title: Role of complement in the control of HIV dynamics and pathogenesis.
abstract: In all ex vivo preparations of HIV tested so far, C3 fragments and, after seroconversion, antibodies were detected on the viral surface. This indicates that HIV survives complement-mediated lysis. The virus has adopted different protection mechanisms to keep complement activation under the threshold necessary to induce virolysis. Among them are complement regulatory proteins that remain functionally active on the surface of HIV and turn down the complement cascade and serum proteins with complement regulatory activities. Therefore, opsonized virions accumulate in HIV-infected individuals, and subsequently adhere to complement receptor (CR) expressing cells. Among them are B cells, which bind opsonized virus. Such bound virus is efficiently transferred to autologous T cells, which subsequently are infected. Other cells interacting via CR with opsonized HIV are follicular dendritic cells (FDC). As shown by ex vivo experiments, up to 80% of virus is bound to follicular dendritic cells through C3-CR interactions. In the brain, HIV is not only interacting with complement proteins, but is able to induce their expression. Thus, interaction of HIV with the complement system is a main mechanism for pathogenesis to AIDS, since retention of (complement-resistant) opsonized viral particles on cell surfaces via CRs occurs in different compartments in HIV-infected individuals, thereby promoting transmission of virus to other permissive cells.
authors.affiliation: Institute of Hygiene and Social Medicine and Ludwig Boltzmann Institute for AIDS Research, University Innsbruck, Fritz Pregl-Strasse 3, A-6020 Innsbruck, Austria. heribert.stoiber@uibk.ac.at
authors.forename: Heribert
authors.initials: H
authors.lastname: Stoiber
authors.forename: Cornelia
authors.initials: C
authors.lastname: Speth
authors.forename: Manfred P
authors.initials: MP
authors.lastname: Dierich
mesh_terms: D000706:Anaphylatoxins / Q000502:physiology; D003167:Complement Activation; D003165:Complement System Proteins / Q000502:physiology*; D015658:HIV Infections / Q000209:etiology*; D006801:Humans
chemical_list: D000706:Anaphylatoxins; D003165:Complement System Proteins