Complement in different stages of HIV infection and pathogenesis.

The complement system is one of the most important weapons of innate immunity and is involved in all infectious processes. It is not only a mechanism for direct protection against an invading pathogen but it also interacts with the adaptive immunity to optimize the pathogen-specific humoral and cellular defence cascade in the body. One of the greatest challenges for the complement system is infection by HIV with its chronic course and sequential destruction of immune cells and immune organs. Due to its dual role as direct effector and as fine tuner of adaptive immunity, we focussed on complement in this review and analysed in detail the contribution of complement to the antiviral defence and to HIV pathogenesis on the one hand and the complement evasion strategies of the virus on the other hand. In the present review, this interplay between complement and the virus is illuminated for the three different stages of HIV pathogenesis and for events during therapy: (1) the acute infection process with the early events in mucosa and serum; (2) the asymptomatic stage with the complex interplay between complement-induced lysis and viral evasion strategies; (3) the symptomatic infection and AIDS stage with progressive destruction of the lymph nodes, opportunistic infections and development of neuropathogenesis, and (4) finally, during highly active antiretroviral therapy and in vaccination approaches.