title: GP96 interacts with HHV-6 during viral entry and directs it for cellular degradation.
abstract: CD46 and CD134 mediate attachment of Human Herpesvirus 6A (HHV-6A) and HHV-6B to host cell, respectively. But many cell types interfere with viral infection through rapid degradation of viral DNA. Hence, not all cells expressing these receptors are permissive to HHV-6 DNA replication and production of infective virions suggesting the involvement of additional factors that influence HHV-6 propagation. Here, we used a proteomics approach to identify other host cell proteins necessary for HHV-6 binding and entry. We found host cell chaperone protein GP96 to interact with HHV-6A and HHV-6B and to interfere with virus propagation within the host cell. In human peripheral blood mononuclear cells (PBMCs), GP96 is transported to the cell surface upon infection with HHV-6 and interacts with HHV-6A and -6B through its C-terminal end. Suppression of GP96 expression decreased initial viral binding but increased viral DNA replication. Transient expression of human GP96 allowed HHV-6 entry into CHO-K1 cells even in the absence of CD46. Thus, our results suggest an important role for GP96 during HHV-6 infection, which possibly supports the cellular degradation of the virus.
authors.affiliation: Biocenter, Chair of Microbiology, University of Würzburg, 97074 Würzburg, Germany.
authors.forename: Bhupesh K
authors.initials: BK
authors.lastname: Prusty
authors.affiliation: Biocenter, Chair of Microbiology, University of Würzburg, 97074 Würzburg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Siegl
authors.affiliation: Biocenter, Chair of Microbiology, University of Würzburg, 97074 Würzburg, Germany.
authors.forename: Nitish
authors.initials: N
authors.lastname: Gulve
authors.affiliation: Graduate School of Medicine, Kobe University, Kobe 650-0017, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Mori
authors.affiliation: Biocenter, Chair of Microbiology, University of Würzburg, 97074 Würzburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rudel
mesh_terms: D000818:Animals; D016466:CHO Cells; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004279:DNA, Viral / Q000378:metabolism; D006367:HeLa Cells; D015654:Herpesvirus 6, Human / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D015151:Immunoblotting; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D051916:Membrane Cofactor Protein / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D008954:Models, Biological; D011485:Protein Binding; D059748:Proteolysis; D034622:RNA Interference; D014764:Viral Proteins / Q000378:metabolism*; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: D004279:DNA, Viral; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D014764:Viral Proteins; C053387:endoplasmin