The Immunopathogenesis of Human Immunodeficiency Virus Infection

TLDR

HIV infection initiates by gp120 binding CD4 on T cells and mononuclear phagocytes, followed by gp41‑mediated fusion, reverse transcription, and integration, leading to active replication or latency modulated by cytokines and other factors, ultimately causing AIDS. Recent studies emphasize that LFA‑1 adhesion molecules facilitate HIV entry, and that CD4+ T cells constitute the main reservoir in blood and lymphoid tissues, while mononuclear phagocytes sustain infection in non‑lymphoid organs such as brain and lung.

Abstract

Infection with human immunodeficiency virus (HIV) causes AIDS. As a consequence of the interaction of gp120 envelope with the CD4 receptor molecule expressed by a subset of T lymphocytes and by mononuclear phagocytes (MPs), a second envelope protein (gp41) mediates fusion of the virion membrane with the target membrane. In these events the role of adhesion molecules such as LFA-1 has recently been highlighted. Following viral entry, reverse transcription of the virion-associated RNA and integration of proviral DNA into the host genome are crucial steps in HIV infection, which can lead to expression of high levels of new HIV or to silent infection for indefinite periods, a condition defined as viral latency. Several factors in addition to endogenous viral regulatory proteins have been reported as capable of modulating the state of viral latency and expression in vitro, including the cytokine network that normally modulates immune homeostasis as well as the immune response to inflammatory stimuli. Finally, recent studies have underscored the observation that the CD4+ T lymphocytes are the major reservoir of HIV in the peripheral blood compartment and in the lymphoid tissues, which are characterized by a greater viral burden, whereas in nonlymphoid organs such as the brain and the lung, local infection is predominantly sustained by MPs.