Human T-Cell Leukemia Virus Type 1 (HTLV-1) p12<sup>I</sup>Down-Modulates ICAM-1 and -2 and Reduces Adherence of Natural Killer Cells, Thereby Protecting HTLV-1-Infected Primary CD4<sup>+</sup>T Cells from Autologous Natural Killer Cell-Mediated Cytotoxicity despite the Reduction of Major Histocompatibility Complex Class I Molecules on Infected Cells

Banerjee, Prabal; Feuer, Gerold; Barker, Edward

doi:10.1128/jvi.00887-07

Cited by 69 publications

(80 citation statements)

References 77 publications

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“…Defective NK cell function has been reported as a result of infection by a number of viruses, such as cytomegalovirus, hepatitis C virus, herpes simplex virus, human T-cell leukemia virus type 1, and HIV-1, as well as by other pathogens (8,17,22,33,50). NK cells from long-term nonprogressors and HIV-1-exposed seronegative individuals exhibited normal cytotoxic effector function (25,31,43), whereas rapid progression of diseases is associated with deregulation of NK cell phenotypes, leading to functional anergy and impaired lytic response (4,5,20).…”

Section: Discussionmentioning

confidence: 99%

Infection with Vpr-Positive Human Immunodeficiency Virus Type 1 Impairs NK Cell Function Indirectly through Cytokine Dysregulation of Infected Target Cells

Majumder

Venkatachari

O'Leary

et al. 2008

J Virol

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Section: Discussionmentioning

confidence: 99%

Infection with Vpr-Positive Human Immunodeficiency Virus Type 1 Impairs NK Cell Function Indirectly through Cytokine Dysregulation of Infected Target Cells

Majumder

Venkatachari

O'Leary

et al. 2008

J Virol

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“…Upon T-cell activation, p8 down-regulates proximal TCR signaling and causes T-cell anergy (8,9). Prior work has demonstrated that, although the orf-I protein products increase T-cell contact by lymphocyte function-associated antigen-1 (LFA-1) clustering (13), they also decrease interaction among T cells by downregulating intercellular adhesion molecule 1 (ICAM-1), ICAM-2, and the MHC-I at the cell surface to avoid recognition by natural killer (NK) cells and cytotoxic T cells (CTL) (14,15). Here we present data that reconcile these seemingly opposite effects of the p12 and p8 proteins on T cells.…”

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confidence: 99%

Human T-cell leukemia virus type 1 p8 protein increases cellular conduits and virus transmission

Prooyen

Gold

Andresen

et al. 2010

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

143

212

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The human T-cell leukemia virus type 1 (HTLV-1) is the cause of adult T-cell leukemia/lymphoma as well as tropical spastic paraparesis/ HTLV-1-associated myelopathy. HTLV-1 is transmitted to T cells through the virological synapse and by extracellular viral assemblies. Here, we uncovered an additional mechanism of virus transmission that is regulated by the HTLV-1-encoded p8 protein. We found that the p8 protein, known to anergize T cells, is also able to increase T-cell contact through lymphocyte function-associated antigen-1 clustering. In addition, p8 augments the number and length of cellular conduits among T cells and is transferred to neighboring T cells through these conduits. p8, by establishing a T-cell network, enhances the envelope-dependent transmission of HTLV-1. Thus, the ability of p8 to simultaneously anergize and cluster T cells, together with its induction of cellular conduits, secures virus propagation while avoiding the host's immune surveillance. This work identifies p8 as a viral target for the development of therapeutic strategies that may limit the expansion of infected cells in HTLV-1 carriers and decrease HTLV-1-associated morbidity.human leukemia retrovirus | orf-I

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“…30 In contrast, a recent study indicated that NK cells are unable to kill HTLV-1-infected primary CD4 ϩ T cells, in part due to a decreased ability of NK cells to adhere to HTLV-1-infected cells because of HTLV-1 p12(I)-mediated down-modulation of intercellular adhesion molecules 1 and 2. 32 It is also likely that CsA treatment limited the onset of the acquired immune response to HTLV-1 infection, as indicated by our serologic data from rabbits. We also demonstrated that CsA functionally impaired the ability of rabbits to immunologically respond to recall antigens such as tetanus toxoid and Jurkat T cells.…”

Section: Discussionmentioning

confidence: 81%

Cyclosporine-induced immune suppression alters establishment of HTLV-1 infection in a rabbit model

Haynes¹,

Ware²,

Premanandan³

et al. 2010

Blood

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IntroductionHuman T lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL)/lymphoma and is strongly associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and a variety of other immune-mediated disorders. 1-3 Despite a strong immune response against HTLV-1, the virus typically is maintained as a persistent infection throughout the lifetime of infected subjects. Critical immunologic parameters, including efficient cytotoxic T-cell responses against HTLV-1-expressing cells, determine viral loads throughout the course of infection and are linked to disease outcomes. 4,5 There have been several reports focused on the effect of immune suppression on pathogenesis of HTLV-1 disease. 6-9 HTLV-1-infected patients who are concurrently treated with immunosuppressive drugs, typically for organ or bone marrow transplantation procedures, often exhibit an accelerated or altered course for the development of HTLV-1-associated diseases. [10][11][12][13] These patients typically receive drugs such as cyclosporine A (CsA) and tacrolimus (FK-506) to prevent organ graft rejection. There are limited reports of the effects of immune suppression on early HTLV-1 infection because of the lack of clinical materials and inability to simulate the initial exposure of HTLV-1 infection on humans.We have used the rabbit model of HTLV-1 infection, in part, because of the ease and consistency of transmission of the viral infection in this species. Rabbits have been used to confirm routes of transmission for the virus infection, monitor sequential immune responses against HTLV-1 infection, test vaccine approaches, and determine virus-host relationships during the course of infection. [14][15][16][17][18] Our current study reported in this work tested the effects of immune suppression on the early spread of HTLV-1 infection in an established rabbit model. New Zealand white rabbits were divided into groups and treated with 10 mg/kg CsA, 20 mg/kg CsA, or saline vehicle control before infection by intravenous inoculation of HTLV-1-infected rabbit cells. Another group of rabbits was treated with 20 mg/kg CsA 1 week after HTLV-1 infection. Plasma CsA concentrations were monitored to ensure that therapeutic concentrations of the drug were obtained during treatment periods. Immune suppression was monitored in the rabbits by measuring lymphocyte proliferation to a recall antigen and mitogen stimulation, as well as flow cytometry and hematologic analysis. HTLV-1 viral expression in rabbits was monitored by testing ex vivo lymphocyte HTLV-1 p19 production, serologic parameters, and proviral loads from peripheral blood lymphocyte cultures. CsA treatment before HTLV-1 infection enhanced early viral expression compared with untreated HTLV-1-infected rabbits, and did alter long-term viral expression parameters. However, CsA treatment 1 week after infection diminished HTLV-1 expression throughout the 10-week study course. Our data indicate that immunologic control during early virus exposure determine...

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Abstract: Although natural killer (NK) cell-mediated control of viral infections is well documented, very little is known

Cited by 69 publications

References 77 publications

Infection with Vpr-Positive Human Immunodeficiency Virus Type 1 Impairs NK Cell Function Indirectly through Cytokine Dysregulation of Infected Target Cells

Infection with Vpr-Positive Human Immunodeficiency Virus Type 1 Impairs NK Cell Function Indirectly through Cytokine Dysregulation of Infected Target Cells

Human T-cell leukemia virus type 1 p8 protein increases cellular conduits and virus transmission

Cyclosporine-induced immune suppression alters establishment of HTLV-1 infection in a rabbit model

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