Detection of JC Virus-Specific Immune Responses in a Novel Humanized Mouse Model

Tan, Chen; Broge, Thomas; Seung, Edward; Vrbanac, Vlad; Viscidi, Raphael P.; Gordon, Jennifer; Tager, Andrew M.; Koralnik, Igor J.

doi:10.1371/journal.pone.0064313

Cited by 30 publications

(34 citation statements)

References 27 publications

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“…Only recently, mice with human thymus and lymphocytes were generated to study the JCPyVspecific immune responses (13). During PyVAN and PyVHC, BKPyV replicates extensively in renal tubular epithelial cells and bladder epithelial cells, respectively (14).…”

mentioning

confidence: 99%

The Human Fetal Glial Cell Line SVG p12 Contains Infectious BK Polyomavirus

Henriksen

Tylden

Dumoulin

et al. 2014

J Virol

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The human fetal glial cell line SVG was generated in 1985 by transfecting primary fetal brain cells with a plasmid containing an origin-defective mutant of simian virus 40 (SV40). The cells, which express SV40 large T-antigen, support the replication of human JC polyomavirus (JCPyV) and have been used for JCPyV studies but also for other studies in which cells of neural origin were desirable. We intended to use the SVG p12 cells from ATCC for antiviral drug studies with JCPyV. However, during initial experiments, immunofluorescence microscopy controls unexpectedly revealed cells expressing the late viral proteins VP1, VP2/ VP3, and agno. This was confirmed by Western blotting. Since our agnoprotein antiserum is specific for BKPyV agnoprotein, infection with BKPyV was suspected. Indeed, specific BKPyV PCR of SVG p12 supernatants revealed a viral load of >1 ؋ 10

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mentioning

confidence: 99%

The Human Fetal Glial Cell Line SVG p12 Contains Infectious BK Polyomavirus

Henriksen

Tylden

Dumoulin

et al. 2014

J Virol

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“…Akute T cell leukemia (ATL) like T cell expansions [59] Dengue virus Leucocyte infection [66] Hepatitis C virus (HCV) Liver disease [69] John Cunningham (JC) virus Persistent infection [71] Influenza A virus Lung infection [72] 1 For clarity only one key reference has been listed Human fetal thymus and liver organoid…”

Section: Discussionmentioning

confidence: 99%

“…In order to understand JC virus specific immune control better, HIS mice were Christian Münz 13 intraperitoneally injected with JC virus [71]. This resulted in persistent infection and the virus could be detected in blood and urine for more than three months.…”

Section: Polyomavirus Infections (Jc)mentioning

confidence: 99%

Viral infections in mice with reconstituted human immune system components

Münz

2014

Immunology Letters

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Pathogenic viruses are often difficult to study due to their exclusive tropism for humans. The development of mice with human immune system components opens the possibility to study those human pathogens with a tropism for the human hematopoietic lineage in vivo. These include HCMV, EBV, KSHV, HIV, HTLV-1, dengue virus and JC virus. Furthermore, some human pathogens, like HSV-2, adenovirus, HCV, HBV and influenza A virus, with an additional tropism for somatic mouse tissues or for additional transplanted human tissues, mainly liver, have been explored in these models. The cellular tropism of these viruses, their associated diseases and primarily cell-mediated immune responses to these viral infections will be discussed in this review. Already some exciting information has been gained from these novel chimeric in vivo models and future avenues to gain more insights into the pathology, but also potential therapies, will be outlined. Although the respective in vivo models of human immune responses can still be significantly improved, they already provide preclinical systems for in vivo studies of important viral pathogens of humans. AbstractPathogenic viruses are often difficult to study due to their exclusive tropism for humans. The development of mice with human immune system components opens the possibility to study those human pathogens with a tropism for the human hematopoietic lineage in vivo. These include HCMV, EBV, KSHV, HIV, HTLV-1, dengue virus and JC virus. Furthermore, some human pathogens, like HSV-2, adenovirus, HCV, HBV and influenza A virus, with an additional tropism for somatic mouse tissues or for additional transplanted human tissues, mainly liver, have been explored in these models. The cellular tropism of these viruses, their associated diseases and primarily cell-mediated immune responses to these viral infections will be discussed in this review. Already some exciting information has been gained from these novel chimeric in vivo models and future avenues to gain more insights into the pathology, but also potential therapies, will be outlined. Although the respective in vivo models of human immune responses can still be significantly improved, they already provide preclinical systems for in vivo studies of important viral pathogens of humans.Christian Münz 3 Mice with reconstituted human immune system components as models of human immune responsesHuman immune responses can be studied in a correlative fashion in only a few tissues, which can be biopsied from patients or healthy individuals, including peripheral blood, some secondary lymphoid tissues, like tonsils, and the tumor microenvironment, assessing tumor infiltrating lymphocytes (TILs). For a more systematic analysis and in order to study the outcome of manipulations during immune responses, immunologists have primarily turned to the mouse as an in vivo animal model of mammalian immune responses. However, with a more and more detailed analysis of the mouse immune system it has become apparent that significant differences in ...

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“…Thereafter, JCPyV asymptomatically persists in renourinary tract and is intermittently shed into the urine (2)(3)(4). In immunocompromised patients, JCPyV can cause progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the brain, with typically fatal outcome (5,6). PML results from lytic JCPyV replication in subcortical oligodendrocytes that generate neuronal myelin sheaths.…”

mentioning

confidence: 99%

“…PML results from lytic JCPyV replication in subcortical oligodendrocytes that generate neuronal myelin sheaths. Progressive demyelination followed by neuronal dysfunction and cell death underlies the radiological and clinical features of PML (1,5,6). Despite some promising in vitro data (7), there is currently no specific antiviral therapy, and the outcome of PML depends largely on mounting JCPyV-specific immune functions that suppress JCPyV replication (1,6,8,9).…”

mentioning

confidence: 99%

Inter- and Intralaboratory Comparison of JC Polyomavirus Antibody Testing Using Two Different Virus-Like Particle-Based Assays

Kardas

Sadeghi

Weissbach

et al. 2014

Clin Vaccine Immunol

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e JC polyomavirus (JCPyV) can cause progressive multifocal leukoencephalopathy (PML), a debilitating, often fatal brain disease in immunocompromised patients. JCPyV-seropositive multiple sclerosis (MS) patients treated with natalizumab have a 2-to 10-fold increased risk of developing PML. Therefore, JCPyV serology has been recommended for PML risk stratification. However, different antibody tests may not be equivalent. To study intra-and interlaboratory variability, sera from 398 healthy blood donors were compared in 4 independent enzyme-linked immunoassay (ELISA) measurements generating >1,592 data points. Three data sets (Basel1, Basel2, and Basel3) used the same basic protocol but different JCPyV virus-like particle (VLP) preparations and introduced normalization to a reference serum. The data sets were also compared with an independent method using biotinylated VLPs (Helsinki1). VLP preadsorption reducing >35% activity was used to identify seropositive sera. The results indicated that Basel1, Basel2, Basel3, and Helsinki1 were similar regarding overall data distribution (P ‫؍‬ 0.79) and seroprevalence (58.0, 54.5, 54.8, and 53.5%, respectively; P ‫؍‬ 0.95). However, intra-assay intralaboratory comparison yielded 3.7% to 12% discordant results, most of which were close to the cutoff (0.080 < optical density [OD] < 0.250) according to Bland-Altman analysis. Introduction of normalization improved overall performance and reduced discordance. The interlaboratory interassay comparison between Basel3 and Helsinki1 revealed only 15 discordant results, 14 (93%) of which were close to the cutoff. Preadsorption identified specificities of 99.44% and 97.78% and sensitivities of 99.54% and 95.87% for Basel3 and Helsinki1, respectively. Thus, normalization to a preferably WHO-approved reference serum, duplicate testing, and preadsorption for samples around the cutoff may be necessary for reliable JCPyV serology and PML risk stratification.

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Detection of JC Virus-Specific Immune Responses in a Novel Humanized Mouse Model

Cited by 30 publications

References 27 publications

The Human Fetal Glial Cell Line SVG p12 Contains Infectious BK Polyomavirus

The Human Fetal Glial Cell Line SVG p12 Contains Infectious BK Polyomavirus

Viral infections in mice with reconstituted human immune system components

Inter- and Intralaboratory Comparison of JC Polyomavirus Antibody Testing Using Two Different Virus-Like Particle-Based Assays

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