Biological activities of a synthetic peptide composed of two unlinked domains from a retroviral transmembrane protein sequence.
We report several biological activities of a synthetic peptide whose sequence contains the highly conserved region of feline leukemia virus transmembrane protein (TM) synthetically linked to another short TM-derived sequence particularly rich in polar positive residues. This 29-amino-acid peptide blocked [3H]thymidine uptake 30 to 50% by concanavalin A-stimulated CD4(+)--but not CD8(+)-enriched murine splenocytes. Maximal suppression was detected at 12.5 micrograms (3 microM) to 75 micrograms (19 microM) per ml of growth medium; stimulation of [3H]thymidine uptake was observed at higher peptide concentrations. The synthetic peptide inhibited but did not stimulate [3H]thymidine uptake by mitogen-activated thymocytes and antibody production by splenocytes as determined in a liquid hemolytic plaque assay. Similarities are reported between a consensus sequence of diverse retroviral TMs and a region of alpha interferons shown by others to be important for antiviral and cytostatic properties. The TM sequence-derived synthetic peptide blocked in a nontoxic and sequence-specific manner the release of murine leukemia virus from two chronically infected cell lines. We suggest that some of the biological effects of retroviral TM are mediated through a common pathway shared with alpha interferons.
Wegemer
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DE
R. W. Johnson Pharmaceutical Research Institute, San Diego, California 92121.
Kabat
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Kloetzer
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D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D002460:Cell Line; D006462:Hemolytic Plaque Technique; D007166:Immunosuppressive Agents; D007370:Interferon Type I; D005256:Leukemia Virus, Feline; D009052:Leukemia Virus, Murine / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology*; D012191:Retroviridae Proteins / Q000494:pharmacology*; D012689:Sequence Homology, Nucleic Acid; D013936:Thymidine / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000494:pharmacology*
D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D007370:Interferon Type I; D010455:Peptides; D012191:Retroviridae Proteins; D014763:Viral Matrix Proteins; C063530:Ala-Lys-Leu-Arg-Glu-Arg-Leu-Lys-Gln-Arg-Gln-Gln-Leu-Gln-Asn-Arg-Arg-Gly-Leu-Asp-Ile-Leu-Phe-Leu-Gln-Glu-Gly-Gly-Leu; D013936:Thymidine