Recombinant hydrophilic region of murine retroviral protein p15E inhibits stimulated T-lymphocyte proliferation.

Abstract

Retroviral envelope protein pl5E and antigenically related proteins have been implicated as potential mediators of immune dysfunction associated with retroviral infections and with neoplasia. Due to its extreme hydrophobicity, purified pl5E has not been available in a nondenatured form or in sufficient quantities for detailed studies on the mechanisms of its immunosuppressive effects. Therefore, a plasmid was constructed to direct the synthesis in Escherichia coli of the major hydrophilic region of murine pl5E. The purified recombinant piSE derivative, soluble under physiological conditions, inhibited by up to 60% (EC50 = 7.5 nM) the anti-CD3-driven proliferation of human T lymphocytes but had no effect on the proliferation of the transformed T-cell line Jurkat. The recombinant protein also inhibited, by up to an average of 92% (EC50 2.1 ,uM), the proliferation of the murine T-cell line CTLL-2. These data (i) provide direct evidence that a retroviral envelope protein can itself inhibit lymphoproliferative function and (ii) map the inhibitory activity to a specific region of pl5E. The availability of soluble, recombinant pl5E should facilitate studies of the pathogenesis of the immunosuppression accompanying retroviral infections and neoplastic diseases.

Depressed monocyte polarization and clustering of dendritic cells in patients with head and neck cancer: In vitro restoration of this immunosuppression by thymic hormones

“…The present findings support these earlier reports. It is known that the suppressive effects of pl5E-like factors and a 17-aminoacid peptide synthesized from the highly conserved region of MuLV pl5E (CKS-17) are not restricted to monocyte chemotaxis, but also have suppressive effects on monocyte-mediated killing by inactivating interleukin-1 (IL-1) [29,18], on the respiratory burst of human monocytes [20], on feline neutrophil activation [30], on the IL-2-or IL-1-dependent proliferation and the blastogenic responses to mitogens and allo-antigens of T cells [14,32,36,39,41] on the human natural killer cell activity of NK cells [21], on polyclonal B cell activation [33] and, more relevant to this report, on the clustering capability of dendritic cells [47]. It is likely that HNSCC-derived pl5E-like factors are also responsible for the impaired clustering capability of the HNSCC dendritic cells shown in the present report.…”

Identification, using synthetic peptides, of the minimum amino acid sequence from the retroviral transmembrane protein p15E required for inhibition of lymphoproliferation and its similarity to gp21 of human T-lymphotropic virus types I and II

“…However, in the mid-1970s, several laboratories demonstrated that inactivated retroviruses abrogated resistance to subsequent challenge infection (29,45). Additional studies of Cianciolo and Snyderman and colleagues (3,11,12,18,27,28,33) with synthetic peptides and a recombinant expression product of pl5E have demonstrated that the active sequence is contained within the viral transmembrane protein p15E. Computer-assisted analysis of the amino acid sequences of various animal retroviral transmembrane proteins as well as that of human T-lymphotropic virus types I and II (HTLV-I and -II) showed that a very high degree of similarity exists within a 26-amino-acid region (4).…”

Blockade of Type I Interferon (IFN) Production by Retroviral Replicating Vectors and Reduced Tumor Cell Responses to IFN Likely Contribute To Tumor Selectivity

“…The glyco-Gag (Pr80gag) expressed by retroviruses has shown to be incorporated into viral particles (29,30) and plays a role in inhibiting the function of APOBEC3 in target cells (31). In addition, an immunosuppressive peptide located in the TM subunit of several MLV envelope proteins has been described (32,33). To ask where the immunosuppressive component resides in the viral particles, 3 retroviral nonreplicating vectors pseudotyped with the amphotropic (MLV-A), VSV-G glycoprotein (MLV-G), or amphotropic envelope plus VSV-G glycoproteins (MLV-AϩG) that do not express glyco-Gag were generated.…”