Infection by human immunodeficiency virus (HIV) is associated with an early immune dysfunction and progressive destruction of CD4+ T lymphocytes. This progressive disappearance of T cells leads to a lack of immune control of HIV replication and to the development of immune deficiency resulting in the increased occurrence of
opportunistic infections associated with
acquired immune deficiency syndrome (
AIDS). The HIV-induced, premature destruction of lymphocytes is associated with the continuous production of HIV
viral proteins that modulate apoptotic pathways. The
viral proteins, such as Tat, Env, and Nef, are associated with chronic immune activation and the continuous induction of apoptotic factors.
Viral protein expression predisposes lymphocytes, particularly CD4+ T cells, CD8+ T cells, and antigen-presenting cells, to evolve into effectors of apoptosis and as a result, to lead to the destruction of healthy, non-infected T cells. Tat and Nef, along with Vpu, can also protect HIV-infected cells from apoptosis by increasing
anti-apoptotic proteins and down-regulating
cell surface receptors recognized by immune system cells. This review will discuss the validity of the apoptosis hypothesis in HIV disease and the potential mechanism(s) that
HIV proteins perform in the progressive T cell depletion observed in
AIDS pathogenesis.