Complement and antibodies: a dangerous liaison in HIV infection?

Due to ongoing recombination and mutations, HIV permanently escapes from neutralizing antibody (nAb) responses of the host. By the masking of epitopes or shedding of gp120, HIV-1 further impedes an efficient neutralization by Abs. Therefore, nAbs responses of the host are chasing behind a rapidly evolving virus and mainly non-neutralizing antibodies (non-nAbs) are present in the host. At the same time, complement deposition on immune-complexed HIV may counteract the immune response by enhancing the infection. On the other hand, complement-mediated lysis is a putative effector mechanism to control viral replication. Here we review the complex interplay between complement, neutralizing and non-neutralizing Abs during HIV infection and discuss the contribution of Abs and complement in blocking versus enhancing the course of infection.

HIV-1 induced generation of C5a attracts immature dendriticcells and promotes infection of autologous T cells.

For the recruitment of dendritic cells (DC) to the site of infection, DC express several sensors for danger signals, such as receptors for C5a. This anaphylatoxin is generated upon complement activation. As HIV-1 triggers the complement cascade, we determined whether C5a is generated by the virus and tested the functional activity of C5a in migration and infection assays. The immature (i)DC responded in migration assays to recombinant C5a and native C5a, which was generated in situ upon activation of the complement system by HIV-1. In combined migration and infection assays, a C5a-dependent enhancement of HIV-1 infection in DC-T cell cocultures was observed. These results indicate that HIV induces generation of C5a and thereby attracts iDC, which in turn promote the productive infection of autologous primary T cells.

Tracing complement-retroviral interactions from mucosal surfaces to the lymphatic tissue.

During (nearly) all steps in retroviral pathogenesis, viruses are confronted with complement and complement receptor (CR)-positive cells. As all of the retroviruses tested so far activate the complement system, members of this virus family have adapted different protection mechanisms to keep complement activation under the threshold necessary to avoid complement-mediated lysis. As a consequence of complement activation, retroviruses are covered with complement proteins and thus provide additional ligands to interact with CR-expressing cells. This review discusses the complex complement-retroviral interactions and follows the fate of the virus on its way to the lymphatic tissue.