Suppressive effect on polyclonal B-cell activation of a synthetic peptide homologous to a transmembrane component of oncogenic retroviruses.

Abstract

Purified feline leukemia virus, UV lightinactivated feline leukemia virus, and a synthetic peptide (CKS-17) homologous to a well-conserved region of the transmembrane components of several human and animal retroviruses were each studied for their effects on IgG production by feline peripheral blood lymphocytes. Using a reverse hemolytic plaque assay, both the viable virus and the UV-inactivated feline leukemia virus, but not the CKS-17, activated B lymphocytes to secrete IgG. When staphylococcal protein A, a polyclonal B-cell activator, was used to stimulate IgG synthesis by feline lymphocytes, the viable virus, the UV-inactivated virus, and the CKS-17 peptide each strongly suppressed IgG secretion without compromising viability of the lymphocytes. These findings suggest that the immunosuppressive influences of feline leukemia virus on immunoglobulin synthesis may reside in a conserved portion of the envelope glycoprotein that includes the region homologous to CKS-17.

Interleukin 10 is induced by recombinant HIV-1 Nef protein involving the calcium/calmodulin-dependent phosphodiesterase signal transduction pathway

“…A synthetic peptide homologous to a conserved domain of p15E, CKS-17, has been shown to be highly immunosuppressive in vitro and in vivo (39)(40)(41). CKS-17 down-regulates tumor necrosis factor-␣ and IL-12 and enhances IL-10 in vitro, suggesting that development of opportunistic infections and͞or progression of retrovirus-induced immunodeficiencies may not require intact replicating virus (30,42).…”

A Synthetic Peptide Homologous to Retroviral Transmembrane Envelope Proteins Depresses Protein Kinase C Mediated Lymphocyte Proliferation and Directly Inactivated Protein Kinase C: A Potential Mechanism for Immunosuppression

“…CKS-17-BSA has also been shown to inhibit the lytic activity of both freshly isolated and interferonby activated human monocytes (28), the polyclonal production of immunoglobulin by activated feline mononuclear cells (36), the production of interferon-7. by human mononuclear cells (42), and murine cytotoxic T lymphocyte activity (43).…”

Differential modulation of Th1- and Th2-related cytokine mRNA expression by a synthetic peptide homologous to a conserved domain within retroviral envelope protein.

“…We previously reported that UV-inactivated feline leukemia virus (3,5,15), HIV , SEA at 100 ng/ml (dotted bar), SEA at 100 ng/ml plus 30 ,LM MN50 (vertically striped bar), SEA at 100 ng/ml plus 30 ,uM MN21 (horizontally striped bar), or SEA at 100 ng/ml plus 30 ,uM MN21 plus anti-human IL-10 mAb (aIL-10) at 10 ,tg/ml (solid bar) for 5 hr. IFN-,y and IL-12 p40 heavy chain mRNA expressions were identified by RT-PCR.…”

“…Cianciolo et al (12) synthesized a heptadecapeptide, termed CKS-17, representing the conserved domain within this region. This peptide is immunosuppressive in vitro and in vivo and inhibits production of mediators-e.g., interferon y (IFN-'y), interleukin (IL)-2, and tumor necrosis factor a (12,(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26).…”