Immunosuppressive retroviral peptides: Immunopathological implications for immunosuppressive influences of retroviral infections

Haraguchi, Soichi; Good, Robert A.; Cianciolo, George J.; Engelman, Robert W.; Day, Noorbibi K.

doi:10.1002/jlb.61.6.654

Cited by 64 publications

(44 citation statements)

References 105 publications

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“…Previously we and others have reported that CKS-17 primarily down-regulates Th1-type immune response, including inhibition of IL-12 production (reviewed in Ref. 8).…”

Section: Discussionmentioning

confidence: 99%

“…One highly conserved region of the transmembrane proteins contains a leucine zipper-like domain comprising an ␣ helical secondary structure that may play an important role in the processes of virus fusion, infectivity, and entry (4 -7). Of interest, this leucine zipper-like domain overlaps a unique region that has strong immunosuppressive potential (5,7,8). CKS-17, a synthetic peptide, represents the prototypic amino acid sequence of this immunosuppressive domain (9) and has been found to exhibit potent immunosuppressive activities in numerous immune reactions both in vitro and in vivo (reviewed in Ref.…”

mentioning

confidence: 99%

“…CKS-17, a synthetic peptide, represents the prototypic amino acid sequence of this immunosuppressive domain (9) and has been found to exhibit potent immunosuppressive activities in numerous immune reactions both in vitro and in vivo (reviewed in Ref. 8).…”

mentioning

confidence: 99%

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A Retroviral-Derived Immunosuppressive Peptide Activates Mitogen-Activated Protein Kinases

Takahashi

Day

Luangwedchakarn

et al. 2001

The Journal of Immunology

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The highly conserved region within the retroviral transmembrane envelope proteins has been implicated in a number of retrovirus-associated mechanisms of immunosuppression. CKS-17, a synthetic peptide representing the prototypic sequence of the immunosuppressive domain, has been found to suppress numerous immune functions, disregulate cytokines, and elevate intracellular cAMP. In this report we show that using a human monocytic cell line THP-1, CKS-17 activates mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase 1 and 2 (ERK1/2). Kinetic studies show that CKS-17 induces an acute increase of ERK1/2 activity followed by a rapid decrease and then a second sustained increase of ERK1/2. CKS-17 also activates MAP kinase/ERK kinase (MEK) with a similar induction pattern. Mutant THP-1 cells isolated in our laboratory, in which CKS-17 exclusively fails to activate cAMP, did not show the transient decrease of CKS-17-induced ERK1/2 phosphorylation. Pretreatment of THP-1 cells or mutant THP-1 cells with cAMP analog or forskolin followed by treatment with CKS-17 showed no activation of MEK or ERK1/2. These results indicate that CKS-17 activates the MEK/ERK cascade and that there is a cross-talk between CKS-17-mediated MEK/ERK cascade and cAMP in that the MEK/ERK cascade is negatively regulated by cAMP. These data present a novel molecular mechanism(s) by this highly conserved retroviral immunosuppressive component.

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“…Previously we and others have reported that CKS-17 primarily down-regulates Th1-type immune response, including inhibition of IL-12 production (reviewed in Ref. 8).…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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A Retroviral-Derived Immunosuppressive Peptide Activates Mitogen-Activated Protein Kinases

Takahashi

Day

Luangwedchakarn

et al. 2001

The Journal of Immunology

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“…The endogenous MuLV envelope protein may retard the immune aggression to cells rather than accelerating the onset of IDDM. Since the same amino acid sequences suppressing the cellular immunity were located in our MuLV envelope protein [41,42], our endogenous MuLV envelope protein would reduce the cellular immunity against cell [29]. In fact, the long duration of insulitic stage before onset of IDDM and high expression of MuLV envelope gene during this stage suggests the existence of immune suppression.…”

Section: Discussionmentioning

confidence: 98%

“…However, more elaborate CTL analysis using MIN6N8a-primed CD8+ T cell isolated from draining lymph nodes should be carried out before getting a conclusion that MuLV envelope protein is not an autoantigen involved in the pathogenesis of NOD mouse IDDM. Since it was reported that retroviral envelope protein had the immune suppressive activity [29], our recombinant 3-2 envelope protein possibly downregulates the capability for cellular proliferation of NOD T cell in T cell proliferation assay.…”

