title: Complement opsonization of HIV-1 enhances the uptake by dendritic cells and involves the endocytic lectin and integrin receptor families.
abstract: Interaction with the complement system is an underappreciated aspect of HIV-1 infection; even in primary infection, complement fragments are found on virions with potential to affect the interplay between the virus and dendritic cells (DC). Since opsonization may affect the efficiency of uptake and the type of receptors utilized, we compared the interactions of DC with free HIV-1 (F-HIV) and complement opsonized HIV-1 (C-HIV). We demonstrate that C-HIV significantly enhanced the uptake by immature DC (IDC) and mature DC (MDC) and that the internalization rate was dependent on both opsonization of the virus and DC maturation state. Increased DC uptake of C-HIV was not due to opsonization related increased binding of virus to the surface of DC but rather increased internalization of C-HIV despite utilizing a similar repertoire of receptors as F-HIV. Both F-HIV and C-HIV interacted with C-type lectins, integrins, and CD4 and blocking these receptor families prevented HIV-1 from binding to DC at 4°C. Blocking integrins significantly reduced the binding and uptake of F-HIV and C-HIV implicating the involvement of several integrins such as β1-integrin, CR3, LFA-1, and α4β7. Distinctive for C-HIV was usage of β1-integrin and for F-HIV, usage of β7-integrin, whereas both F-HIV and C-HIV utilized both integrin chains of CR3. We have in this study identified the receptor types used by both F-HIV and C-HIV to bind to DC. Noteworthy, C-HIV was internalized more efficiently by DC than F-HIV, probably via receptor mediated endocytosis, which may entail different intracellular processing of the virus leading to both elevated infection and altered activation of HIV specific immune responses.
authors.affiliation: Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Veronica
authors.initials: V
authors.lastname: Tjomsland
authors.forename: Rada
authors.initials: R
authors.lastname: Ellegård
authors.forename: Karlhans
authors.initials: K
authors.lastname: Che
authors.forename: Jorma
authors.initials: J
authors.lastname: Hinkula
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Marie
authors.initials: M
authors.lastname: Larsson
mesh_terms: D015704:CD4 Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000821:virology; D004705:Endocytosis / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D007700:Kinetics; D037181:Lectins, C-Type / Q000378:metabolism*; D009895:Opsonin Proteins / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014771:Virion / Q000276:immunology; D053586:Virus Internalization
chemical_list: D015704:CD4 Antigens; D016023:Integrins; D037181:Lectins, C-Type; D009895:Opsonin Proteins; D011956:Receptors, Cell Surface; D003165:Complement System Proteins