Suppression of human lymphocyte mitogen response by proteins of the type‐D retrovirus PMFV

Denner, Joachim; Wunderlich, V.; Bierwolf, D

doi:10.1002/ijc.2910370221

Cited by 8 publications

(7 citation statements)

References 17 publications

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“…Among the plethora of effector mechanisms studied, immunosuppressive domains (ISD) were identified within the ectodomains of transmembrane env proteins of certain retroviruses, and a corresponding 17 aa synthetic peptide (CKS-17) was found to be immunosuppressive in vitro and in vivo [19,20]. The immunosuppression (ISU) activity of retroviral env proteins in vitro was often reflected by their ability to inhibit stimulated expansion of PBMCs or T-cells indicating that they might directly act on these targets [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Introductionmentioning

confidence: 99%

“…The immunosuppression (ISU) activity of retroviral env proteins in vitro was often reflected by their ability to inhibit stimulated expansion of PBMCs or T-cells indicating that they might directly act on these targets [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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“…Rec is analogous to the Rev protein of HIV-1 and when highly expressed has been shown to promote tumour development in mice [99,100]. A region of the transmembrane domain of env has been found to be immunosuppressive in several retroviruses—the so-called immunosuppressive domain [101–103]. Heidmann and co-workers showed that tumours expressing env proteins of mouse mammary tumour virus can escape the immune response (at least transiently), whereas tumours having knocked-out env genes were efficiently recognized by the immune system and rejected successfully [104].…”

Section: Molecular Basis Of a Possible Hk2 Connection With The Develomentioning

confidence: 99%

‘There and back again’: revisiting the pathophysiological roles of human endogenous retroviruses in the post-genomic era

Magiorkinis

Belshaw

Katzourakis

2013

Phil. Trans. R. Soc. B

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Almost 8% of the human genome comprises endogenous retroviruses (ERVs). While they have been shown to cause specific pathologies in animals, such as cancer, their association with disease in humans remains controversial. The limited evidence is partly due to the physical and bioethical restrictions surrounding the study of transposons in humans, coupled with the major experimental and bioinformatics challenges surrounding the association of ERVs with disease in general. Two biotechnological landmarks of the past decade provide us with unprecedented research artillery: (i) the ultra-fine sequencing of the human genome and (ii) the emergence of high-throughput sequencing technologies. Here, we critically assemble research about potential pathologies of ERVs in humans. We argue that the time is right to revisit the long-standing questions of human ERV pathogenesis within a robust and carefully structured framework that makes full use of genomic sequence data. We also pose two thought-provoking research questions on potential pathophysiological roles of ERVs with respect to immune escape and regulation.

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“…To date, all retrovirus isolates tested show some degree of immunosuppression in an inactivated state [55][56][57][58][59][60][61][62][63][64]. In general, most of these studies concentrate on T-lymphocyte function.…”

Section: [El V-associated Irnmunosuppressive Factors In Vitromentioning

confidence: 99%

Feline leukemia virus: current status of the feline induced immune depression and immunoprevention

Olsen

Lewis

Lafrado³

et al. 1987

Cancer Metast Rev

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This is a review of the current knowledge of feline leukemia virus (FeLV) associated with immune depression observed in cats. It will focus on the clinical and experimental observations associated with feline retroviral infection and presence in vivo and in vitro. We will briefly describe retroviral-associated acquired immune deficiency syndrome associated with FeLV infection in the cat and specific cellular pathology associated with FeLV latency. In addition, we will focus on the action of FeLV-p15E in vitro and describe possible mechanisms of the FeLV-associated immunosuppression observed both in vivo and in vitro. Lastly, we will evaluate the current status of immunoprevention of FeLV. We will not attempt an in-depth analysis of the current literature; our focus is to review current findings as they relate to feline AIDS and immunotherapy.

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Suppression of human lymphocyte mitogen response by proteins of the type‐D retrovirus PMFV

Cited by 8 publications

References 17 publications

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

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

‘There and back again’: revisiting the pathophysiological roles of human endogenous retroviruses in the post-genomic era

Feline leukemia virus: current status of the feline induced immune depression and immunoprevention

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