Leukemia virus long terminal repeat activates NFκB pathway by a TLR3-dependent mechanism

Abujamra, Ana Lúcia; Spanjaard, Remco A.; Akinsheye, Idowu; Zhao, Xinzhen; Faller, Douglas V.; Ghosh, Santanu

doi:10.1016/j.virol.2005.10.003

Cited by 20 publications

(13 citation statements)

References 90 publications

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“…The p110α-H1047R protein is expressed in the 10T1/2 cells with the retroviral vector RCAS (35). It is therefore conceivable that the viral sequences of the vector could elicit an IFN response through recognition of double stranded RNA sequences of RCAS LTR by TLR3 (Toll-like receptor 3) or by Ddx58 (DEAD/H box polypeptide RIG-I) (36). In this case, PI3K activity would be irrelevant for the phosphorylation of Stat3.…”

Section: Resultsmentioning

confidence: 99%

Essential role of Stat3 in PI3K-induced oncogenic transformation

Hart¹,

Liao

Yates

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Cells transformed by the p110α-H1047R mutant of PI3K show increased tyrosine phosphorylation of Stat3. This activation of Stat3 is important for the transformation process, because a dominant-negative mutant of Stat3 interferes with PI3K-induced oncogenesis. GDC-0941, a specific inhibitor of PI3K reduces the level of Stat3 phosphorylation. The effect of PI3K on Stat3 appears to be mediated by a member of the Tec kinase family. The Tec kinase inhibitor LFM-A13 blocks Stat3 phosphorylation in H1047R-transformed cells. The Janus kinase inhibitor AG490 and the Src kinase inhibitor Src-1, as well as rapamycin, have no effect on Stat3 phosphorylation in H1047R-transformed cells. The H1047R-transformed cells also release a factor that induces Stat3 phosphorylation in normal cells with possible effects on the cellular microenvironment. In some human tumor cell lines, the enhanced phosphorylation of Stat3 is inhibited by both PI3K and by Tec kinase inhibitors, suggesting that the link between PI3K and Stat3 is significant in human cancer.

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Section: Resultsmentioning

confidence: 99%

Essential role of Stat3 in PI3K-induced oncogenic transformation

Hart¹,

Liao

Yates

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…A number of canine TLRs have also been detected by immunohistochemical staining and flow cytometry . The use of feline models for investigation of human diseases as diverse as type 2 diabetes mellitus and human immunodeficiency virus infection has yielded additional data on PRRs in cats, including the expression of functional TLRs by the endocrine pancreas and modulation of TLR signaling by retroviral pathogens . Enhanced expression of canine TLRs has been observed in clinical cases of osteoarthritis and cystic endometrial hyperplasia/pyometra; however, the majority of published research in dogs concerns the expression of PRRs in the intestinal tract, particularly in relation to inflammatory bowel disease (IBD) .…”

Section: Immunopathology Of Sepsismentioning

confidence: 99%

The Immunopathology of Sepsis: Pathogen Recognition, Systemic Inflammation, the Compensatory Anti‐Inflammatory Response, and Regulatory T Cells

Lewis

Chan

Pinheiro

et al. 2012

Veterinary Internal Medicne

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Sepsis, the systemic inflammatory response to infection, represents the major cause of death in critically ill veterinary patients. Whereas important advances in our understanding of the pathophysiology of this syndrome have been made, much remains to be elucidated. There is general agreement on the key interaction between pathogen‐associated molecular patterns and cells of the innate immune system, and the amplification of the host response generated by pro‐inflammatory cytokines. More recently, the concept of immunoparalysis in sepsis has also been advanced, together with an increasing recognition of the interplay between regulatory T cells and the innate immune response. However, the heterogeneous nature of this syndrome and the difficulty of modeling it in vitro or in vivo has both frustrated the advancement of new therapies and emphasized the continuing importance of patient‐based clinical research in this area of human and veterinary medicine.

