Specific association of retroviral envelope protein, p15E, with human cell surfaces

Kizaki, Tomohiko; Mitani, Masamitsu; Cianciolo, George J.; Ogasawara, Minoru; Good, Robert A.; Day, Noorbibi K.

doi:10.1016/0165-2478(91)90121-p

Cited by 6 publications

(4 citation statements)

References 24 publications

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“…In contrast, the expression of IL-2 and chemokine (C-X-C motif) ligand (CXCL-9, also called monokine induced by gamma interferon, MIG) decreased. Cell surface binding proteins, which possibly may represent receptors of the isu domain of gp41 and of p15E have been described [79][80][81][82][83][84][85]; however, it is unclear whether they function as such and whether they are involved in the signal transduction. Among the genes with the highest up-regulation were IL-6, matrix metalloproteinase 1 (MMP-1), triggering receptor expressed on myeloid cells 1 (TREM-1) and others.…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

The transmembrane proteins contribute to immunodeficiencies induced by HIV-1 and other retroviruses

Denner

2014

Aids

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Many microorganisms including retroviruses suppress the immune system of the infected host in order to maintain infection. Unfortunately, it is still unclear how retroviruses induce immunosuppression. There is increasing evidence of a common mechanism based on their transmembrane envelope proteins. This review therefore summarizes evidence of the involvement of the transmembrane envelope proteins in the immunopathogenesis of different retroviruses including HIV-1. Mutations in the immunosuppressive (isu) domain of the transmembrane envelope protein of several retroviruses abrogate the immunosuppressive activities in vitro and in vivo. Most importantly, virus sequences with such abrogating mutations were never found in HIV-1-infected individuals despite the fact that the mutated viruses are replication-competent. However, there is also evidence for additional, perhaps even divergent, strategies for each retrovirus. For example, in contrast to many other retroviruses, the HIV directly interacts with immune cells and infects them. In addition, HIV uses several accessory proteins to evade the immune response. Furthermore, the possible contribution of the transmembrane envelope proteins of endogenous retroviruses to immunosuppression when expressed on tumor cells or in the placenta is analyzed.

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Section: Mechanisms Of Actionmentioning

confidence: 99%

The transmembrane proteins contribute to immunodeficiencies induced by HIV-1 and other retroviruses

Denner

2014

Aids

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“…The mechanism how the ISU domain interacts with immune cells is still unclear. There are several reports showing binding of the TM proteins or synthetic peptides corresponding to the ISU domain to monocytes and B cells [ 64 – 68 ].…”

Section: Discussionmentioning

confidence: 99%

Absence of IL-10 production by human PBMCs co-cultivated with human cells expressing or secreting retroviral immunosuppressive domains

et al. 2018

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Immunosuppression by retroviruses including the human immunodeficiency virus—1 (HIV-1) is well known, however the mechanisms how retroviruses induce this immunosuppression is not fully investigated. It was shown that non-infectious retroviral particles as well as retroviral or recombinant retroviral transmembrane envelope (TM) proteins demonstrated immunosuppressive properties. The same was shown for peptides corresponding to a highly conserved domain in the TM protein. This domain is called immunosuppressive (ISU) domain and it induces modulation of the cytokine release of peripheral blood mononuclear cells (PBMCs) from healthy donors. In addition, it changes the gene expression of these cells. Common indications for the immunosuppressive activity were tumour growth in vivo and interleukin—10 (IL-10) release from human PBMCs in vitro. Single mutations in the ISU domain abrogated the immunosuppressive activity. In order to develop a new model system for the expression of the ISU domain and presentation to PBMCs which is not prone to possible endotoxin contaminations, two expression systems were developed. In the first system, designated pOUT, retroviral proteins containing the ISU domain were expressed and released into the cell culture medium, and in the second system, tANCHOR, the ISU domain was presented by a tetraspanin-anchored sequence on the cell surface of human cells. Both systems were exploited to express the wild-type (wt) ISU domains of HIV-1, of the porcine endogenous retrovirus (PERV) and of the murine leukaemia virus (MuLV) as well as to express mutants (mut) of these ISU domains. PERV is of special interest in the context of virus safety of xenotransplantation using pig organs. Expression of the TM proteins was demonstrated by confocal laser scanning microscopy, ELISA and Western blot analyses using specific antibodies. However, when cells expressing and releasing the ISU were co-incubated with human PBMCs, no increased production of IL-10 was observed when compared with the mutants. Similar results were obtained when the released TM proteins were concentrated by immunoprecipitation and added to PBMCs. We suggest that the absence of IL-10 induction can be explained by a low amount of protein, by the lack of a biologically active conformation or the absence of additional factors.

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“…Possible interpretation of the present observations is that MN21 activates adenylate cyclase through a receptor that couples it to G proteins. Although pl5E has been shown to directly bind to surfaces of human cells (33), a receptor for CKS- 17 has not yet been demonstrated. Another mechanism would be that internalized MN21 activates adenylate cyclase directly.…”

Section: Methodsmentioning

confidence: 99%

Induction of intracellular cAMP by a synthetic retroviral envelope peptide: a possible mechanism of immunopathogenesis in retroviral infections.

Haraguchi

Good

James-Yarish

et al. 1995

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

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A synthetic heptadecapeptide, CKS-17, represents the highly conserved amino acid sequences occurring within the transmembrane envelope protein of many animal and human retroviruses. CKS-17 has been demonstrated to exhibit suppressive properties for numerous immune functions. We have recently shown that CKS-17 acts as an immunomodulatory epitope causing an imbalance of human type 1 and type 2 cytokine production and suppression of cellmediated immunities. cAMP, an intracellular second messenger, plays an important role in regulation of cytokine biosynthesis-i.e., elevation of intracellular cAMP levels selectively inhibits type 1 cytokine production but has no effect or enhances type 2 cytokine production. Here, we demonstrate that CKS-17 induces dramatic rises in the intracellular cAMP levels of a human monocyte cell line and of human peripheral blood mononuclear cells in a time-and dose-dependent manner. A peptide corresponding to the reverse sequence of CKS-17, used as control, has no effect on intracellular cAMP levels. The cAMP-inducing ability of CKS-17 is significantly blocked by SQ-22536, an inhibitor of adenylate cyclase. These results indicate that CKS-17, a highly conserved component of the transmembrane proteins of immunosuppressive retroviruses, induces increased intracellular levels of cAMP via activation of adenylate cyclase and suggest that this retroviral envelope peptide may differentially modulate type 1 and type 2 cytokine production through elevation of intracellular cAMP levels.

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Specific association of retroviral envelope protein, p15E, with human cell surfaces

Cited by 6 publications

References 24 publications

The transmembrane proteins contribute to immunodeficiencies induced by HIV-1 and other retroviruses

The transmembrane proteins contribute to immunodeficiencies induced by HIV-1 and other retroviruses

Absence of IL-10 production by human PBMCs co-cultivated with human cells expressing or secreting retroviral immunosuppressive domains

Induction of intracellular cAMP by a synthetic retroviral envelope peptide: a possible mechanism of immunopathogenesis in retroviral infections.

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