title: Complement Opsonization Promotes Herpes Simplex Virus 2 Infection of Human Dendritic Cells.
abstract: Herpes simplex virus 2 (HSV-2) is one of the most common sexually transmitted infections globally, with a very high prevalence in many countries. During HSV-2 infection, viral particles become coated with complement proteins and antibodies, both present in genital fluids, which could influence the activation of immune responses. In genital mucosa, the primary target cells for HSV-2 infection are epithelial cells, but resident immune cells, such as dendritic cells (DCs), are also infected. DCs are the activators of the ensuing immune responses directed against HSV-2, and the aim of this study was to examine the effects opsonization of HSV-2, either with complement alone or with complement and antibodies, had on the infection of immature DCs and their ability to mount inflammatory and antiviral responses. Complement opsonization of HSV-2 enhanced both the direct infection of immature DCs and their production of new infectious viral particles. The enhanced infection required activation of the complement cascade and functional complement receptor 3. Furthermore, HSV-2 infection of DCs required endocytosis of viral particles and their delivery into an acid endosomal compartment. The presence of complement in combination with HSV-1- or HSV-2-specific antibodies more or less abolished HSV-2 infection of DCs. Our results clearly demonstrate the importance of studying HSV-2 infection under conditions that ensue in vivo, i.e., conditions under which the virions are covered in complement fragments and complement fragments and antibodies, as these shape the infection and the subsequent immune response and need to be further elucidated.
  
  
  
  During HSV-2 infection, viral particles should become coated with complement proteins and antibodies, both present in genital fluids, which could influence the activation of the immune responses. The dendritic cells are activators of the immune responses directed against HSV-2, and the aim of this study was to examine the effects of complement alone or complement and antibodies on HSV-2 infection of dendritic cells and their ability to mount inflammatory and antiviral responses. Our results demonstrate that the presence of antibodies and complement in the genital environment can influence HSV-2 infection under in vitro conditions that reflect the in vivo situation. We believe that our findings are highly relevant for the understanding of HSV-2 pathogenesis.
authors.affiliation: Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Elisa
authors.identifier: http://orcid.org/0000-0002-4235-8508
authors.initials: E
authors.lastname: Crisci
authors.affiliation: Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Rada
authors.initials: R
authors.lastname: Ellegård
authors.affiliation: Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Nyström
authors.affiliation: Division of Clinical Microbiology, Linköping University Hospital, Linköping, Sweden.
authors.forename: Elin
authors.initials: E
authors.lastname: Rondahl
authors.affiliation: Division of Infectious Diseases, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Serrander
authors.affiliation: Department of Infectious Disease, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Bergström
authors.affiliation: AIR Rheumatology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Christopher
authors.initials: C
authors.lastname: Sjöwall
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Eriksson
authors.affiliation: Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden marie.larsson@liu.se.
authors.forename: Marie
authors.initials: M
authors.lastname: Larsson
mesh_terms: D000914:Antibodies, Viral / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D006561:Herpes Simplex / Q000276:immunology; D018258:Herpesvirus 2, Human / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D009895:Opsonin Proteins / Q000276:immunology*; D014771:Virion / Q000378:metabolism
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D009895:Opsonin Proteins; D003165:Complement System Proteins