Modulation of accessory cell function and interleukin-6 production by the HIV-1 tat gene.
Manifestations of HIV-1 infection such as fever, hypergammaglobulinemia, and interstitial pneumonitis may be due to increased production of inflammatory cytokines such as interleukin-1 and interleukin-6 (IL-6). Monocytes/macrophages of HIV-1-infected individuals have been noted to produce increased amounts of IL-6, as well as to have enhanced accessory cell function. These studies examined the ability of HIV-1 tat, an important HIV-1 regulatory gene, to modulate monocyte/macrophage function. In these experiments, HIV-1 tat-transfected THP-1 cells, a monocytic cell line, enhanced THP-1 immune accessory cell function in the presence of pokeweed mitogen and concanavalin A. HIV-1 tat-transfected cells also increased production of lipopolysaccharide-stimulated IL-6 mRNA and IL-6 protein. The ability of monocytes/macrophages to support HIV-1 production while exhibiting little or no cytopathic effects allows these cells to serve as a reservoir for the virus. The ability of HIV-1 tat to regulate cellular function in monocytes/macrophages may play an important part in the pathogenesis of HIV-1 infection.
Iwamoto
G K
GK
Department of Medicine, Indiana University School of Medicine, Indianapolis.
Konicek
S A
SA
Twigg
H L
HL
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D002460:Cell Line; D015696:Gene Products, tat / Q000235:genetics*; D005814:Genes, Viral; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D014162:Transfection; D014779:Virus Replication / Q000235:genetics; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D015850:Interleukin-6; D012333:RNA, Messenger; D054322:tat Gene Products, Human Immunodeficiency Virus