Autophagy: an overlooked mechanism of HIV-1 pathogenesis and neuroAIDS?
Human immunodeficiency virus type 1 (HIV-1) establishes a persistent infection characterized by progressive depletion of CD4(+) lymphocytes and immunosuppression. Although extensive research has examined the importance of apoptosis as a cause of cell death associated with HIV-1 infection, the role of autophagy has been largely ignored. Our laboratory has examined the autophagic process in HIV-1-infected cells. Following infection of human peripheral blood CD4(+) T-cells or U937 cells with HIV-1 for 48 hours, the autophagy proteins Beclin 1 and LC3-II were found to be markedly decreased. Beclin 1 mRNA expression and autophagosomes were also reduced in HIV-1 infected cells. Thus, our data indicate that HIV-1 infection inhibits autophagy in infected cells in contrast to the previously described induction of autophagy by gp120 in uninfected bystander cells. It is likely that HIV-1 has evolved this mechanism as part of an elaborate attempt to evade the immune system while promoting its own replication. We believe that autophagy is an overlooked mechanism in HIV-1 pathogenesis and plays a particularly important role in the early cognitive impairment and dementia often associated with advanced AIDS. A model is presented that describes the potential role of autophagy in NeuroAIDS.
Spector
Stephen A
SA
Department of Pediatrics, Division of Infectious Diseases, University of California, San Diego, La Jolla, California 92093-0672, USA. saspector@ucsd.edu
Zhou
Dejiang
D
D015526:AIDS Dementia Complex / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D015699:HIV Envelope Protein gp120 / Q000502:physiology; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D020298:U937 Cells
D015699:HIV Envelope Protein gp120