1887

Abstract

Plasma levels of high-mobility group box 1 protein (HMGB1) are elevated during the course of human immunodeficiency virus type 1 (HIV-1) infection and the molecule has an impact on virus replication. This study investigated the mode of cell death and release of HMGB1 during HIV-1 infection . MT4 cells and primary CD4 T cells were infected with HIV-1 isolates, and HMGB1 release was monitored in relation to cytopathic effects (CPE) and apoptosis. HMGB1 release from cells was analysed by Western blotting. For MT4 cells, an enzyme-linked immunosorbent spot (ELISPOT) assay was adapted to measure the release during necrosis. Lactate dehydrogenase (LDH) activity was quantified using a commercial assay. Flow cytometry was used to determine the level of infection and apoptosis. MT4 cells were ≥90 % infected at 48 h post-infection (p.i.). CPE was first observed at 60 h and correlated with release of HMGB1, LDH activity and caspase-3 (C3) activation. HMGB1 spots were clearly detected by ELISPOT assay at 72 h p.i. Annexin V and C3 staining showed that apoptosis was substantially involved in HIV-1-related cell death. Addition of Z-VAD (a caspase inhibitor) in a single dose at 24 or 40 h p.i. decreased both the number of caspase-positive cells and the release of HMGB1. Infection of primary CD4 T cells showed a 22 % (median) infection rate at 96 h. Related CPE corresponded to LDH and HMGB1 release. Both necrosis and apoptosis contributed to HMGB1 liberation during HIV-1-induced cell death and the protein could induce tumour necrosis factor- release from peripheral mononuclear blood cells. These data imply that passive HMGB1 release contributes to the excessive immune activation characteristic of HIV-1 pathogenesis.

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2010-07-01
2019-12-06
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References

  1. Abdurahman, S., Youssefi, M., Höglund, S. & Vahlne, A. ( 2007; ). Characterization of the invariable residue 51 mutations of human immunodeficiency virus type 1 capsid protein on in vitro CA assembly and infectivity. Retrovirology 4, 69 [CrossRef]
    [Google Scholar]
  2. Alleva, L. M., Yang, H., Tracey, K. J. & Clark, I. A. ( 2005; ). High mobility group box 1 (HMGB1) protein: possible amplification signal in the pathogenesis of falciparum malaria. Trans R Soc Trop Med Hyg 99, 171–174.[CrossRef]
    [Google Scholar]
  3. Alleva, L. M., Budd, A. C. & Clark, I. A. ( 2008; ). Systemic release of high mobility group box 1 protein during severe murine influenza. J Immunol 181, 1454–1459.[CrossRef]
    [Google Scholar]
  4. Bell, C. W., Jiang, W., Reich, C. F., III & Pisetsky, D. S. ( 2006; ). The extracellular release of HMGB1 during apoptotic cell death. Am J Physiol Cell Physiol 291, C1318–C1325.[CrossRef]
    [Google Scholar]
  5. Bianchi, M. E. ( 2009; ). HMGB1 loves company. J Leukoc Biol 86, 573–576.[CrossRef]
    [Google Scholar]
  6. Bolton, D. L., Hahn, B. I., Park, E. A., Lehnhoff, L. L., Hornung, F. & Lenardo, M. J. ( 2002; ). Death of CD4+ T-cell lines caused by human immunodeficiency virus type 1 does not depend on caspases or apoptosis. J Virol 76, 5094–5107.[CrossRef]
    [Google Scholar]
  7. Bonaldi, T., Talamo, F., Scaffidi, P., Ferrera, D., Porto, A., Bachi, A., Rubartelli, A., Agresti, A. & Bianchi, M. E. ( 2003; ). Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion. EMBO J 22, 5551–5560.[CrossRef]
    [Google Scholar]
  8. Brenchley, J. M., Price, D. A., Schacker, T. W., Asher, T. E., Silvestri, G., Rao, S., Kazzaz, Z., Bornstein, E., Lambotte, O. & other authors ( 2006; ). Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 12, 1365–1371.
