Escafe from immune control by HIV
McMichael A., Goulder P., Rowland-Jones S., Phillips R., Xu O., Screaton G.
There is good evidence thai cytotoxic I' lymphocytes play an important role in controlling the initial viremia oï HIV infection. Thereafter, a balance is established between virus load and the level of the cellular immune response. In other virus infections, such as EBV, control is maintained throughout the life of the infected person However, for HIV; the immune response ultimately breaks down, but at a variable rate. Escape from immune control occurs al all phases of the infection. Selection of virus mutants, in which dominant epitopes recognised by cytotoxic T lymph(x:ytes (CTL) have been described early in infection, in the middle phase, and as patients progress to AIDS. It is possible that such mutations are common, causing a broadening of the CTL response in terms of epitopes recognized, but at the cost of an increasing virus load as the response focuses on less dominant epitopes. Another mechanism by which C I"L can escape from immune control, is a reverse attack bv the HIV-infected target cells. Our experiments have shown that both HIV and SIV up-regulate expression of Fas Ligand (Fas L) in infected cells and that these cells can lyse T lymphocytes expressing Fas. The latter include CTL which may be particularly susceptible because of their contact with infected cells through the T cell antigen receptor. The nef protein is important in up regulation of Fas Ligand and some mutant viruses with altered nef sequence or deletions fail to up-regular Fas Ligand. Together these mechanisms provide a potent escape route for HIV from immune control. As virus load increases and CD4> cells are lost more rapidly, there will be direct impairment of immune responses because of destruction of key cellular components. Thus, in late infection the failure of immune control becomes catastrophic.