Section: Discussionmentioning

confidence: 99%

Endogenous Ecotropic Murine Leukemia Viral (MuLV) Envelope Protein as a New Autoantigen Reactive with Non-obese Diabetic Mice Sera

Choi

Kim

et al. 2000

Journal of Autoimmunity

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Human endogenous retrovirus envelope proteins target dendritic cells to suppress T‐cell activation

et al. 2015

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Though mostly defective, human endogenous retroviruses (HERV)can retain open reading frames, which are especially expressed in the placenta. There, the envelope (env) proteins of HERV-W (Syncytin-1), HERV-FRD (Syncytin-2), and HERV-K (HML-2) were implicated in tolerance against the semi-allogenic fetus. Here, we show that the known HERV envbinding receptors ASCT-1 and -2 and MFSD2 are expressed by DCs and T-cells. When used as effectors in coculture systems, CHO cells transfected to express Syncytin-1, -2, or HML-2 did not affect T-cell expansion or overall LPS-driven phenotypic DC maturation, however, promoted release of IL-12 and TNF-α rather than IL-10. In contrast, HERV env expressing choriocarcinoma cell lines suppressed T-cell proliferation and LPS-induced TNF-α and IL-12 release, however, promoted IL-10 accumulation, indicating that these effects might not rely on HERV env interactions. However, DCs conditioned by choriocarcinoma, but also transgenic CHO cells failed to promote allogenic T-cell expansion. This was associated with a loss of DC/T-cell conjugate frequencies, impaired Ca 2+ mobilization, and aberrant patterning of f-actin and tyrosine phosphorylated proteins in T-cells. Altogether, these findings suggest that HERV env proteins target T-cell activation indirectly by modulating the stimulatory activity of DCs.Keywords: DCs r DC/T-cell conjugates r HERV r Immune tolerance r Immunological synapse r T-cell activation Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionHuman endogenous retroviruses (HERVs) are estimated to comprise about 8% of the human genome [1]. They are mainly germline transmitted. HERVs are typically defective as a result of multiple mutations in their genomes, and it is therefore only on exception that viral particles can be produced [1,2]. Endogenous retroviruses (ERVs) can substantially regulate host cell gene expression and functions. In addition to viral transcripts, ERV encoded proteins translated from intact ORFs were implicated Correspondence: Dr. Sibylle Schneider-Schaulies e-mail: s-s-s@vim.uni-wuerzburg.de in both pathological and physiological processes [3]. The latter has for instance been revealed for the envelope (env) regions of three HERVs (ERV-3, HERV-W, and HERV-FRD). These are highly expressed in early and late placentae, and their importance in successful accomplishment of pregnancy has been suggested [4][5][6][7][8][9][10], not least because spontaneous abortions or complications of gestation like preeclampsia are associated with reduced levels of HERV env proteins [11,12]. In fact, their expression has been found crucial in the intrauterine fetal development in promoting syncytiotrophoblast formation, while the HERV-FRD env was also associated with fetomaternal tolerance to prevent rejection of the fetus [13][14][15][16][17].Immunodeficiency is commonly associated with retroviral infections (for a recent review see [18] effector mechanisms studied, immunosuppressive domains (ISD) we...

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Immunosuppressive retroviral peptides: Immunopathological implications for immunosuppressive influences of retroviral infections

Abstract: Abstract:Studies ofthe

Cited by 64 publications

References 105 publications

A Retroviral-Derived Immunosuppressive Peptide Activates Mitogen-Activated Protein Kinases

A Retroviral-Derived Immunosuppressive Peptide Activates Mitogen-Activated Protein Kinases

Endogenous Ecotropic Murine Leukemia Viral (MuLV) Envelope Protein as a New Autoantigen Reactive with Non-obese Diabetic Mice Sera

Human endogenous retrovirus envelope proteins target dendritic cells to suppress T‐cell activation

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