Animal models for human T-lymphotropic virus type 1 (HTLV-1) infection and transformation

Lairmore, Michael Dale; Silverman, Lee; Ratner, Lee

doi:10.1038/sj.onc.1208974

Cited by 64 publications

(64 citation statements)

References 184 publications

(160 reference statements)

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“…The plasmids pc53-SN3 (expressing w.t. p53 through CMV promoter), pRc/CMV-p53 (residues 22 and 23), expressing the mutant p53 carrying point mutations at positions 22 . A set of plasmids expressing different clones of p53-specific siRNAs (MISSION TRC shRNA Target Set) was purchased from Sigma-Aldrich Corporation.…”

Section: Plasmids and Transient Transfectionmentioning

confidence: 99%

“…Tax is a potent oncoprotein capable of transforming cultured rodent cells and primary human T-lymphocytes 21 and of inducing tumors in transgenic animals. 22 This oncogenic potential is accounted for by Tax ability to modulate the synthesis or activity of many regulatory proteins which control a variety of fundamental processes in cells, like gene expression, cell cycle, apoptosis and genetic stability [for more details see recent reviews in Refs. 21,[23][24][25].…”

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confidence: 99%

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Retracted: Dose‐dependent dual effect of HTLV‐1 tax oncoprotein on p53‐dependent nucleotide excision repair in human T‐cells

Schavinsky-Khrapunsky¹,

Priel²,

Aboud³

2007

Intl Journal of Cancer

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In this study we investigated the effect of Tax on nucleotide excision repair (NER) in human T-cell lines by using the host cell repair analysis of UVC-irradiated reporter plasmid. This analysis revealed a p53-dpendent NER activity in wild type (w.t.) p53-containing T-cells and p53-independent NER in w.t. p53-lacking Tcells. Notably, in the w.t. p53-containing cells Tax exerted a dosedependent dual effect on NER. While low Tax doses markedly stimulated this repair, high Tax doses strongly reduced it. Further experiments demonstrated that the low Tax doses enhanced, in these cells, the level and the transcriptional function of their w.t. p53 protein. On the other hand, although the high Tax doses further increased the level of p53, they functionally inactivated its accumulating molecules. Both of these Tax effects on p53 proved to be mediated by Tax-induced NF-jB-related mechanisms. Together, these data suggest that by NF-jB activation Tax elevates the level of the cellular w.t. p53. However, while at low Tax doses the elevating w.t. p53 molecules are functionally active and capable of stimulating NER, intensifying further the NF-jB activation by the high Tax doses concomitantly evokes certain mechanism(s) which functionally inactivates the accumulating p53 protein. In contrast to this dual effect on the p53-dependent NER, Tax displayed only an inhibitory effect on the p53-independent NER by its high doses, whereas its low doses had no effect on this repair. The mechanisms of the NF-jB-associated effects on the level and function of the cellular w.t.p53 and of the p53-independent NER noted in our experimental systems are further investigated in our laboratory. ' 2007 Wiley-Liss, Inc.

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Section: Plasmids and Transient Transfectionmentioning

confidence: 99%

mentioning

confidence: 99%

Retracted: Dose‐dependent dual effect of HTLV‐1 tax oncoprotein on p53‐dependent nucleotide excision repair in human T‐cells

Schavinsky-Khrapunsky¹,

Priel²,

Aboud³

2007

Intl Journal of Cancer

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“…[28][29][30] One difficulty in the study of the biology of primary ATLL is that Tax expression occurs soon after cells are placed in tissue culture or murine models. 23,31 To better understand the mechanisms of malignant growth in ATLL, it is essential to study NF-B and its activation pathways independently of the effects of Tax in primary unmanipulated tumors.…”

Section: Introductionmentioning

confidence: 99%

IRF-4 and c-Rel expression in antiviral-resistant adult T-cell leukemia/lymphoma

Ramos¹,

Ruiz²,

Ratner

et al. 2006

Blood

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“…It is known that oral administration of this virus via infected lymphocytes can lead to seroconversion in animals. 21 Except for a single in vitro study devoted to epithelial cell infection by HTLV-1, 22 no attention has been paid to HTLV-1 interactions and passage across a tight enterocyte monolayer. It is known that DCs are susceptible to HTLV-1 infection by both cell-associated [23][24][25] and cell-free viruses 26,27 in vitro as well as in vivo and that they are able to transmit the infection to CD4 T cells, the main in vivo target of HTLV-1.…”

Section: Introductionmentioning

confidence: 99%

Transcytosis of HTLV-1 across a tight human epithelial barrier and infection of subepithelial dendritic cells

Martin‐Latil

Gnädig

Mallet

et al. 2012

Blood

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Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis. In addition to blood transfusion and sexual transmission, HTLV-1 is transmitted mainly through prolonged breastfeeding, and such infection represents a major risk for the development of adult T-cell leukemia/lymphoma. Although HTLV-1-infected lymphocytes can be retrieved from maternal milk, the mechanisms of HTLV-1 transmission through the digestive tract remain unknown. In the present study, we assessed HTLV-1 transport across the epithelial barrier using an in vitro model. Our results show that the integrity of the epithelial barrier was maintained during coculture with HTLV-1-infected lymphocytes, because neither morphological nor functional alterations of the cell monolayer were observed. Enterocytes were not susceptible to HTLV-1 infection, but free infectious HTLV-1 virions could cross the epithelial barrier via a transcytosis mechanism.Such virions were able to infect productively human dendritic cells located beneath the epithelial barrier. Our data indicate that HTLV-1 crosses the tight epithelial barrier without disruption or infection of the epithelium to further infect target cells such as dendritic cells. The present study provides the first data pertaining to the mode of HTLV-1 transport across a tight epithelial barrier, as can occur during mother-to-child HTLV-1 transmission during breastfeeding. IntroductionApproximately 5-20 million persons worldwide are infected by the human retrovirus human T-cell leukemia virus type 1 (HTLV-1), 1 and this virus is the causative agent of severe adult T-cell leukemia/lymphoma 2 and inflammatory syndromes such as tropical spastic paraparesis/HTLV-1-associated myelopathy, a slowly progressing neurodegenerative disease that occurs in 0.5%-3% of infected persons. 3 HTLV-1 is transmitted via sexual intercourse, by transfusion with contaminated blood, and from mother to child. The latter constitutes 15%-25% of overall transmission, so it is a major method of viral spread. 4,5 Although intrauterine or perinatal transmission during birth cannot be excluded, breastfeeding is the main pathway of HTLV-1 transmission in highly endemic areas such as intertropical Africa, the Caribbean, or regions of South America. 6,7 Milk-borne transmission is supported by the presence of high levels of infected lymphocytes in maternal milk, 10 5 -10 7 of these being transferred to the child at each feed, 8,9 in addition to infected macrophages and breast epithelial cells. Furthermore, leukocytes in the breast milk remain viable after ingestion for up to 4 hours because of the buffering capacity of breast milk and the low acidity of the neonatal child's stomach. 10,11 The risk of transmission increases with the time that children are breastfed, especially when this exceeds 6 months. In addition to the duration of breastfeeding, the mother's age, Ab titers directed against HTLV-1 antigens, proviral load in the PBMCs and milk, a...

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Animal models for human T-lymphotropic virus type 1 (HTLV-1) infection and transformation

Cited by 64 publications

References 184 publications

Retracted: Dose‐dependent dual effect of HTLV‐1 tax oncoprotein on p53‐dependent nucleotide excision repair in human T‐cells

Retracted: Dose‐dependent dual effect of HTLV‐1 tax oncoprotein on p53‐dependent nucleotide excision repair in human T‐cells

IRF-4 and c-Rel expression in antiviral-resistant adult T-cell leukemia/lymphoma

Transcytosis of HTLV-1 across a tight human epithelial barrier and infection of subepithelial dendritic cells

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