AIDS pathogenesis: the role of accessory gene mutations, leading to formation of long-lived persistently infected cells and/or apoptosis-inducing HIV-1 particles.
Human immunodeficiency virus type 1 (HIV-1) infection indirectly induces activation-dependent apoptosis in bystander immune CD4+ T-cells, a hallmark of AIDS pathogenesis. It is well known that this pathogenetic event is significantly correlated with a high virus load. Active viral replication occurs in HIV-1 asymptomatic carriers throughout all stages of clinical disease. Most of the HIV-1 in plasma is derived from short-lived infected cells with a half life of a few days; however, a minor population of virus is derived from long-lived persistently and latently infected cells. Recently, the importance of such latent reservoirs for HIV-1 has come to the forefront because of studies with potent antiretroviral inhibitors that block only new rounds of infection. An initial large drop in viral load occurs within two weeks as noted by a decrease in plasma viremia. This is then followed by a slower second-phase decay, since only a small fraction of latently infected resting CD4+ T-cells carry replication-competent, integrated provirus. This review highlights the mechanisms of apoptosis induction in bystander immune cells by both protease-defective, gp120-containing HIV-1 particles, as well as by wild-type virus that appears to be derived predominantly from long-lived infected cells. A model involving the NH2-terminal Nef domain (p7) in this 'bystander apoptosis' event is also presented.
Ikuta
K
K
Section of Serology, Institute of Immunological Science, Hokkaido University, Sapporo, Japan. ki@imm.hokudai.ac.jp
Kameoka
M
M
Luftig
R B
RB
D000163:Acquired Immunodeficiency Syndrome / Q000503:physiopathology* / Q000821:virology; D017209:Apoptosis; D002213:Capsid / Q000378:metabolism; D036022:Capsid Proteins; D015683:Gene Products, gag / Q000378:metabolism; D015693:Gene Products, nef / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009154:Mutation; D013997:Time Factors; D014764:Viral Proteins; D014771:Virion; D016662:Virus Integration; D017735:Virus Latency; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus
D036022:Capsid Proteins; D015683:Gene Products, gag; D015693:Gene Products, nef; C071884:NCP7 protein, Human immunodeficiency virus 1; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus