HIV-1 triggers apoptosis in primary osteoblasts and HOBIT cells through TNFα activation

Several HIV-1 infected patients show bone loss and osteopenia/osteoporosis during the course of disease. The mechanisms underlying this degenerative process are largely unsettled and it has not been determined yet whether bone dysfunction is linked to HIV-1-mediated direct and/or indirect effects on...

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Bibliographic Details
Published in:Journal of medical virology 2008-09, Vol.80 (9), p.1507-1514
Main Authors: Gibellini, Davide, De Crignis, Elisa, Ponti, Cristina, Cimatti, Laura, Borderi, Marco, Tschon, Matilde, Giardino, Roberto, Re, Maria Carla
Format: Article
Language:English
Subjects:
apoptosis
Biological and medical sciences
Fundamental and applied biological sciences. Psychology
HIV-1
Human immunodeficiency virus 1
Human viral diseases
Infectious diseases
Medical sciences
Microbiology
Miscellaneous
osteoblasts
TNFα
Viral diseases
Virology
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Summary:Several HIV-1 infected patients show bone loss and osteopenia/osteoporosis during the course of disease. The mechanisms underlying this degenerative process are largely unsettled and it has not been determined yet whether bone dysfunction is linked to HIV-1-mediated direct and/or indirect effects on osteoblasts/osteoclasts cross-talk regulation. This study investigated the effects of HIV-1IIIb and HIV-1ADA strains on osteoblasts using the osteoblast-derived cell line (HOBIT) and primary human osteoblasts as cellular models. The challenge of these cell cultures by both HIV-1 strains triggered a significant apoptosis activation unrelated to viral infection, since proviral HIV-1 DNA and supernatant HIV-1 RNA were not detected by real time PCR or b-DNA assays respectively. Under the experimental conditions, even heat-inactivated HIV-1 or cross-linked recombinant gp120 treatment of HOBIT and osteoblasts induced programmed cell death, suggesting that apoptosis is regulated by the interaction between HIV-1 gp120 and cell membrane. The analysis of cell culture supernatants showed a significant up-regulation of TNFα, a pleiotropic protein considered an apoptosis inducer in the osteoblast model. In fact, pretreatment of HOBIT and osteoblast cell cultures with anti-TNFα polyclonal antibody tackled effectively HIV-1 related induction of cell apoptosis. As a whole, these results indicate that HIV-1 may impair bone mass structure homeostasis by TNFα regulated osteoblast apoptosis. J. Med. Virol. 80:1507-1514, 2008.
ISSN:0146-6615
1096-9071
DOI:10.1002/jmv.21266