Binding of HSV-1 glycoprotein K (gK) to signal peptide peptidase (SPP) is required for virus infectivity.
Glycoprotein K (gK) is a virion envelope protein of herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), which plays important roles in virion entry, morphogenesis and egress. Two-hybrid and pull-down assays were utilized to demonstrate that gK and no other HSV-1 genes specifically binds to signal peptide peptidase (SPP), also known as minor histocompatibility antigen H13. SPP dominant negative mutants, shRNA against SPP significantly reduced HSV-1 replication in vitro. SPP also affected lysosomes and ER responses to HSV-1 infection. Thus, in this study we have shown for the first time that gK, despite its role in fusion and egress, is also involved in binding the cytoplasmic protein SPP. These results also suggest that SPP plays an important role in viral replication and possibly virus pathogenesis. This makes SPP unique in that its function appears to be required by the virus as no other protein can compensate its loss in terms of viral replication.
Center for Neurobiology and Vaccine Development, Ophthalmology Research, Department of Surgery, Los Angeles, California, United States of America.
Sariah J
SJ
Allen
Center for Neurobiology and Vaccine Development, Ophthalmology Research, Department of Surgery, Los Angeles, California, United States of America.
Kevin R
KR
Mott
Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Yoshiharu
Y
Matsuura
Department of Microbiology, Faculty of Medicine Yamanashi University, Yamanashi, Japan.
Kohji
K
Moriishi
Division of Biotechnology and Molecular Medicine, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, United States of America.
Konstantin G
KG
Kousoulas
Center for Neurobiology and Vaccine Development, Ophthalmology Research, Department of Surgery, Los Angeles, California, United States of America.
Homayon
H
Ghiasi
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D011485:Protein Binding; D034741:RNA, Small Interfering; D020798:Two-Hybrid System Techniques; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000235:genetics / Q000502:physiology
D034741:RNA, Small Interfering; C072448:UL53 protein, Human herpesvirus 1; D014764:Viral Proteins; D016282:Aspartic Acid Endopeptidases; C460085:signal peptide peptidase