV which has been difficult to cultivate in vitro readily infected VEFs, suggesting that embryonic fibroblasts from natural hosts might be valuable for isolation of wild-type hantaviruses.

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Section: Introductionmentioning

confidence: 99%

A Model System for In Vitro Studies of Bank Vole Borne Viruses

et al. 2011

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“…The pancreas from an asymptomatic bank vole, however, stained negative for LV and showed no such clusters [59]. These two studies have until now been the only to demonstrate an association between LV and diabetes in bank voles, and it has often later been stated, or taken for granted, that “LV causes diabetes in voles” [79]–[84]. However, since it is not possible to determine with accuracy whether a vole is infected with the LV, it follows that its possible role as an etiological agent responsible for diabetes in bank voles remains to be proven [60].…”

Section: Discussionmentioning

confidence: 94%

Diabetes in Danish Bank Voles (M. glareolus): Survivorship, Influence on Weight, and Evaluation of Polydipsia as a Screening Tool for Hyperglycaemia

2011

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BackgroundPrevious studies have concluded that the development of polydipsia (PD, a daily water intake ≥21 ml) among captive Danish bank voles, is associated with the development of a type 1 diabetes (T1D), based on findings of hyperglycaemia, glucosuria, ketonuria/-emia, lipemia, destroyed beta cells, and presence of autoantibodies against GAD65, IA-2, and insulin.Aim and MethodsWe retrospectively analysed data from two separate colonies of Danish bank voles in order to 1) estimate survivorship after onset of PD, 2) evaluate whether the weight of PD voles differed from non-PD voles, and, 3), evaluate a state of PD as a practical and non-invasive tool to screen for voles with a high probability of hypeglycaemia. In addition, we discuss regional differences related to the development of diabetes in Scandinavian bank voles and the relevance of the Ljungan virus as proposed etiological agent.ResultsWe found that median survival after onset of PD is at least 91 days (lower/upper quartiles = 57/134 days) with a maximum recording of at least 404 days survivorship. The development of PD did not influence the weight of Danish bank voles. The measures of accuracy when using PD as predictor of hyperglycaemia, i.e. sensitivity, specificity, positive predictive value, and negative predictive value, equalled 69%, 97%, 89%, and 89%, respectively.ConclusionThe relatively long survival of Danish PD bank voles suggests potentials for this model in future studies of the long-term complications of diabetes, of which some observations are mentioned. Data also indicates that diabetes in Danish bank is not associated with a higher body weight. Finally, the method of using measurements of daily water intake to screen for voles with a high probability of hyperglycaemia constitutes a considerable refinement when compared to the usual, invasive, methods.

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“…Taken together, these preliminary correlations imply that LV may play an important role in SIDS. However, Krous and Langlois () also reported that the evidence for LV being prominent in SIDS cases is not convincing.…”

Section: Sudden Infant Death Syndrome (Sids)mentioning

confidence: 99%

“…It has been reported that LV infection can result in type 1 diabetes mellitus, encephalitis and myocarditis (Blixt et al, ). Recently, a series of studies have found that LV is associated with severe diseases during pregnancy, such as malformation and fetal death during late pregnancy (Krous et al, ). This review focuses on stillbirth and fetal malformation.…”

Section: Ljungan Virusmentioning

confidence: 99%

Evaluation of the association of zoonotic Ljungan virus with perinatal deaths and fetal malformation

Zheng

Fang

Huang

et al. 2015

Birth Defects Research Pt C

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More and more epidemiologic and experimental data support the notion that Ljungan virus (LV), originally isolated from some rodent populations in Sweden, Denmark, and the United States, plays an important role in stillbirth and fetal malformation. Mouse dams infected with LV may result in uterine resorption and perinatal deaths that may cross generations, and their offspring may suffer high rates of malformations including cranial, brain, and limb malformations. In humans, researches founded that LV infection is related to malformation, intrauterine fetal death, and even central nervous system malformation. Although molecularly characterized, little is known about the biophysical nature of LV. Consequently, the role of LV infections in sudden infant death syndrome is still confusing, and the mechanism of how LV infections cause diseases is not clear. More research is clearly necessary to explore the mechanisms of LV infection in human and animal diseases to bring improvement to the clinical outcomes.

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Ljungan virus: A commentary on its association with fetal and infant morbidity and mortality in animals and humans

Cited by 13 publications

References 69 publications

A Model System for In Vitro Studies of Bank Vole Borne Viruses

A Model System for In Vitro Studies of Bank Vole Borne Viruses

Diabetes in Danish Bank Voles (M. glareolus): Survivorship, Influence on Weight, and Evaluation of Polydipsia as a Screening Tool for Hyperglycaemia

Evaluation of the association of zoonotic Ljungan virus with perinatal deaths and fetal malformation

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