Viral Modulation of T-Cell Receptor Signaling

Jerome, Keith R.

doi:10.1128/jvi.00059-08

Cited by 24 publications

(26 citation statements)

References 177 publications

(150 reference statements)

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“…Notably, we confirmed the previous finding (11) that HIV-1 Nef expression increased Lck accumulation in intracellular compartments ( Figure 3). Whether HIV-1 Nefs reduce or increase the responsiveness of virally infected T cells to stimulation is a matter of debate (11)(12)(13)(14)(15)(22)(23)(24)(25)(26). We found that HIV-1 Nef expression in infected PBLs did not alter or even slightly enhance late signaling events, as measured by IL-2 production upon stimulation.…”

Section: Discussionmentioning

confidence: 60%

“…Lymphotropic viruses also modulate the responsiveness of virally infected T cells to stimulation by interacting APCs in a manner that renders them more permissive for viral replication (12)(13)(14). HIV-1 and other primate lentiviruses manipulate the function of the IS and T cell activation mainly by means of the accessory multifunctional Nef protein, which also impairs MHC Ag presentation and enhances viral infectivity and replication (14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

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The inability to disrupt the immunological synapse between infected human T cells and APCs distinguishes HIV-1 from most other primate lentiviruses

Arhel

Lehmann

Clauß³

et al. 2009

J. Clin. Invest.

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Section: Discussionmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 99%

The inability to disrupt the immunological synapse between infected human T cells and APCs distinguishes HIV-1 from most other primate lentiviruses

Arhel

Lehmann

Clauß³

et al. 2009

J. Clin. Invest.

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“…Superficially, such infection might seem unimportant. However, for many viruses of both the lymphotropic and nonlymphotropic groups, emerging evidence shows that infection of T cells can disrupt or otherwise alter T-cell function (24). In the specific case of HSV infection, T cells very poorly support viral replication, but infection of T cells leads to inhibition of cytotoxic function and the skewing of cytokine synthesis toward an immunosuppressive phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…Whether other nonlymphotropic viruses utilize the VS and the degree to which VS-mediated infection is mechanistically distinct from the other pathways of entry by these viruses remain unanswered questions. Emerging evidence suggests that T cells can be infected by many nonlymphotropic viruses, and this infection can have profound influences on the function of T cells (24). If the VS proves to be widely used by many viruses, pharmacological targeting of the VS may provide a unique target to minimize T-cell infection and the concomitant immune modulatory effects.…”

Section: Discussionmentioning

confidence: 99%

“…In both cases after a 2-h incubation, T cells were removed, spun, washed with citrate buffer and from T-cell-induced apoptosis (2,26). In addition, certain viruses can modulate TCR signaling, either to prepare the T cell to itself support viral replication or to disarm antiviral mechanisms, thus ameliorating the threat posed by virus-reactive T cells (24).…”

Section: Discussionmentioning

confidence: 99%

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The Virological Synapse Facilitates Herpes Simplex Virus Entry into T Cells

Aubert

Yoon

Sloan

et al. 2009

J Virol

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The virological synapse (VS) is a specialized molecular structure that facilitates the transfer of certain lymphotropic viruses into uninfected T cells. However, the role of the VS in the transfer of nonlymphotropic viruses into T cells is unknown. Herpes simplex virus (HSV) has been shown in vitro to infect T cells and modulate T-cell receptor function, thereby suppressing T-cell antiviral function. However, whether such infection of T cells occurs in vivo is unknown. Here, we examined whether T-cell infection could be observed in human HSV disease and investigated the mechanism of HSV entry into T cells. We found that HSV-infected T cells were readily detectable during human disease, suggesting that infection and modulation of T-cell function plays a role in human immunopathology. HSV infection of both CD4؉ and CD8 The virological synapse (VS) is a specialized molecular structure that facilitates the transfer of certain lymphotropic viruses, such as human immunodeficiency virus (HIV) and human T-cell leukemia virus type 1 (HTLV-1), into uninfected T cells (22,28,38). Entry and infection of T cells by HIV or HTLV-1 via the VS is far more efficient than infection by cell-free virus, and thus this structure plays a critical role in the pathogenesis of these viruses. The organization of the VS is in many respects similar to the immunological synapse (IS), in particular, to the immature IS. The VS is highly enriched in the adhesion molecule lymphocyte function-associated antigen 1 (LFA-1) and its ligands intercellular adhesion molecule 1 (ICAM-1) and ICAM-3 (29); however, it does not possess the CD3-enriched central region associated with the mature IS (28,47). While the VS is critical to the pathogenesis of HIV and HTLV-1, it remains an unanswered question whether the VS is also involved in T-cell infection by other viruses, especially those not typically considered lymphotropic.Herpes simplex virus (HSV) is a remarkably successful human pathogen that establishes lifelong latency in neurons of the dorsal root ganglia. HSV can efficiently reactivate from the latent state and transmit to new hosts despite the presence of preformed immunity. HSV is thought to achieve this feat by employing a number of sophisticated immune evasion mechanisms (33), many of which are directed at the cellular arm of the immune response. In one such potential mechanism, HSV has evolved the ability to enter and infect T cells. Although T cells do not support efficient viral replication (25), infection by HSV profoundly modulates T-cell receptor (TCR) signaling, which prevents T-cell cytotoxic function (55) and alters cytokine production profiles toward an interleukin-10-dominated immunosuppressive phenotype (54). However, it is unknown whether and to what extent HSV infection of T cells occurs during human HSV disease. Furthermore, the dominant mechanisms by which HSV might gain access to lesion-infiltrating T cells have not been elucidated.Here, we evaluated T-cell infection during human HSV infections, the mechanisms by which HSV enters ...

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