Complement in Different Stages of HIV Infection and Pathogenesis

Abstract

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.

A functional complement system is required for normal T helper cell differentiation

“…Nevertheless, intracellular pathogens are susceptible to complement during extracellular stages of infection, and there are several examples of complement evasion by such pathogens. For example, several viruses, such as HSV and HIV, protect themselves by binding host complement inhibitors on their surface (Speth et al 2003;Lubinski et al 2002). Intracellular bacteria, e.g.…”

Exploring the Potential of Monoclonal Antibody Therapeutics for HIV-1 Eradication

“…Binding of the antibody Fc to these complement pathway components may trigger the rapid recruitment and activation of complement resulting in the formation of the membrane attack complex and lysis or phagocytosis of the antibody-opsonized cell/virus. [96][97][98][99][100] Because of the abundance of complement activating C1q and MBL in tissues and the circulation, where they induce phagocytic clearance or cytotoxicity, respectively, CDC has been exploited broadly by the oncology-targeting monoclonal therapeutic community. [101][102][103] Thus, CDC activity therapeutics represent a unique and broad acting targeted effector function that may drive rapid clearance of reactivated cells in multiple tissue compartments.…”

Complement and HIV-I infection/HIV-associated neurocognitive disorders

“…For CR-positive but CD4 and chemokine receptor-negative cells like B cells and erythrocytes, HIV-1 can only attach to their surface via CRs but cannot productively infect these cells, which can lead to further trafficking of the virus to other tissues and permissive cells. But cells positive for both CRs and CD4 such as CD4+ T cells, will be infected directly (Speth et al, 2003). Several lines of independent evidence indicate that CD4-gp120, C3d-CR2, iC3b-CR3 and gp41-CD3 interactions may facilitate viral transmission and replication (Lund et al, 1995) (June et al, 1991; Reisinger et al, 1990).…”

“…Indeed, HIV-1 virions from infected individuals accumulate C3 on their surface, an indication of complement activation, but HIV-1 virions have long been recognized to be very resistant to lysis by complement attack (Figure 2) (Stoiber et al, 2008a). Interestingly, all other mammalian RNA viruses tested thus far can be inactivated by complement-mediated lysis using human serum (Speth et al, 2003). Furthermore, opsonization of HIV-1 with C3 enhances its infectivity by facilitating the interaction of HIV-1 viral particles with complement-receptor-positive cells such as monocytes/macrophage and dendritic cells (Stoiber et al, 2001).…”