Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, North Carolina, USA

Correspondence to: T M Ross, East Carolina University, Brody School of Medicine, Department of Microbiology & Immunology, Brody Health Sciences Building, 600 Moye Boulevard, Greenville, NC 27858-4354, USA; Fax: (252) 816-3104

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. Leukemia (2001) 15, 332-341.

HIV; AIDS; T cell depletion; apoptosis