A short polypeptide from the herpes simplex virus type 2 ICP10 gene can induce antigen aggregation and autophagosomal degradation for enhanced immune presentation.
It has been reported that certain polypeptides derived from aggregation-prone cellular proteins can turn soluble green fluorescent protein (GFP) into aggregates. Here we report our finding that a short peptide derived from a viral gene, ICP10 of herpes simplex virus (HSV)-2, also possesses such a property. A sequence as short as 13 amino acids from the middle region of the gene can convert GFP into an aggregation-prone toxic protein once it is fused to the C terminus. Moreover, this short peptide can direct a surrogate tumor antigen into the autophagosome/lysosome degradation pathway, drastically increasing both MHC class I and class II antigen presentation. The simultaneous induction of both arms of the T cell immune response to the tumor antigen effectively protects the immunized animals from tumor challenge. Designated VIPA (i.e., viral inducer of protein aggregation), this unique viral sequence may represent an attractive candidate as a molecular adjuvant for cancer immunotherapy and for other immunologically preventable diseases.
Fu
Xinping
X
Department of Biology and Biochemistry, University of Houston, TX 77204, USA.
Tao
Lihua
L
Zhang
Xiaoliu
X
D000818:Animals; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology; D001343:Autophagy; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D002522:Chlorocebus aethiops; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D018258:Herpesvirus 2, Human; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D010455:Peptides / Q000235:genetics / Q000276:immunology*; D010588:Phagosomes / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012264:Ribonucleotide Reductases / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014709:Vero Cells
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D010455:Peptides; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D010047:Ovalbumin; C100671:ICP10 protein, herpes simplex virus type 2; D012264:Ribonucleotide Reductases; D017346:Protein Serine-Threonine Kinases