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“…17 Some of these stimuli, like type I interferons 18 or murine retrovirus long terminal repeat, which has been shown to activate immune cells via Toll-like receptor-3 (TLR-3), 19 are present in vivo during an acute FV infection. We have investigated whether or not these stimuli can overcome the impairment in maturation of infected DCs.…”

Section: Fv Infection Interfered With Maturation Of Dcs But Not With mentioning

confidence: 99%

Friend retrovirus infection of myeloid dendritic cells impairs maturation, prolongs contact to naïve T cells, and favors expansion of regulatory T cells

Balkow

Krux

Loser

et al. 2007

Blood

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IntroductionDendritic cells (DCs) are the most potent antigen-presenting cells (APCs) of the immune system, and they are pivotal in the initiation of immune responses against viruses. 1 However, a number of viruses are able to infect DCs, and several recent studies have investigated the effect of such infections on the biology of DCs. Although only very few studies report enhanced or unchanged functions of DCs after viral infection, most viruses seem to impair functional properties of DCs (for review, see Pollara et al 2 ). These data imply that viruses infect DCs as a strategy of immune escape.In most reports that demonstrate the impairment of DCs by viruses, the morphology, phenotype, viability, and the ability to secrete cytokines of infected DCs was found to be altered, suggesting that viruses might have a significant impact on the DC-mediated initiation of an immune response in an infected host. 2 In fact, there is 1 report that directly shows that measles virus infection of DCs can result in unstable DC-T-cell contacts and, as a consequence, in impaired T-cell activation. 3 Retroviruses, such as HIV, are also known to infect DCs and interfere with their maturation. 4 Maturation of DCs can easily be measured by analyzing the expression of costimulatory molecules such as CD40, CD80, and CD86, or maturation markers like the molecule CD83. 5 However, the biological consequences of retrovirus infection of DCs for antigen presentation to T cells has not been investigated in detail so far. The most important functional properties of DCs are T-cell engagement and subsequent activation, which is the critical step in inducing adaptive immunity after infection. Since the interaction of DCs and naive T cells requires physical cell-cell contact, we used a 3D collagen matrix model 6 to investigate the contact duration and kinetics of virus-infected DCs with naive T cells. Friend virus (FV) is a retroviral complex comprised of 2 components: a replicationcompetent helper virus called Friend murine leukemia virus (F-MuLV), which is nonpathogenic in adult mice; and a replicationdefective but pathogenic component called spleen focus-forming virus (SFFV). 7 Coinfection of cells by the 2 viruses allows SFFV to spread by being packaged into F-MuLV-encoded virus particles. FV infection of susceptible adult mice induces polyclonal proliferation of erythroid precursor cells, causing severe splenomegaly. This proliferation is caused by the binding of the SFFV envelope glycoprotein to the erythropoietin receptors of nucleated erythroid cells. 8 In susceptible mice, FV subsequently transforms erythroid precursor cells, leading to fully malignant erythroleukemias. 9 However, beside erythroid precursor cells, FV can also infect a variety of other cells types, including B cells, monocytes, and granulocytes. 10 In addition, FV induces a severe generalized immunosuppression during acute infection 9,10 ; however, it is unknown whether this is the result of a functional impairment of APCs due to virus infection. Susceptibility to both FV-i...

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Leukemia virus long terminal repeat activates NFκB pathway by a TLR3-dependent mechanism

Cited by 20 publications

References 90 publications

Essential role of Stat3 in PI3K-induced oncogenic transformation

Essential role of Stat3 in PI3K-induced oncogenic transformation

The Immunopathology of Sepsis: Pathogen Recognition, Systemic Inflammation, the Compensatory Anti‐Inflammatory Response, and Regulatory T Cells

Friend retrovirus infection of myeloid dendritic cells impairs maturation, prolongs contact to naïve T cells, and favors expansion of regulatory T cells

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