title: Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV- and SIV-infected lymph nodes.
abstract: Although 13 years have passed since identification of human immunodeficiency virus-1 (HIV-1) as the cause of AIDS, we do not yet know how HIV kills its primary target, the T cell that carries the CD4 antigen. We and others have shown an increase in the percentage of apoptotic cells among circulating CD4+ (and CD8+) T cells of HIV-seropositive individuals and an increase in frequency of apoptosis with disease progression. However, it is not known if this apoptosis occurs in infected or uninfected T cells. We show here, using in situ labelling of lymph nodes from HIV-infected children and SIV-infected macaques, that apoptosis occurs predominantly in bystander cells and not in the productively infected cells themselves. These data have implications for pathogenesis and therapy, namely, arguing that rational drug therapy may involve combination agents targeting viral replication in infected cells and apoptosis of uninfected cells.
authors.affiliation: Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA.
authors.forename: T H
authors.initials: TH
authors.lastname: Finkel
authors.forename: G
authors.initials: G
authors.lastname: Tudor-Williams
authors.forename: N K
authors.initials: NK
authors.lastname: Banda
authors.forename: M F
authors.initials: MF
authors.lastname: Cotton
authors.forename: T
authors.initials: T
authors.lastname: Curiel
authors.forename: C
authors.initials: C
authors.lastname: Monks
authors.forename: T W
authors.initials: TW
authors.lastname: Baba
authors.forename: R M
authors.initials: RM
authors.lastname: Ruprecht
authors.forename: A
authors.initials: A
authors.lastname: Kupfer
mesh_terms: D000818:Animals; D017209:Apoptosis; D002648:Child; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections / Q000473:pathology / Q000821:virology*; D015497:HIV-1 / Q000472:pathogenicity; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology* / Q000821:virology; D008251:Macaca; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000473:pathology / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000821:virology
chemical_list: D012333:RNA, Messenger; D012367:RNA, Viral