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Retargeting Oncolytic Vesicular Stomatitis Virus to Human T-Cell Lymphotropic Virus Type 1-Associated Adult T-Cell Leukemia.

Betancourt D, Ramos JC, Barber GN - J. Virol. (2015)

Bottom Line: VSV-gp160G was further noted to be highly attenuated and did not replicate efficiently in or induce significant cell death of primary CD4(+) T cells.Importantly, VSV-gp160G effectively exerted potent oncolytic activity in patient-derived ATL transplanted into NSG mice and facilitated a significant survival benefit.This effect greatly reduced neurotoxic risk associated with VSV infection while still allowing VSV to effectively target ATL cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida, USA.

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Related in: MedlinePlus

Biodistribution of VSV-gp160G in NSG mice. (A) Naive NSG mice (n = 4) were injected with 106 PFU of VSV-XN2 or VSV-gp160G i.p. and, at the indicated time points, a mouse was sacrificed, and tissue homogenates were analyzed for the presence of VSV virions using standard plaque assay with HeLa CD4+ cells. (B) Histology hematoxylin-eosin-stained samples taken from a TLO-m1 bearing NSG mouse either mock infected or treated with 106 PFU of VSV-gp160G. Syncytia were detected at VSV-gp160G ATL sites (black arrows) 76 days after TLO-m1-luc inoculation. (C) VSV-gp160G in organ homogenates of a TLO-m1-luc-bearing mouse (from panel B) treated with VSV-gp160G.
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Figure 7: Biodistribution of VSV-gp160G in NSG mice. (A) Naive NSG mice (n = 4) were injected with 106 PFU of VSV-XN2 or VSV-gp160G i.p. and, at the indicated time points, a mouse was sacrificed, and tissue homogenates were analyzed for the presence of VSV virions using standard plaque assay with HeLa CD4+ cells. (B) Histology hematoxylin-eosin-stained samples taken from a TLO-m1 bearing NSG mouse either mock infected or treated with 106 PFU of VSV-gp160G. Syncytia were detected at VSV-gp160G ATL sites (black arrows) 76 days after TLO-m1-luc inoculation. (C) VSV-gp160G in organ homogenates of a TLO-m1-luc-bearing mouse (from panel B) treated with VSV-gp160G.

Mentions: To determine the biodistribution of both VSV-XN2 and VSV-gp160G in a naive NSG mouse model, 106 PFU of either virus were injected into the peritoneal cavity of individual mice on day 0, and then the mice (n = 4) were euthanized on days 1, 7, 14, and 21 postinfection. The presence of VSV in brain, lung, liver, and kidney was determined by plaque assay. Residual VSV-gp160G was only detectable in the kidney 1 day after inoculation. In contrast, VSV-XN2 grew to a considerable titer in the brain and kidneys of the mouse sacrificed on day 14, and the mouse exhibited symptoms consistent with VSV-mediated neurotoxicity (Fig. 7A).


Retargeting Oncolytic Vesicular Stomatitis Virus to Human T-Cell Lymphotropic Virus Type 1-Associated Adult T-Cell Leukemia.

Betancourt D, Ramos JC, Barber GN - J. Virol. (2015)

Biodistribution of VSV-gp160G in NSG mice. (A) Naive NSG mice (n = 4) were injected with 106 PFU of VSV-XN2 or VSV-gp160G i.p. and, at the indicated time points, a mouse was sacrificed, and tissue homogenates were analyzed for the presence of VSV virions using standard plaque assay with HeLa CD4+ cells. (B) Histology hematoxylin-eosin-stained samples taken from a TLO-m1 bearing NSG mouse either mock infected or treated with 106 PFU of VSV-gp160G. Syncytia were detected at VSV-gp160G ATL sites (black arrows) 76 days after TLO-m1-luc inoculation. (C) VSV-gp160G in organ homogenates of a TLO-m1-luc-bearing mouse (from panel B) treated with VSV-gp160G.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4645320&req=5

Figure 7: Biodistribution of VSV-gp160G in NSG mice. (A) Naive NSG mice (n = 4) were injected with 106 PFU of VSV-XN2 or VSV-gp160G i.p. and, at the indicated time points, a mouse was sacrificed, and tissue homogenates were analyzed for the presence of VSV virions using standard plaque assay with HeLa CD4+ cells. (B) Histology hematoxylin-eosin-stained samples taken from a TLO-m1 bearing NSG mouse either mock infected or treated with 106 PFU of VSV-gp160G. Syncytia were detected at VSV-gp160G ATL sites (black arrows) 76 days after TLO-m1-luc inoculation. (C) VSV-gp160G in organ homogenates of a TLO-m1-luc-bearing mouse (from panel B) treated with VSV-gp160G.
Mentions: To determine the biodistribution of both VSV-XN2 and VSV-gp160G in a naive NSG mouse model, 106 PFU of either virus were injected into the peritoneal cavity of individual mice on day 0, and then the mice (n = 4) were euthanized on days 1, 7, 14, and 21 postinfection. The presence of VSV in brain, lung, liver, and kidney was determined by plaque assay. Residual VSV-gp160G was only detectable in the kidney 1 day after inoculation. In contrast, VSV-XN2 grew to a considerable titer in the brain and kidneys of the mouse sacrificed on day 14, and the mouse exhibited symptoms consistent with VSV-mediated neurotoxicity (Fig. 7A).

Bottom Line: VSV-gp160G was further noted to be highly attenuated and did not replicate efficiently in or induce significant cell death of primary CD4(+) T cells.Importantly, VSV-gp160G effectively exerted potent oncolytic activity in patient-derived ATL transplanted into NSG mice and facilitated a significant survival benefit.This effect greatly reduced neurotoxic risk associated with VSV infection while still allowing VSV to effectively target ATL cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida, USA.

Show MeSH
Related in: MedlinePlus