Induction of HIV-1 expression in chronically infected promonocytic cells cocultured with human lung fibroblasts.
The interaction between a chronically human immunodeficiency virus type 1 (HIV-1)-infected promonocytic line (U1) and a normal human embryonic lung fibroblast line (MRC-5) on HIV-1 expression was investigated. Coculture of U1 cells with MRC-5 cells induced HIV-1 reverse transcriptase (RT) activities 40- to 50-fold higher than those of parallel control cultures of U1 cells. Culture of U1 cells in the presence of media conditioned by MRC-5 cell culture supernatants resulted in a 30- to 40-fold greater HIV-1 RT activity over a 6-day period. HIV-1 RT activity, however, was not increased in the chronically infected T lymphocyte cell line (ACH-2) by either coculture with MRC-5 cells or when cultured in the MRC-5 cell culture supernatant-conditioned media. A polyclonal antibody against interleukin-6 (IL-6) blocked HIV-1 induction in the U1 cells by MRC-5 culture supernatants, indicating that IL-6 plays an important role in the HIV-1 induction. The magnitude of HIV-1 induction by the MRC-5 cell culture supernatant-conditioned media was proportional to the concentration of IL-6. In addition, the supernatants from three other normal human lung fibroblast (HLF) cell lines induced HIV-1 RT expression in U1 cells. Thus, normal unstimulated HLFs stimulate HIV-1 expression in chronically infected promonocytic cells by secreting IL-6, suggesting that the interaction of HLFs and macrophages may play an important role in the development of HIV-1 infection in the lungs.
Ho
W Z
WZ
Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Medical School 19104, USA.
Li
Y H
YH
Zhu
X H
XH
Song
L
L
Douglas
S D
SD
D000906:Antibodies / Q000494:pharmacology; D002460:Cell Line; D002474:Cell-Free System / Q000276:immunology; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology; D003587:Cytomegalovirus / Q000502:physiology; D005347:Fibroblasts / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000821:virology*; D006801:Humans; D008168:Lung; D009000:Monocytes / Q000276:immunology / Q000821:virology*; D013601:T-Lymphocytes / Q000821:virology; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000276:immunology*
D000906:Antibodies; D016207:Cytokines