title: Growth failure and AIDS-like cachexia syndrome in HIV-1 transgenic mice.
abstract: The mechanisms which predispose to growth failure in infants and children infected with immunodeficiency virus type-1 (HIV-1) are not fully understood. The contributions of viral replication and CD4+ T cell depletion to growth failure in an HIV-1 transgenic mouse model were investigated. Mice homozygous for the transgene, a gag-pol deletion mutant of the HIV-1 provirus pNL4-3, exhibited marked cachexia, growth retardation, lymphoproliferation with a reduction in the percentage of CD4+ T cells but an increase in the absolute number of splenic CD4+ and CD8+ T cells, thymic hypoplasia, and early death. Despite the absence of T cells, athymic nude mice, homozygous for the HIV transgene, displayed comparable growth failure. The results indicate that AIDS-like cachexia may be produced by expression of viral envelope or accessory genes, need not be accompanied by absolute depletion of CD4+ T cells, and may occur independent of T cell function.
authors.affiliation: Department of Medicine, University of Colorado Health Sciences Center, Denver 80220.
authors.forename: T J
authors.initials: TJ
authors.lastname: Santoro
authors.forename: J L
authors.initials: JL
authors.lastname: Bryant
authors.forename: J
authors.initials: J
authors.lastname: Pellicoro
authors.forename: M E
authors.initials: ME
authors.lastname: Klotman
authors.forename: J B
authors.initials: JB
authors.lastname: Kopp
authors.forename: L A
authors.initials: LA
authors.lastname: Bruggeman
authors.forename: R R
authors.initials: RR
authors.lastname: Franks
authors.forename: A L
authors.initials: AL
authors.lastname: Notkins
authors.forename: P E
authors.initials: PE
authors.lastname: Klotman
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000382:microbiology* / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002100:Cachexia / Q000276:immunology / Q000382:microbiology* / Q000503:physiopathology; D005260:Female; D015685:Fusion Proteins, gag-pol / Q000235:genetics; D015870:Gene Expression; D015693:Gene Products, nef / Q000032:analysis; D005814:Genes, Viral; D015497:HIV-1 / Q000235:genetics*; D006720:Homozygote; D016130:Immunophenotyping; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D012367:RNA, Viral / Q000032:analysis; D054311:nef Gene Products, Human Immunodeficiency Virus
chemical_list: D015685:Fusion Proteins, gag-pol; D015693:Gene Products, nef; D012367:RNA, Viral; D054311:nef Gene Products, Human Immunodeficiency Virus