Growth failure and AIDS-like cachexia syndrome in HIV-1 transgenic mice.
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.
Santoro
T J
TJ
Department of Medicine, University of Colorado Health Sciences Center, Denver 80220.
Bryant
J L
JL
Pellicoro
J
J
Klotman
M E
ME
Kopp
J B
JB
Bruggeman
L A
LA
Franks
R R
RR
Notkins
A L
AL
Klotman
P E
PE
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
D015685:Fusion Proteins, gag-pol; D015693:Gene Products, nef; D012367:RNA, Viral; D054311:nef Gene Products, Human Immunodeficiency Virus