Tumor necrosis factor-alpha stimulates HIV-1 production in primary culture of human adipocytes.
Adipose tissue of HIV-1-infected patients shows severe abnormalities such as profound changes in adipose tissue morphology and metabolism. Does HIV-1 infect the adipose cell remains an unsolved question since previous attempts showed that HIV-1 poorly infects human adipocytes in vitro. In the present study, preadipose cells from human subcutaneous fat pads were differentiated in vitro, checked for HIV receptor expression, then infected with R5 and X4 HIV1 strains. Using a sensitive RT-PCR assay, we showed that HIV-1 tat and rev early viral transcripts were expressed in infected adipocytes giving a clear evidence of HIV-1 transcriptional activity in these cells. However, at the same time, no sign of productive infection was demonstrated since infected adipocytes did not efficiently produce Gag p24 antigen. We hypothesized that such a limitation could result from the lack of activation of adipocyte-signaling pathways able to stimulate HIV-1 gene expression in quiescent adipocytes. Indeed, a significant increase in Gag p24 production was observed after stimulation of infected adipocytes with pro-inflammatory cytokines, such as tumor necrosis factor alpha or interleukin-1-beta. Taken together, these results demonstrate that HIV-1 does infect human adipose cells in vitro and suggest that the initial limited infection can be overcome upon pro-inflammatory cytokine treatment.
Maurin
T
T
U526-Laboratoire de Virologie, Faculté de Médecine, Av. de Valombrose, 06107- NICE cedex 2, France.
Saillan-Barreau
C
C
Cousin
B
B
Casteilla
L
L
Doglio
A
A
Pénicaud
L
L
D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism / Q000821:virology*; D002478:Cells, Cultured; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000502:physiology; D015694:Gene Products, rev / Q000235:genetics / Q000378:metabolism; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism; D016655:HIV Core Protein p24 / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D039682:HIV-Associated Lipodystrophy Syndrome / Q000378:metabolism / Q000821:virology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects* / Q000502:physiology; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus
D015694:Gene Products, rev; D015696:Gene Products, tat; D016655:HIV Core Protein p24; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus