Читать книгу Immunology - Richard Coico - Страница 101

Complement plays a role in defense against viral infection (see Figure 4.7D). C1 can bind directly to and become activated by the surface of several viruses, including the type C retroviruses, lentiviruses, HIV‐1, and HTLV‐1. In addition, MBL of the lectin pathway binds to and is activated by mannose residues on the surfaces of HIV‐1, HIV‐2, and influenza virus. Antibodies generated in the response against these viruses mediate further binding and activation of the classical pathway on the surface of the virus. Repeating subunits on the viral capsid or membrane surfaces activate the alternative pathway. Binding of complement proteins leads to opsonization and lysis of the virus by phagocytic cells. Complement binding also interferes with the ability of the virus to interact with the membrane of its target cells and thus blocks viral entry into the cell.

Many viruses subvert the immune response by synthesizing proteins that bind to molecules in antigen‐processing pathways (see Chapter 8). Viruses also use mechanisms that undermine the action of complement proteins. For example, some viruses produce proteins that mimic complement inhibitor function: the herpes viruses make proteins that have DAF‐like and/or MCP‐like activities and others that block C5b‐9 formation. In addition, vaccinia virus produces a protein that binds to C3b and C4b and inhibits complement activation. The protein has both decay‐accelerating activity and acts as a co‐factor for factor I. HIV‐1, HTLV‐1, simian immunodeficiency virus (SIV), and cytomegalovirus (CMV) capture the complement control proteins DAF, MCP, and CD59 when the virions bud from host cell membranes. As a consequence of these strategies, the viruses are protected from complement‐mediated responses.

Some viruses even use complement components to promote infection, for example by binding to complement receptors and gaining entry into cells. One of the most studied interactions is the Epstein–Barr virus infection of human B lymphocytes. The virus’s membrane glycoprotein, gp350/220, binds to CR2 (CD21) expressed on the B‐cell surface, allowing the virus to be taken into the cell. Some viruses activate complement and use the C3b deposited on them to bind to host cell complement receptors; in this way, HIV‐1 uses CR1, CR2, and CR3 to infect T cells, B cells, and monocytes. Other viruses bind to membrane‐expressed complement regulators: paramyxovirus (measles virus) uses MCP and viruses of the picornavirus family use DAF to infect epithelial cells.