    [Google Scholar]
  9. Cassetta, L., Fortunato, O., Adduce, L., Rizzi, C., Hering, J., Rovere-Querini, P., Bianchi, M. E., Alfano, M. & Poli, G. ( 2009; ). Extracellular high mobility group box-1 inhibits R5 and X4 HIV-1 strains replication in mononuclear phagocytes without induction of chemokines and cytokines. AIDS 23, 567–577.[CrossRef]
    [Google Scholar]
  10. Chen, L. C., Yeh, T. M., Wu, H. N., Lin, Y. Y. & Shyu, H. W. ( 2008; ). Dengue virus infection induces passive release of high mobility group box 1 protein by epithelial cells. J Infect 56, 143–150.[CrossRef]
    [Google Scholar]
  11. Chu, J. J. & Ng, M. L. ( 2003; ). The mechanism of cell death during West Nile virus infection is dependent on initial infectious dose. J Gen Virol 84, 3305–3314.[CrossRef]
    [Google Scholar]
  12. Douek, D. C., Roederer, M. & Koup, R. A. ( 2009; ). Emerging concepts in the immunopathogenesis of AIDS. Annu Rev Med 60, 471–484.[CrossRef]
    [Google Scholar]
  13. Dumitriu, I. E., Baruah, P., Manfredi, A. A., Bianchi, M. E. & Rovere-Querini, P. ( 2005; ). HMGB1: guiding immunity from within. Trends Immunol 26, 381–387.[CrossRef]
    [Google Scholar]
  14. Gaillard, C., Borde, C., Gozlan, J., Marechal, V. & Strauss, F. ( 2008; ). A high-sensitivity method for detection and measurement of HMGB1 protein concentration by high-affinity binding to DNA hemicatenanes. PLoS One 3, e2855 [CrossRef]
    [Google Scholar]
  15. Gougeon, M. L. ( 2003; ). Apoptosis as an HIV strategy to escape immune attack. Nat Rev Immunol 3, 392–404.[CrossRef]
    [Google Scholar]
  16. Harris, H. E. & Raucci, A. ( 2006; ). Alarmin(g) news about danger: workshop on innate danger signals and HMGB1. EMBO Rep 7, 774–778.
    [Google Scholar]
  17. Hunt, P. W. ( 2007; ). Role of immune activation in HIV pathogenesis. Curr HIV/AIDS Rep 4, 42–47.[CrossRef]
    [Google Scholar]
  18. Kosai, K., Seki, M., Yanagihara, K., Nakamura, S., Kurihara, S., Izumikawa, K., Kakeya, H., Yamamoto, Y., Tashiro, T. & Kohno, S. ( 2008; ). Elevated levels of high mobility group box chromosomal protein-1 (HMGB-1) in sera from patients with severe bacterial pneumonia coinfected with influenza virus. Scand J Infect Dis 40, 338–342.[CrossRef]
    [Google Scholar]
  19. Lotze, M. T. & Tracey, K. J. ( 2005; ). High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nat Rev Immunol 5, 331–342.[CrossRef]
    [Google Scholar]
  20. Moanna, A., Dunham, R., Paiardini, M. & Silvestri, G. ( 2005; ). CD4+ T-cell depletion in HIV infection: killed by friendly fire? Curr HIV/AIDS Rep 2, 16–23.[CrossRef]
    [Google Scholar]
  21. Nowak, P., Barqasho, B., Treutiger, C. J., Harris, H. E., Tracey, K. J., Andersson, J. & Sonnerborg, A. ( 2006; ). HMGB1 activates replication of latent HIV-1 in a monocytic cell-line, but inhibits HIV-1 replication in primary macrophages. Cytokine 34, 17–23.[CrossRef]
    [Google Scholar]
  22. Nowak, P., Barqasho, B. & Sonnerborg, A. ( 2007; ). Elevated plasma levels of high mobility group box protein 1 in patients with HIV-1 infection. AIDS 21, 869–871.[CrossRef]
