PMID- 28119397 OWN - NLM STAT- MEDLINE DCOM- 20170906 LR - 20191210 IS - 1530-6860 (Electronic) IS - 0892-6638 (Linking) VI - 31 IP - 4 DP - 2017 Apr TI - Misdirection of endosomal trafficking mediated by herpes simplex virus-encoded glycoprotein B. PG - 1650-1667 LID - 10.1096/fj.201600521R [doi] AB - Herpes simplex virus (HSV)-encoded glycoprotein B (gB) is the most abundant protein in the viral envelope and promotes fusion of the virus with the cellular membrane. In the present study, we found that gB impacts on the major histocompatibility complex (MHC)-II pathway of antigen presentation by fostering homotypic fusion of early endosomes and trapping MHC-II molecules in these altered endosomes. By using an overexpression approach, we demonstrated that transient expression of gB induces giant vesicles of early endosomal origin, which contained Rab5, early endosomal antigen 1 (EEA1), and large amounts of MHC-II molecules [human leukocyte antigen (HLA)-DR, and HLA-DM], but no CD63. In HSV-1-infected and stably transfected cell lines that expressed lower amounts of gB, giant endosomes were not observed, but strongly increased amounts of HLA-DR and HLA-DM were found in EEA1(+) early endosomes. We used these giant vesicles as a model system and revealed that gB interacts with Rab5 and EEA1, and that gB-induced homotypic fusion of early endosomes to giant endosomes requires phosphatidylinositol 3-phosphate, the activity of soluble N-ethylmaleimide-sensitive factor attachment protein receptors, and the cytosolic gB sequence (889)YTQVPN(894) We conclude that gB expression alters trafficking of molecules of the HLA-II processing pathway, which leads to increased retention of MHC-II molecules in early endosomal compartments, thereby intercepting antigen presentation.-Niazy, N., Temme, S., Bocuk, D., Giesen, C., Konig, A., Temme, N., Ziegfeld, A., Gregers, T. F., Bakke, O., Lang, T., Eis-Hubinger, A. M., Koch, N. Misdirection of endosomal trafficking mediated by herpes simplex virus-encoded glycoprotein B. CI - (c) FASEB. FAU - Niazy, Naima AU - Niazy N AD - Section of Immunobiology, Institute of Genetics, University of Bonn, Bonn, Germany. FAU - Temme, Sebastian AU - Temme S AD - Section of Immunobiology, Institute of Genetics, University of Bonn, Bonn, Germany; sebastian.Temme@uni-duesseldorf.de. FAU - Bocuk, Derya AU - Bocuk D AD - Section of Immunobiology, Institute of Genetics, University of Bonn, Bonn, Germany. FAU - Giesen, Carmen AU - Giesen C AD - Section of Immunobiology, Institute of Genetics, University of Bonn, Bonn, Germany. FAU - Konig, Angelika AU - Konig A AD - Section of Immunobiology, Institute of Genetics, University of Bonn, Bonn, Germany. FAU - Temme, Nadine AU - Temme N AD - Section of Immunobiology, Institute of Genetics, University of Bonn, Bonn, Germany. FAU - Ziegfeld, Angelique AU - Ziegfeld A AD - Section of Immunobiology, Institute of Genetics, University of Bonn, Bonn, Germany. FAU - Gregers, Tone F AU - Gregers TF AD - Department of Biosciences, University of Oslo, Oslo, Norway. FAU - Bakke, Oddmund AU - Bakke O AD - Department of Biosciences, University of Oslo, Oslo, Norway. FAU - Lang, Thorsten AU - Lang T AD - Membrane Biochemistry, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany. FAU - Eis-Hubinger, Anna M AU - Eis-Hubinger AM AD - Institute of Virology, University of Bonn Medical Centre, Bonn, Germany. FAU - Koch, Norbert AU - Koch N AD - Section of Immunobiology, Institute of Genetics, University of Bonn, Bonn, Germany. LA - eng PT - Journal Article DEP - 20170124 PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - 0 (HLA-D Antigens) RN - 0 (HLA-DM antigens) RN - 0 (HLA-DR Antigens) RN - 0 (Phosphatidylinositol Phosphates) RN - 0 (Tetraspanin 30) RN - 0 (Vesicular Transport Proteins) RN - 0 (Viral Envelope Proteins) RN - 0 (early endosome antigen 1) RN - 0 (glycoprotein B, Simplexvirus) RN - 0 (phosphatidylinositol 3-phosphate) RN - EC 3.6.1.- (RAB5C protein, human) RN - EC 3.6.5.2 (rab5 GTP-Binding Proteins) SB - IM MH - Amino Acid Motifs MH - Animals MH - COS Cells MH - Chlorocebus aethiops MH - Endosomes/*metabolism/virology MH - HLA-D Antigens/metabolism MH - HLA-DR Antigens/metabolism MH - HeLa Cells MH - Humans MH - Phosphatidylinositol Phosphates/metabolism MH - Protein Transport MH - Tetraspanin 30/metabolism MH - Vesicular Transport Proteins/metabolism MH - Viral Envelope Proteins/chemistry/genetics/*metabolism MH - rab5 GTP-Binding Proteins/metabolism OTO - NOTNLM OT - HLA class II OT - HSV-1 OT - antigen processing compartments OT - giant endosomal vesicles OT - signal sequences EDAT- 2017/01/26 06:00 MHDA- 2017/09/07 06:00 CRDT- 2017/01/26 06:00 PHST- 2016/08/13 00:00 [received] PHST- 2017/01/01 00:00 [accepted] PHST- 2017/01/26 06:00 [pubmed] PHST- 2017/09/07 06:00 [medline] PHST- 2017/01/26 06:00 [entrez] AID - fj.201600521R [pii] AID - 10.1096/fj.201600521R [doi] PST - ppublish SO - FASEB J. 2017 Apr;31(4):1650-1667. doi: 10.1096/fj.201600521R. Epub 2017 Jan 24.