    [Google Scholar]
  23. Park, J. S., Svetkauskaite, D., He, Q., Kim, J. Y., Strassheim, D., Ishizaka, A. & Abraham, E. ( 2004; ). Involvement of Toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein. J Biol Chem 279, 7370–7377.[CrossRef]
    [Google Scholar]
  24. Plymale, D. R., Tang, D. S., Comardelle, A. M., Fermin, C. D., Lewis, D. E. & Garry, R. F. ( 1999; ). Both necrosis and apoptosis contribute to HIV-1-induced killing of CD4 cells. AIDS 13, 1827–1839.[CrossRef]
    [Google Scholar]
  25. Qin, S., Wang, H., Yuan, R., Li, H., Ochani, M., Ochani, K., Rosas-Ballina, M., Czura, C. J., Huston, J. M. & other authors ( 2006; ). Role of HMGB1 in apoptosis-mediated sepsis lethality. J Exp Med 203, 1637–1642.[CrossRef]
    [Google Scholar]
  26. Scaffidi, P., Misteli, T. & Bianchi, M. E. ( 2002; ). Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 418, 191–195.[CrossRef]
    [Google Scholar]
  27. Semino, C., Angelini, G., Poggi, A. & Rubartelli, A. ( 2005; ). NK/iDC interaction results in IL-18 secretion by DCs at the synaptic cleft followed by NK cell activation and release of the DC maturation factor HMGB1. Blood 106, 609–616.[CrossRef]
    [Google Scholar]
  28. Thierry, S., Gozlan, J., Jaulmes, A., Boniface, R., Nasreddine, N., Strauss, F. & Marechal, V. ( 2007; ). High-mobility group box 1 protein induces HIV-1 expression from persistently infected cells. AIDS 21, 283–292.[CrossRef]
    [Google Scholar]
  29. Urbonaviciute, V., Meister, S., Munoz, L., Heyder, P., De Marchis, F., Bianchi, M. E., Kirschning, C., Wagner, H., Manfredi, A. A. & other authors ( 2008; ). Induction of inflammatory and immune response by HMGB1–nucleosome complexes: implications for the pathogenesis of SLE. J Exp Med 205, 3007–3018.[CrossRef]
    [Google Scholar]
  30. Varbanov, M., Espert, L. & Biard-Piechaczyk, M. ( 2006; ). Mechanisms of CD4 T-cell depletion triggered by HIV-1 viral proteins. AIDS Rev 8, 221–236.
    [Google Scholar]
  31. Wahamaa, H., Vallerskog, T., Qin, S., Lunderius, C., LaRosa, G., Andersson, U. & Harris, H. E. ( 2007; ). HMGB1-secreting capacity of multiple cell lineages revealed by a novel HMGB1 ELISPOT assay. J Leukoc Biol 81, 129–136.
    [Google Scholar]
  32. Wang, H., Bloom, O., Zhang, M., Vishnubhakat, J. M., Ombrellino, M., Che, J., Frazier, A., Yang, H., Ivanova, S. & other authors ( 1999; ). HMG-1 as a late mediator of endotoxin lethality in mice. Science 285, 248–251.[CrossRef]
    [Google Scholar]
  33. Wang, H., Ward, M. F., Fan, X. G., Sama, A. E. & Li, W. ( 2006; ). Potential role of high mobility group box 1 in viral infectious diseases. Viral Immunol 19, 3–9.[CrossRef]
    [Google Scholar]
  34. Yasuda, T., Ueda, T., Takeyama, Y., Shinzeki, M., Sawa, H., Nakajima, T., Ajiki, T., Fujino, Y., Suzuki, Y. & Kuroda, Y. ( 2006; ). Significant increase of serum high-mobility group box chromosomal protein 1 levels in patients with severe acute pancreatitis. Pancreas 33, 359–363.[CrossRef]
    [Google Scholar]
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